Renal

Question 1

Relative amounts of extracellular fluid distributed between the plasma and interstitial spaces.

Answer 1

Determined mainly by the balance of hydrostatic and colloid osmotic forces across the capillary membranes

Question 2

Distribution of fluid between intracellular and extracellular compartments

Answer 2

Determined mainly by the osmotic effect of the smaller solutes— especially sodium, chloride, and other electrolytes— acting across the cell membrane. The reason for this is that the cell membranes are highly permeable to water but relatively impermeable to even small ions such as sodium and chloride. Therefore, water moves across the cell membrane rapidly and the intracellular fluid remains isotonic with the extracellular fluid.

Question 3

If the cell membrane is exposed to pure water?

Answer 3

The osmolarity of intracellular fluid is 282 mOsm/L, the potential osmotic pressure that can develop across the cell membrane is more than 5400 mm Hg. This demonstrates the large force
that can move water across the cell membrane when the intracellular and extracellular fluids are not in osmotic equilibrium.

Question 4

CAUSES OF HYPONATREMIA

Answer 4

EXCESS WATER OR LOSS OF SODIUM Decreased plasma sodium concentration can result from loss of sodium chloride from the extracellular fluid or addition of excess water to the extracellular fluid (Table 25-4). A primary loss of sodium chloride usually results in hyponatremia and dehydration and is associated with decreased extracellular fluid volume. Conditions that can cause hyponatremia as a result of loss of sodium chloride include diarrhea and vomiting. Overuse of diuretics that inhibit the ability of the kidneys to conserve sodium and certain types of sodium­wasting kidney diseases can also cause modest degrees of hyponatremia. Finally, Addison’s disease, which results from decreased secretion of the hormone aldosterone, impairs the ability of the kidneys to reabsorb sodium and can cause a modest degree of hyponatremia. Hyponatremia can also be associated with excess water retention, which dilutes the sodium in the extracellular fluid, a condition that is referred to as hyponatremia— overhydration. For example, excessive secretion of antidiuretic hormone, which causes the kidney tubules to reabsorb more water, can lead to hyponatremia and overhydration.

Question 5

CONSEQUENCES OF HYPONATREMIA

Answer 5

CELL SWELLING Rapid changes in cell volume as a result of hyponatremia can have profound effects on tissue and organ function, especially the brain. A rapid reduction in plasma sodium concentration, for example, can cause brain cell edema and neurological symptoms, including headache, nausea, lethargy, and disorientation. If plasma sodium concentration rapidly falls below 115 to 120 mmol/L, brain swelling may lead to seizures, coma, permanent brain damage, and death. Because the skull is rigid, the brain cannot increase its volume by more than about 10 percent without it being forced down the neck (herniation), which can lead to permanent brain injury and death. When hyponatremia evolves more slowly over several days, the brain and other tissues respond by transporting sodium, chloride, potassium, and organic solutes, such as glutamate, from the cells into the extracellular compartment. This response attenuates osmotic flow of water into the cells and swelling of the tissues (Figure 25-7). Transport of solutes from the cells during slowly
developing hyponatremia, however, can make the brain vulnerable to injury if the hyponatremia is corrected too rapidly. When hypertonic solutions are added too rapidly to correct hyponatremia, this intervention can outpace the brain’s ability to recapture the solutes lost from the cells and may lead to osmotic injury of the neurons that is associated with demyelination, a loss of the myelin sheath from nerves. This osmotic­mediated demyelination of neurons can be avoided by limiting the correction of chronic hyponatremia to less than 10 to 12 mmol/L in 24 hours and to less than 18 mmol/L in 48 hours. This slow rate of correction permits the brain to recover the lost osmoles that have occurred as a result of adaptation to chronic hyponatremia. Hyponatremia is the most common electrolyte disorder encountered in clinical practice and may occur in up to 15% to 25% of hospitalized patients.

