Urine Formation

The primary functions of the nephrons include removing waste substances from the blood and regulating water and electrolyte concentrations within the body fluids. The end product of these functions is urine, which is excreted to the outside of the body, containing wastes, excess water, and excess electrolytes.

Urine formation involves glomerular filtration, tubular reabsorption, and tubular secretion.

Glomerular Filtration

Urine formation begins when water and various dissolved substances are filtered out of the glomerular capillaries and into the glomerular capsules. The filtration of these materials through the capillary walls is much like the filtration that occurs at the arteriole ends of other capillaries throughout the body.

The glomerular capillaries, however, are many times more permeable than the capillaries in other tissues due to the presence of numerous tiny openings (fenestrae) in their walls.

Filtration Pressure
As in case of other capillaries, the main force responsible for moving substances through the glomerular capillary wall is the pressure of the blood inside (glomerular hydrostatic pressure). This movement is also influenced by the osmotic pressure of the plasma in the glomerulus and by the hydrostatic pressure inside the glomerular capsule. An increase in either of these pressures will oppose movement out of the capillary and, thus, reduce filtration. The net pressure acting to force substances out of the glomerulus is called the filtration pressure.

The glomerular filtrate consists of substances that enter the space within the glomerular capsule, and it has about the same composition as the filtrate that becomes tissue fluid elsewhere in the body. That is, glomerular filtrate is largely water and contains essentially the same substances as the blood plasma, except for the larger protein molecules, which the filtrate lacks. The relative concentrations of some of the substances in the plasma, glomerular filtrate, and urine are shown below

Concentration (mEq/l)
Substance Plasma Glom.Filtrate Urine
Sodium 142 142 128
Potassium 5 5 60
Calcium 4 4 5
Magnessium 3 3 15
Chlorine 103 103 134
Bicarbonate 27 27 14
Sulfate 1 1 33
Phospahte 2 2 40
Concentration (mg/100ml)
Substance Plasma Glom. Filtrate Urine
Glucose 100 100 0
Urea 26 26 1820
Uric acid 4 4 53

Filtration Rate
The rate of glomerular filtration is directly proportional to the filtration pressure. Consequently, the factors that affect the glomerular hydrostatic pressure, glomerular plasma osmotic pressure, or hydrostatic pressure in the glomerular capsule will also affect the rate of filtration.
For example, since the glomerular capillary is located between two arterioles - the afferent and efferent arterioles- any change in the diameters of these vessels is likely to cause a change in the glomerular hydrostatic pressure and will be accompanied by a change in the glomerular filtration rate. The afferent arteriole, though which the blood enters the glomerulus, may constrict as a result of mild stimulation by sympathetic nerve impulses. If this occurs, the blood flow diminishes, the glomerular hydrostatic pressure decreases, and the filtration rate drops. If, on the other hand, the efferent arteriole (through which the blood leaves the glomerulus) constricts, the blood backs
up into the glomerulus, the glomerulus, the glomerular hydrostatic pressure increases, and the filtration rate rises. Converse effects are produced by vasodilation of these vessels.

In the capillaries, the blood pressure, acting to force water and dissolved substances outward, is opposed by the effect of the plasma osmotic pressure that attracts water inward. As filtration occurs through the capillary wall, the proteins remaining in the plasma cause the osmotic pressure within the glomerular capillary to rise. When this pressure reaches a certain high level, filtration ceases. Conversely, conditions that tend to decrease plasma osmotic pressure, such as a decrease in plasma protein concentration, cause an increase in the filtration rate.

The hydrostatic pressure in the glomerular capsule sometimes changes as a result of an obstruction, such as may be caused by a stone in a ureter or an enlarged prostate gland pressing on the urethra. If this occurs, fluids tend to back up into the renal tubules and cause the hydrostatic pressure in the glomerular capsules to rise. Since any increase in capsular pressure opposes glomerular filtration, the rate of filtration may decrease significantly.

In an average adult, the glomerular filtration rate for the nephrons of both kidneys is about 125 milliliters per minute, or 180,000 milliliters (180 liters) in 24 hours. Since this 24-hour volume is nearly 45 gallons, it is obvious that not all of it is excreted as urine. Instead, most of the fluid that passes through the renal tubules is re absorbed and reenters the plasma.

Regulation of filtration rate

The regulation of glomerular filtration rate involves the juxtaglomerular apparatus, which was described previously, and two negative feedback mechanisms. These mechanisms are triggered whenever the filtration rate is decreasing. For example, as the rate decreases, the concentration of chloride ions reaching the macula densa in the distal convoluted tubule also decreases. In response, the macula densa signals the smooth muscles in the wall of the afferent arteriole to relax, and the vessel becomes dilated. This action allows more blood to flow into the glomerulus, increasing the glomerular pressure, and as a consequence, the filtration rate rises toward its previous level.

At the same time that the macula densa signals the afferent arteriole to dilate, it stimulates the juxtaglomerular cells to release renin. This enzyme causes a plasma globulin (angiotensinogen) to form a substance called angiotensin I, which is converted quickly to angiotensin II by an enzyme (converting enzyme) present in the lungs and plasma.

