The formation of urine begins in the same manner as the formation of tissue fluid—by filtration of plasma through capillary pores. These capillaries are known as glomeruli, and the filtrate they produce enters a system of tubules that transports and modifies the filtrate (by mechanisms discussed in chapter 17). The kidneys produce about 180 L per day of blood filtrate, but since there is only 5.5 L of blood in the body, it is clear that most of this filtrate must be returned to the vascular system and recycled. Only about 1.5 L of urine is excreted daily; 98% to 99% of the amount filtered is reabsorbed back into the vascular system.
The volume of urine excreted can be varied by changes in the reabsorption of filtrate. If 99% of the filtrate is reabsorbed, for example, 1% must be excreted. Decreasing the reabsorption by only 1%—from 99% to 98%—would double the volume of urine excreted (an increase to 2% of the amount filtered). Carrying the logic further, a doubling of urine volume from, for example, 1 to 2 liters, would result in the loss of an additional liter of blood volume. The percentage of the glomerular filtrate reabsorbed—and thus the urine volume and blood volume—is adjusted according to the needs of the body by the action of specific hormones on the kidneys. Through their effects on the kidneys, and the resulting changes in blood volume, these hormones serve important functions in the regulation of the cardiovascular system.
Regulation by Antidiuretic Hormone (ADH)
One of the major hormones involved in the regulation of blood volume is antidiuretic hormone (ADH), also known as vasopressin. As described in chapter 11, this hormone is produced by neurons in the hypothalamus, transported by axons into the posterior pituitary, and released from this storage gland in response to hypothalamic stimulation. The release of ADH from the posterior pituitary occurs when neurons in the hypothalamus called osmoreceptors detect an increase in plasma osmolality (osmotic pressure).
An increase in plasma osmolality occurs when the plasma becomes more concentrated (chapter 6). This can be produced either by dehydration or by excessive salt intake. Stimulation of osmoreceptors produces sensations of thirst, leading to increased water intake and an increase in the amount of ADH released from the posterior pituitary. Through mechanisms that will be discussed in conjunction with kidney physiology in chapter 17, ADH stimulates water reabsorption from the filtrate. A smaller volume of urine is thus excreted as a result of the action of ADH (fig. 14.11).
A person who is dehydrated or who consumes excessive amounts of salt thus drinks more and urinates less. This raises the blood volume and, in the process, dilutes the plasma to lower its previously elevated osmolality. The rise in blood volume that results from these mechanisms is extremely important in stabilizing the condition of a dehydrated person with low blood volume and pressure.
Posterior Thirst pituitary
Posterior Thirst pituitary t ADH
Water retention '
Water retention '
■ Figure 14.11 The negative feedback control of blood volume and blood osmolality. Thirst and ADH secretion are triggered by a rise in plasma osmolality. Homeostasis is maintained by countermeasures, including drinking and conservation of water by the kidneys.
Remember that Charlie had a low urine output and that his urine had a high osmolality (concentration). What physiological mechanism could be responsible for this? What benefit does Charlie derive from this mechanism?
Drinking excessive amounts of water without excessive amounts of salt does not result in a prolonged increase in blood volume and pressure. The water does enter the blood from the intestine and momentarily raises the blood volume; at the same time, however, it dilutes the blood. Dilution of the blood decreases the plasma osmolality and thus inhibits the release of ADH. With less ADH there is less reabsorption of filtrate in the kidneys—a larger volume of urine is excreted. Water is therefore a diuretic—a substance that promotes urine formation—because it inhibits the release of antidiuretic hormone.
An increase in blood volume can thus be compensated by a fall in ADH secretion. However, expanded blood volume also
Cardiac Output, Blood Flow, and Blood Pressure stimulates stretch receptors in the left atrium of the heart, causing the increased secretion of a different hormone. This is a polypeptide known as atrial natriuretic peptide (discussed in a separate section shortly). This hormone promotes the increased excretion of salt and water in the urine, thereby helping to lower the blood volume.
During prolonged exercise, particularly on a warm day, a substantial amount of water (up to 900 ml per hour) may be lost from the body through sweating. The lowering of blood volume that results decreases the ability of the body to dissipate heat, and the consequent overheating of the body can cause ill effects and put an end to the exercise. The need for athletes to remain well hydrated is commonly recognized, but drinking pure water may not be the answer. This is because blood sodium is lost in sweat, so that a lesser amount of water is required to dilute the blood osmolality back to normal. When the blood osmolality is normal, the urge to drink is extinguished. For these reasons, athletes performing prolonged endurance exercise should drink solutions containing sodium (as well as carbohydrates for energy), and they should drink at a predetermined rate rather than at a rate determined only by thirst.
From the preceding discussion, it is clear that a certain amount of dietary salt is required to maintain blood volume and pressure. Since Na+ and Cl- are easily filtered in the kidneys, a mechanism must exist to promote the reabsorption and retention of salt when the dietary salt intake is too low. Aldosterone, a steroid hormone secreted by the adrenal cortex, stimulates the reabsorption of salt by the kidneys. Aldosterone is thus a "salt-retaining hormone." Retention of salt indirectly promotes retention of water (in part, by the action of ADH, as previously discussed). The action of aldosterone produces an increase in blood volume, but, unlike ADH, it does not produce a change in plasma osmolality. This is because aldosterone promotes the reabsorption of salt and water in proportionate amounts, whereas ADH promotes only the reabsorption of water. Thus, unlike ADH, aldosterone does not act to dilute the blood.