Question 6

CAUSES OF HYPERNATREMIA

Answer 6

Increased plasma sodium concentration, which also causes increased osmolarity, can be due to either loss of water from the extracellular fluid, which concentrates the sodium ions, or excess sodium in the extracellular fluid.Primary loss of water from the extracellular fluid results in hypernatremia and dehydration. This condition can occur from an inability to secrete antidiuretic hormone, which is needed for the kidneys to conserve water. As a result of lack of antidiuretic hormone, the kidneys excrete large amounts of dilute urine (a disorder referred to
as “central” diabetes insipidus), causing dehydration and increased concentration of sodium chloride in the extracellular fluid. In certain types of renal diseases, the kidneys cannot respond to antidiuretic hormone, causing a type of “nephrogenic” diabetes insipidus. A more common cause of hypernatremia associated with decreased extracellular fluid volume is simple dehydration caused by water intake that is less than water loss, as can occur with sweating during prolonged, heavy exercise. Hypernatremia can also occur when excessive sodium chloride is added to the extracellular fluid. This often results in hypernatremia—overhydration because excess extracellular sodium chloride is usually associated with at least some degree of water retention by the kidneys as well. For example, excessive secretion of the sodiumretaining hormone aldosterone can cause a mild degree of hypernatremia and overhydration. The reason that the hypernatremia is not more severe is that the sodium retention caused by increased aldosterone secretion also stimulates secretion of antidiuretic hormone and causes the kidneys to also reabsorb greater amounts of water. Thus, in analyzing abnormalities of plasma sodium concentration and deciding on proper therapy, one should first determine whether the abnormality is caused by a primary loss or gain of sodium or a primary loss or gain of water.

Question 7

CONSEQUENCES OF HYPERNATREMIA

Answer 7

CELL SHRINKAGE Hypernatremia is much less common than hyponatremia, and severe symptoms usually occur only with rapid and large increases in the plasma sodium concentration above 158 to 160 mmol/L. One reason for this phenomenon is that hypernatremia promotes intense thirst and stimulates secretion of antidiuretic hormone, which both protect against a large increase in plasma and extracellular fluid sodium, as discussed in Chapter 29. However, severe hypernatremia can occur in patients with hypothalamic lesions that impair their sense of thirst, in infants who may not have ready access to water, in elderly patients with altered mental status, or in persons with diabetes insipidus. Correction of hypernatremia can be achieved by administering hypo­osmotic sodium chloride or dextrose solutions. However, it is prudent to correct the hypernatremia slowly in patients who have had chronic increases in plasma sodium concentration because hypernatremia also activates defense mechanisms that protect the cell from changes in volume. These defense mechanisms are opposite to those that occur for hyponatremia and consist of mechanisms that increase the intracellular concentration of sodium and other solutes.

Question 8

INTRACELLULAR EDEMA

Answer 8

Three conditions are especially prone to cause intracellular swelling: (1) hyponatremia, as discussed earlier;
(2) depression of the metabolic systems of the tissues; and (3) lack of adequate nutrition to the cells. For example, when blood flow to a tissue is decreased, the delivery
of oxygen and nutrients is reduced. If the blood flow becomes too low to maintain normal tissue metabolism, the cell membrane ionic pumps become depressed. When the pumps become depressed, sodium ions that normally leak into the interior of the cell can no longer be pumped out of the cells and the excess intracellular sodium ions cause osmosis of water into the cells. Sometimes this process can increase intracellular volume of a tissue area—even of an entire ischemic leg, for example—to
two to three times normal. When such an increase in intracellular volume occurs, it is usually a prelude to death of the tissue. Intracellular edema can also occur in inflamed tissues. Inflammation usually increases cell membrane permeability, allowing sodium and other ions to diffuse into the interior of the cell, with subsequent osmosis of water into the cells.