Angiotensin II is a vasoconstrictor, and it stimulates the smooth muscle cells in the wall for the efferent arteriole to contract, constricting the vessel. As a result of this action, blood tends to back up into the glomerulus, and as the glomerular hydrostatic pressure increases, the filtration rate also increases.

These two mechanisms operate together to ensure a constant blood flow through the glomerulus and a relatively stable glomerular filtration rate, in spite of marked changes occurring in the arterial blood pressure.

TUBULAR REABSORPTION
If the composition of the glomerular filtrate entering the renal tubule is compared with that of the urine leaving the tubule, it is clear that changes occur as the fluid passes through the tubule. For example, glucose is present in the filtrate, but absent in the urine. Also, urea and uric acid are considerably more concentrated in the urine than they are in the glomerular filtrate. Such changes in fluid composition are largely the result of tubular reabsorption, a process by which substances are transported out of the glomerular filtrate, through the epithelium of the renal tubule, and into the blood of the peritubular capillary.

Since the efferent arteriole is narrower than the peritubular capillary, the blood flowing from the former into the latter is under relatively slow pressure. Also, the wall of this capillary is more permeable than that of other capillaries. Both of these factors enhance the rate of fluid reabsorption from the renal tubule.

Although tubular reabsorption occurs throughout the renal tubule, most of it occurs in the proximal convoluted portion. The epithelial cells in this portion have numerous microscopic projections, called microvilli, that form a "brush border" on their free surfaces. These tiny extensions greatly increase the surface area exposed to the glomerular filtrate and enhance the reabsorption process.

Various segments of the renal tubular are adapted to reabsorb specific substances, using particular modes of transport. Glucose reabsorption, for example, occurs primarily through the wall of the proximal tubule by active transport.

Water also is reabsorbed rapidly though the epithelium of the proximal tubule by osmosis; however, portions of the distal tubule and collecting duct are almost impermeable to water. This characteristic of the distal tubule and collecting duct is important in the regulation of urine concentration and volume.

Active transport depends on the presence of carrier molecules in a cell membrane. These carriers transport passenger molecules through the membrane, release them, and return to the other side to transport more passenger molecules. Such a mechanism has a limited transport capacity; that is, it can only transport a certain number of molecules in a given amount of time, because the number of carriers is limited.

Usually all of the glucose in the glomerular filtrate is reabsorbed, because there are enough carrier molecules to transport it. Sometimes, however, the plasma glucose concentration increases, and if it reaches a critical level, called the renal plasma threshold, there will be more glucose molecules in the filtrate than the active transport mechanism can handle. As a result, some glucose will remain in the filtrate and be excreted in the urine.

Amino acids also enter the glomerular filtrate and are reabsorbed in the proximal convoluted tubule, apparently by three different active transport mechanisms. Each mechanism is though to reabsorb a different group of amino acids, whose members have molecular similarities. As a result of their actions, only a trace of amino acids usually remains in the urine.

Although the glomerular filtrate is nearly free of protein, some albumin may be present. These proteins have relatively small molecules, and they are reabsorbed by pinocytosis through the brush border of the epithelial cells lining the proximal convoluted tubule. Once they are inside an epithelial cell, the proteins are converted to amino acids and moved into the blood of the peritubular capillary.

Other substances reabsorbed by the epithelium of the proximal convoluted tubule include creatine, lactic acid, citric acid, uric acid, ascorbic acid (vitamin C), phosphate ions, sulfate ions, calcium ions, potassium ions, and sodium ions. As a group, these substances are reabsorbed by active transport mechanisms with limited transport capacities. Such a substance usually does not appear in the urine until it concentration in the glomerular filtrate exceeds its particular threshold.

Sodium and Water Reabsorption
Substances that remain in the renal tubule tend to become more and more concentrated as water is reabsorbed from the filtrate. Most water reabsorption occurs passively by osmosis in the proximal convoluted tubule and is closely associated with the active reabsorption of sodium ions. In fact, if sodium reabsorption increase, water reabsorption increase; is sodium reabsorption decreases, water reabsorption decreases also.
About 70 percent of sodium ion reabsorption occurs in the proximal segment of the renal tubule by active transport (the sodium pump mechanism). As these positively charged ions (Na+) are moved though the tubular wall, negatively charged ions including chloride ions (Cl-), phosphate ions (PO4-3), and bicarbonate ions (HCO3-) accompany them. This movement of negatively charged ions is due to the electrochemical attraction between particles of opposite charge. It is termed passive transport because it does no require a direct expenditure of cellular energy. As more and more sodium ions are actively transported into the peritubular capillary, along with various negatively charged ions,
the concentration of solutes within the peritubular blood is increased. Furthermore, since water moves through cell membranes from regions of lesser solute concentration (hypotonic) toward regions of greater solute concentration (hypertonic), water is transported by osmosis from the renal tubule into the peritubular capillary. Because of the movement of solutes and water into the peritubular capillary, the volume of fluid within the renal tubule is greatly reduced.