The secretion of aldosterone is stimulated during salt deprivation, when the blood volume and pressure are reduced. The adrenal cortex, however, is not directly stimulated to secrete al-dosterone by these conditions. Instead, a decrease in blood volume and pressure activates an intermediate mechanism, described in the next section.
Throughout most of human history, salt was in short supply and was therefore highly valued. Moorish merchants in the sixth century traded an ounce of salt for an ounce of gold, and salt cakes were used as money in Abyssinia. Part of a Roman soldier's pay was given in salt—a practice from which the word salary (sal = salt) derives. Salt was also used to purchase slaves—hence the phrase "worth his salt."
I Blood pressure I Blood flow to kidneys
Juxtaglomerular apparatus in kidneys
Angiotensin I ACE
Vasoconstriction of arterioles
Salt and water retention by kidneys
■ Figure 14.12 The renin-angiotensin-aldosterone system. This system helps to maintain homeostasis through the negative feedback control of blood volume and pressure. (ACE = angiotensin-converting enzyme.)
When the blood flow and pressure are reduced in the renal artery (as they would be in the low-blood-volume state of salt deprivation), a group of cells in the kidneys called the juxtaglomerular apparatus secretes the enzyme renin into the blood. This enzyme cleaves a ten-amino-acid polypeptide called angiotensin I from a plasma protein called angiotensinogen. As angiotensin I passes through the capillaries of the lungs, an angiotensin-converting enzyme (ACE) removes two amino acids. This leaves an eight-amino-acid polypeptide called angiotensin II (fig. 14.12). Conditions of salt deprivation, low blood volume, and low blood pressure, in summary, cause increased production of angiotensin II in the blood.
Angiotensin II exerts numerous effects that produce a rise in blood pressure. This rise in pressure is partly due to vasoconstriction and partly to increases in blood volume. Vasoconstriction of arterioles and small muscular arteries is produced directly by the effects of angiotensin II on the smooth muscle layers of these vessels. The increased blood volume is an indirect effect of angiotensin II.
Angiotensin II promotes a rise in blood volume by means of two mechanisms: (1) thirst centers in the hypothalamus are stimulated by angiotensin II, and thus more water is ingested, and (2) secretion of aldosterone from the adrenal cortex is stimulated by angiotensin II, and higher aldosterone secretion causes more salt and water to be retained by the kidneys. The relationship between angiotensin II and aldosterone is sometimes described as the renin-angiotensin-aldosterone system.
Clinical Investigation Clues
Remember that Charlie's urine had virtually no Na+ in it.
■ What physiological mechanism is responsible for this?
■ What benefits does Charlie derive from this mechanism?
The renin-angiotensin-aldosterone system can also work in the opposite direction: high salt intake, leading to high blood volume and pressure, normally inhibits renin secretion. With less angiotensin II formation and less aldosterone secretion, less salt is retained by the kidneys and more is excreted in the urine. Unfortunately, many people with chronically high blood pressure may have normal or even elevated levels of renin secretion. In these cases, the intake of salt must be lowered to match the impaired ability to excrete salt in the urine.
C>ne °f the newer classes of drugs that can be used to treat hypertension (high blood pressure) are the __jTri angiotensin-converting enzyme, or ACE, inhibitors. These drugs (such as captopril) block the formation of angiotensin II, thus reducing its vasoconstrictor effect. The ACE inhibitors also increase the activity of bradykinin, a polypeptide that promotes vasodilation. The reduced formation of angiotensin II and increased action of bradykinin result in vasodilation, which decreases the total peripheral resistance. Because this reduces the afterload of the heart, the ACE inhibitors are also used to treat left ventricular hypertrophy and congestive heart failure. Another new class of antihypertensive drugs allows angiotensin II to be formed but selectively blocks the angiotensin II receptors.
As described in the previous section, a fall in blood volume is compensated for by renal retention of fluid through activation of the renin-angiotensin-aldosterone system. An increase in blood volume, conversely, is compensated for by renal excretion of a larger volume of urine. Experiments suggest that the increase in water excretion under conditions of high blood volume is at least partly due to an increase in the excretion of Na+ in the urine, or natriuresis (natrium = sodium; uresis = making water).
Increased Na+ excretion (natriuresis) may be produced by a decline in aldosterone secretion, but there is evidence that there is a separate hormone that stimulates natriuresis. This natriuretic hormone would thus be antagonistic to aldosterone and would promote Na+ and water excretion in the urine in response to a rise in blood volume. A polypeptide hormone with these properties, identified as atrial natriuretic peptide (ANP), is produced by the atria of the heart. By promoting salt and water excretion in the urine, ANP can act to lower the blood volume and pressure. This is analogous to the action of diuretic drugs taken by people with hypertension, as described later in this chapter.
In addition to its stimulation of salt and water excretion by the kidneys. ANP also antagonizes various actions of angiotensin II. As a result of this action, ANP decreases the secretion of aldosterone and promotes vasodilation.
1. Describe the composition of tissue (interstitial) fluid. Using a flow diagram, explain how tissue fluid is formed and how it is returned to the vascular system.
2. Define the term edema and describe four different mechanisms that can produce this condition.
3. Describe the effects of dehydration on blood and urine volumes. What cause-and-effect mechanism is involved?
4. Explain why salt deprivation causes increased salt and water retention by the kidneys.
5. Describe the actions of atrial natriuretic peptide and explain their significance.
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Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...