Question 9

EXTRACELLULAR EDEMA

Answer 9

Extracellular fluid edema occurs when excess fluid accumulates in the extracellular spaces. There are two general causes of extracellular edema: (1) abnormal leakage of fluid from the plasma to the interstitial spaces across
the capillaries, and (2) failure of the lymphatics to return fluid from the interstitium back into the blood, often called lymphedema. The most common clinical cause of interstitial fluid accumulation is excessive capillary fluid filtration.

Question 10

Factors That Can Increase Capillary Filtration

Answer 10

• capillary filtration coefficient (the product of the permeability and surface area of the capillaries)=Kf
• Net filtration pressure (capillary hydrostatic pressure, interstitial fluid hydrostatic pressure, capillary plasma colloid osmotic pressure, interstitial fluid colloid osmotic pressure)

F=Kf*NFP

Question 11

Lymphedema

Answer 11

Failure of the Lymph Vessels to Return Fluid and Protein to the Blood When lymphatic function is greatly impaired as a result of blockage or loss of the lymph vessels, edema can become especially severe because plasma proteins that leak into the interstitium have no other way to be removed. The rise in protein concentration raises the colloid osmotic pressure of the interstitial fluid, which draws even more fluid out of the capillaries. Blockage of lymph flow can be especially severe with infections of the lymph nodes, such as occurs with infection by filaria nematodes (Wuchereria bancrofti), which are microscopic, threadlike worms. The adult worms live in the human lymph system and are spread from person to person by mosquitoes. People with filarial infections can have severe lymphedema and elephantiasis and men can have swelling of the scrotum, called hydrocele. Lymphatic filariasis affects more than 120 million people in 80 countries throughout the tropics and subtropics
of Asia, Africa, the Western Pacific, and parts of the Caribbean and South America. Lymphedema can also occur in persons who have certain types of cancer or after surgery in which lymph vessels are removed or obstructed. For example, large numbers of lymph vessels are removed during radical mastectomy, impairing removal of fluid from the breast and arm areas and causing edema and swelling of the tissue spaces. A few lymph vessels eventually regrow after this type of surgery, and thus the interstitial edema is usually temporary.

Question 12

CAUSES OF EXTRACELLULAR EDEMA

Answer 12

I. Increased capillary pressure

A. Excessive kidney retention of salt and water

1. Acute or chronic kidney failure
2. Mineralocorticoid excess

B. High venous pressure and venous constriction

1. Heart failure
2. Venous obstruction
3. Failure of venous pumps
   (a) Paralysis of muscles
   (b) Immobilization of parts of the body
   (c) Failure of venous valves

C. Decreased arteriolar resistance

1. Excessive body heat
2. Insufficiency of sympathetic nervous system
3. Vasodilator drugs

II. Decreased plasma proteins

A. Loss of proteins in urine (nephrotic syndrome)

B. Loss of protein from denuded skin areas

1. Burns
2. Wounds

C. Failure to produce proteins

1. Liver disease (e.g., cirrhosis)
2. Serious protein or caloric malnutrition

III. Increased capillary permeability

A. Immune reactions that cause release of histamine and other immune products

B. Toxins

C. Bacterial infections

D. Vitamin deficiency, especially vitamin C

E. Prolonged ischemia

F. Burns

IV. Blockage of lymph return

A. Cancer

B. Infections (e.g., filaria nematodes)

C. Surgery

D. Congenital absence or abnormality of lymphatic vessels

Question 13

Edema Caused by Heart Failure

Answer 13

One of the most serious and common causes of edema is heart failure. In heart failure, the heart fails to pump blood normally from the veins into the arteries, which raises venous pressure and capillary pressure, causing increased capillary filtration. In addition, the arterial pressure tends to fall, causing decreased excretion of salt and water by the kidneys, which causes still more edema. Also, blood flow to the kidneys is reduced in persons with heart failure, and this reduced blood flow stimulates secretion of renin, causing increased formation of angiotensin II and increased secretion of aldosterone, both of which cause additional salt and water retention by the kidneys. Thus, in persons with untreated heart failure, all these factors acting together cause serious generalized extracellular edema. In patients with left­sided heart failure but without significant failure of the right side of the heart, blood is pumped into the lungs normally by the right side of the heart but cannot escape easily from the pulmonary veins to the left side of the heart because this part of the heart has been greatly weakened. Consequently, all the pulmonary vascular pressures, including pulmonary capillary pressure, rise far above normal, causing serious and lifethreatening pulmonary edema. When untreated, fluid accumulation in the lungs can rapidly progress, causing death within a few hours.