Regulation of Urine Concentration and Volume
Sodium ions continue to be reabsorbed by active transport as the tubular fluid moves through the loop of the Henle, the distal convoluted segment, and the collective duct. As a result, almost all of the sodium that enters the renal tubule as part of the glomerular filtrate may be reabsorbed before the urine is excreted, and consequently, water also continues to be reabsorbed passively by osmosis in various segments of the renal tubule.

Additional water may be reabsorbed due to the action of aldosterone and antidiuretic hormone (ADH). Aldosterone is secreted by cells of the adrenal cortex in response to changes in the blood concentrations of sodium ions and potassium ions. The effect of aldosterone is to cause sodium ions and water molecules to be conserved, thus reducing urine output.

ADH is produced by neurons in the hypothalamus. It is released from the posterior lobe of the pituitary gland in response to a decreasing concentration of water in the blood. when the ADH reaches the kidney, it causes an increase in the permeability of the epithelial linings of the distal convoluted tubule and collecting duct, and water moves rapidly out of these segments by osmosis. Consequently, the urine volume is reduced, and the urine becomes more concentrated.

Thus ADH stimulates the production of concentrated urine, which contains soluble wastes and other substances in a minimum of water; it also inhibits the loss of body fluids whenever there is a danger of dehydration. If the water concentration of the body is excessive, ADH secretion is decreased. in the absence of ADH, the epithelial linings of the distal segment and collecting duct become less permeable to water, less water is reabsorbed, and the urine tends to be more dilute.

Role of ADH in regulation of urine concentration and volume
1. Concentration of water in blood decreases
2. Osmoreceptors in hypothalamus of brain are stimulated
3. Hypothalamus signals the posterior pituitary gland to relase ADH
4. Blood carries ADH to the kidney
5. ADH causes the distal convoluted tubules and collecting ducts to increase water reabsorption by osmosis
6. Urine becomes more concentrated and urine volume decreases

Urea and Uric Acid Excretion

Urea is a by-product of amino acid catabolism. Consequently, its plasma concentration is directly related to the amount of protein in the diet. Urea enters the renal tubule by filtration and about 50 percent of it is reabsorbed (passively) by diffusion, but the remainder is excreted in the urine.

Uric acid, which results from metabolism of certain organic bases in nucleic acids, is reabsorbed by active transport. Although this mechanism seems able to reabsorb all the uric acid normally present in glomerular filtrate, about 10 percent of this amount filtered is excreted in the urine. This amount is apparently secreted into the renal tubule.

Tubular Secretion

Tubular secretion is process by which certain substances are transported from the plasma of the peritubular capillary into the fluid of the renal tubule. As a result, the amount of particular substance excreted into the urine may be greater than the amount filtered from the plasma in the glomerulus.

Some substances are secreted by active transport mechanisms similar to those that function in reabsorption. Secretory mechanisms, however, transport substances in the opposite direction. For example, certain organic compounds, including penicillin, creatinine, and histamine, are actively secreted into the tubular fluid by the epithelium of the proximal convoluted segment.

Hydrogen ions are also actively secreted. In this case, the proximal segment of the renal tubule is specialized to secrete large quantities of hydrogen ions between the plasma and the tubular fluid, where the hydrogen ions plays an important role in the regulation of the pH of the body fluids.

Although most of the potassium ions in the glomerular filtrate are actively reabsorbed in the proximal convoluted tubule, some may be secreted passively in the distal segment and collecting duct. During this process, the active reabsorption of sodium ions out of the fluid produces a negative electrical charge within the tube. Because the positively charged potassium ions (K+) and hydrogen ions (H+) are attracted to regions that are negatively charged, these ions move through the tubular epithelium and enter the tubular fluid.

Composition of Urine
The composition of urine varies considerably from time to time because of variations in dietary intake and physical activity. In addition to containing about 95 percent water, urine usually contains urea and uric acid. it may also contain a trace of amino acids, as well as a variety of electrolytes, whose concentrations tend to vary directly with the amounts included in the diet.

The volume of urine produced usually varies between 0.6 and 2.5 liters per day. The exact volume is influenced by such factors as fluid intake, environmental temperature, relative humidity of the surrounding air, and the person's emotional condition, respiratory rate, and body temperature. An output of 50 to 60 cc of urine per hour is considered normal, and an output of less than 30 cc per hour may be an indication of kidney failure.

Part Function
Glomerulus Filtration of water and dissolved substances from the plasma
Glomerular capsule Receives glomerular filtrate
Proximal convoluted tubule

Reabsorption of glucose, amino acids, lactic acid, uric acid, creatine, citric acid, ascorbic acid, phosphate, sulfate, calcium, potassium, and sodium ions by active transport

Reabsorption of water by osmosis

Reabsorption of chloride ions and other negatively charged ions by electrochemical attraction

Active secretion of substances such as penicillin, histamine, creatine, and hydrogen ions

Descending limb of Loop of Henle Reabsorption of water
Ascending limb of Loop of Henle Reabsorption of chloride ions by active transport and passive reabsorption of sodium ions
Distal convoluted tubule

Reabsorption of sodium ions by active transport

Reabsorption of water by osmosis

Active secretion of hydrogen ions

Passive secretion of potassium ions by electrochemical attraction