Question 14

Edema Caused by Decreased Kidney Excretion of Salt and Water

Answer 14

Most sodium chloride added to the blood remains in the extracellular compartment, and only small amounts enter the cells. Therefore, in kidney diseases that compromise urinary excretion of salt and water, large amounts of sodium chloride and water are added to the extracellular fluid. Most of this salt and water leaks from the blood into the interstitial spaces, but some remains
in the blood. The main effects of this are (1) widespread increases in interstitial fluid volume (extracellular edema) and (2) hypertension because of the increase in blood volume, as explained in Chapter 19. As an example, in children who have acute glomerulonephritis, in which the renal glomeruli are injured by inflammation and therefore fail to filter adequate amounts of fluid, serious extracellular fluid edema also develops; along with the edema, severe hypertension usually develops.

Question 15

Edema Caused by Decreased Plasma Proteins

Answer 15

Failure to produce normal amounts of proteins or leakage of proteins from the plasma causes the plasma colloid osmotic pressure to fall. This leads to increased capillary filtration throughout the body and extracellular edema. One of the most important causes of decreased plasma protein concentration is loss of proteins in the urine
in certain kidney diseases, a condition referred to as nephrotic syndrome. Multiple types of renal diseases can damage the membranes of the renal glomeruli, causing the membranes to become leaky to the plasma proteins and often allowing large quantities of these proteins to pass into the urine. When this loss exceeds the ability of the body to synthesize proteins, a reduction in plasma protein concentration occurs. Serious generalized edema occurs when the plasma protein concentration falls below 2.5 g/100 ml. Cirrhosis of the liver is another condition that causes a reduction in plasma protein concentration. Cirrhosis means development of large amounts of fibrous tissue among the liver parenchymal cells. One result is failure of these cells to produce sufficient plasma proteins, leading to decreased plasma colloid osmotic pressure and the generalized edema that goes with this condition. Another way liver cirrhosis causes edema is that the liver fibrosis sometimes compresses the abdominal portal venous drainage vessels as they pass through the liver before emptying back into the general circulation. Blockage of this portal venous outflow raises capillary hydrostatic pressure throughout the gastrointestinal area and further increases filtration of fluid out of the plasma into the intra­abdominal areas. When this occurs, the combined effects of decreased plasma protein concentration and high portal capillary pressures cause transudation of large amounts of fluid and protein into the abdominal cavity, a condition referred to as ascites.

Question 16

Vasa recta

Answer 16

For the juxtamedullary nephrons, long efferent arterioles extend from the glomeruli down into the outer medulla and then divide into specialized peritubular capillaries called vasa recta that extend downward into the medulla, lying side by side with the loops of Henle. Like the loops of Henle, the vasa recta return toward the cortex and empty into the cortical veins. This specialized network of capillaries in the medulla plays an essential role in the formation of a concentrated urine.

Question 17

COMPOSITION OF THE GLOMERULAR FILTRATE

Answer 17

Like most capillaries, the glomerular capillaries are
relatively impermeable to proteins, so the filtered fluid (called the glomerular filtrate) is essentially protein free and devoid of cellular elements, including red blood cells. The concentrations of other constituents of the glomerular filtrate, including most salts and organic molecules, are similar to the concentrations in the plasma. Exceptions to this generalization include a few low molecular weight substances such as calcium and fatty acids that are not freely filtered because they are partially bound to the plasma proteins. For example, almost one half of the plasma calcium and most of the plasma fatty acids are bound to proteins, and these bound portions are not filtered through the glomerular capillaries.

Question 18

Filtration fraction

Answer 18

Filtration fraction= GFR/Renal plasma flow

The fraction of the renal plasma flow that is filtered (the filtration fraction) averages about 0.2, which means that about 20 percent of the plasma flowing through the kidney is filtered through the glomerular capillaries

Question 19

GLOMERULAR CAPILLARY MEMBRANE

Answer 19

The glomerular capillary membrane is similar to that of other capillaries, except that it has three (instead of the usual two) major layers: (1) the endothelium of the capillary, (2) a basement membrane, and (3) a layer of epithelial cells (podocytes) surrounding the outer surface of the capillary basement membrane. Together, these layers make up the filtration barrier, which, despite the three layers, filters several hundred times as much water and solutes as the usual capillary membrane. Even with this high rate of filtration, the glomerular capillary membrane normally prevents filtration of plasma proteins. The high filtration rate across the glomerular capillary membrane is due partly to its special characteristics.
The capillary endothelium is perforated by thousands of small holes called fenestrae, similar to the fenestrated capillaries found in the liver, although smaller than the fenestrae of the liver. Although the fenestrations are relatively large, endothelial cell proteins are richly endowed with fixed negative charges that hinder the passage of plasma proteins. Surrounding the endothelium is the basement membrane, which consists of a meshwork of collagen and proteoglycan fibrillae that have large spaces through which large amounts of water and small solutes can filter. The basement membrane effectively prevents filtration of plasma proteins, in part because of strong negative electrical charges associated with the proteoglycans. The final part of the glomerular membrane is a layer of epithelial cells that line the outer surface of the glomerulus. These cells are not continuous but have long footlike processes (podocytes) that encircle the outer surface of the capillaries (see Figure 27-2). The foot processes are separated by gaps called slit pores through which the glomerular filtrate moves. The epithelial cells, which also have negative charges, provide additional restriction to filtration of plasma proteins. Thus, all layers of the glomerular capillary wall provide a barrier to filtration of plasma proteins.

Question 20

What filterability in the glomerulus depend on?

Answer 20

Filterability of Solutes Is Inversely Related to Their Size. The glomerular capillary membrane is thicker than most other capillaries, but it is also much more porous and therefore filters fluid at a high rate. Despite the high filtration rate, the glomerular filtration barrier is selective in determining which molecules will filter, based on their size and electrical charge. Table 27-1 lists the effect of molecular size on filterability of different molecules. A filterability of 1.0 means that the substance is filtered as freely as water, whereas a filterability of 0.75 means that the substance is filtered only 75 percent as rapidly as water. Note that electrolytes such as sodium and small organic compounds such as glucose are freely filtered. As the molecular weight of the molecule approaches that of albumin, the filterability rapidly decreases, approaching zero.

Negatively Charged Large Molecules Are Filtered Less Easily Than Positively Charged Molecules of Equal Molecular Size. The molecular diameter of the plasma protein albumin is only about 6 nanometers, whereas the pores of the glomerular membrane are thought to be about 8 nanometers (80 angstroms). Albumin is restricted from filtration, however, because
of its negative charge and the electrostatic repulsion exerted by negative charges of the glomerular capillary wall proteoglycans. Figure 27-3 shows how electrical charge affects the filtration of different molecular weight dextrans by
the glomerulus. Dextrans are polysaccharides that can
be manufactured as neutral molecules or with negative
or positive charges. Note that for any given molecular radius, positively charged molecules are filtered much more readily than are negatively charged molecules. Neutral dextrans are also filtered more readily than are negatively charged dextrans of equal molecular weight. The reason for these differences in filterability is that
the negative charges of the basement membrane and the podocytes provide an important means for restricting large negatively charged molecules, including the plasma proteins. In certain kidney diseases, the negative charges on the basement membrane are lost even before there are noticeable changes in kidney histology, a condition referred to as minimal change nephropathy. The cause for this loss of negative charges is still unclear but is believed to be related to an immunological response with abnormal T­cell secretion of cytokines that reduce anions in the glomerular capillary or podocyte proteins. As a result of this loss of negative charges on the basement membranes, some of the lower molecular weight proteins, especially albumin, are filtered and appear in the urine, a condition known as proteinuria or albuminuria. Minimal change nephropathy is most common in young children but can also occur in adults, especially in those who have autoimmune disorders.

Question 21

FILTRATION COEFFICIENT

Answer 21

The Kf is a measure of the product of the hydraulic conductivity and surface area of the glomerular capillaries. The Kf cannot be measured directly, but it is estimated experimentally by dividing the rate of glomerular filtration by net filtration pressure. Because the total GFR for both kidneys is about 125 ml/min and the net filtration pressure is 10 mm Hg, the normal Kf is calculated to be about 12.5 ml/min/ mm Hg of filtration pressure. When Kf is expressed per 100 grams of kidney weight, it averages about 4.2 ml/min/ mm Hg, a value about 400 times as high as the Kf of most other capillary systems of the body; the average Kf of many other tissues in the body is only about 0.01 ml/ min/mm Hg per 100 grams. This high Kf for the glomerular capillaries contributes to their rapid rate of fluid filtration. Although increased Kf raises GFR and decreased Kf reduces GFR, changes in Kf probably do not provide a primary mechanism for the normal day­to­day regulation of GFR. Some diseases, however, lower Kf by reducing the number of functional glomerular capillaries (thereby reducing the surface area for filtration) or by increasing the thickness of the glomerular capillary membrane and reducing its hydraulic conductivity. For example, chronic, uncontrolled hypertension and diabetes mellitus gradually reduce Kf by increasing the thickness of the glomerular capillary basement membrane and, eventually, by damaging the capillaries so severely that there is loss of capillary function.

Question 22

INCREASED BOWMAN’S CAPSULE HYDROSTATIC PRESSURE

Answer 22

Direct measurements, using micropipettes, of hydrostatic pressure in Bowman’s capsule and at different points
in the proximal tubule in experimental animals suggest that a reasonable estimate for Bowman’s capsule pressure in humans is about 18 mm Hg under normal conditions. Increasing the hydrostatic pressure in Bowman’s capsule reduces GFR, whereas decreasing this pressure raises GFR. However, changes in Bowman’s capsule pressure normally do not serve as a primary means for regulating GFR. In certain pathological states associated with obstruction of the urinary tract, Bowman’s capsule pressure can increase markedly, causing serious reduction of GFR. For example, precipitation of calcium or of uric acid may lead to “stones” that lodge in the urinary tract, often in the ureter, thereby obstructing outflow of the urinary tract and raising Bowman’s capsule pressure. This situation reduces GFR and eventually can cause hydronephrosis (distention and dilation of the renal pelvis and calyces) and can damage or even destroy the kidney unless the obstruction is relieved.

Question 23

INCREASED GLOMERULAR CAPILLARY COLLOID OSMOTIC PRESSURE

Answer 23

As blood passes from the afferent arteriole through
the glomerular capillaries to the efferent arterioles, the plasma protein concentration increases about 20 percent (Figure 27-5). The reason for this increase is that about one fifth of the fluid in the capillaries filters into Bowman’s capsule, thereby concentrating the glomerular plasma proteins that are not filtered. Assuming that the normal colloid osmotic pressure of plasma entering the glomerular capillaries is 28 mm Hg, this value usually rises to about 36 mm Hg by the time the blood reaches the efferent end of the capillaries. Therefore, the average colloid osmotic pressure of the glomerular capillary plasma proteins is midway between 28 and 36 mm Hg, or about 32 mm Hg. Thus, two factors that influence the glomerular capillary colloid osmotic pressure are (1) the arterial plasma colloid osmotic pressure and (2) the fraction of plasma filtered by the glomerular capillaries (filtration fraction). Increasing the arterial plasma colloid osmotic pressure raises the glomerular capillary colloid osmotic pressure, which in turn decreases the GFR. Increasing the filtration fraction also concentrates the plasma proteins and raises the glomerular colloid osmotic pressure (see Figure 27-5). Because the filtration fraction is defined as GFR/renal plasma flow, the filtration fraction can be increased either by raising the GFR or by reducing renal plasma flow. For example, a reduction in renal plasma flow with no initial change in GFR would tend to increase the filtration fraction, which would raise the glomerular capillary colloid osmotic pressure and tend to reduce the GFR. For this reason, changes in renal blood flow can influence GFR independently of changes in glomerular hydrostatic pressure. With increasing renal blood flow, a lower fraction of the plasma is initially filtered out of the glomerular capillaries, causing a slower rise in the glomerular capillary colloid osmotic pressure and less inhibitory effect on the GFR. Consequently, even with a constant glomerular hydrostatic pressure, a greater rate of blood flow into the glomerulus tends to increase the GFR and a lower rate of blood flow into the glomerulus tends to decrease the GFR

Question 24

INCREASED GLOMERULAR CAPILLARY HYDROSTATIC PRESSURE

Answer 24

The glomerular capillary hydrostatic pressure has been estimated to be about 60 mm Hg under normal conditions. Changes in glomerular hydrostatic pressure serve as the primary means for physiological regulation of GFR. Increases in glomerular hydrostatic pressure raise the GFR, whereas decreases in glomerular hydrostatic pressure reduce the GFR. Glomerular hydrostatic pressure is determined by three variables, each of which is under physiological control: (1) arterial pressure, (2) afferent arteriolar resistance, and (3) efferent arteriolar resistance. Increased arterial pressure tends to raise glomerular hydrostatic pressure and, therefore, to increase the GFR. (However, as discussed later, this effect is buff ered by autoregulatory mechanisms that maintain a relatively constant glomerular pressure as blood pressure fluctuates.) Increased resistance of afferent arterioles reduces glomerular hydrostatic pressure and decreases the GFR (Figure 27-6). Conversely, dilation of the afferent arterioles increases both glomerular hydrostatic pressure
and GFR. Constriction of the efferent arterioles increases the resistance to outflow from the glomerular capillaries. This mechanism raises glomerular hydrostatic pressure, and as long as the increase in efferent resistance does not reduce renal blood flow too much, GFR increases slightly (see Figure 27-6). However, because efferent arteriolar constriction also reduces renal blood flow, filtration fraction
and glomerular colloid osmotic pressure increase as efferent arteriolar resistance increases. Therefore, if constriction of efferent arterioles is severe (more than about a threefold increase in efferent arteriolar resistance), the rise in colloid osmotic pressure exceeds the increase in glomerular capillary hydrostatic pressure caused by efferent arteriolar constriction. When this situation occurs, the net force for filtration actually decreases, causing a reduction in GFR. Thus, efferent arteriolar constriction has a biphasic effect on GFR (Figure 27-7). At moderate levels of constriction, there is a slight increase in GFR, but with severe constriction, there is a decrease in GFR. The primary cause of the eventual decrease in GFR is as follows: As efferent constriction becomes severe and as plasma protein concentration increases, there is a rapid, nonlinear increase in colloid osmotic pressure caused by the Donnan effect; the higher the protein concentration, the more rapidly the colloid osmotic pressure rises because of the interaction of ions bound to the plasma proteins, which also exert an osmotic effect, as discussed in Chapter 16. To summarize, constriction of afferent arterioles reduces GFR. However, the effect of efferent arteriolar constriction depends on the severity of the constriction; modest efferent constriction raises GFR, but severe efferent constriction (more than a threefold increase in resistance) tends to reduce GFR.

Question 25

RENAL BLOOD FLOW AND OXYGEN CONSUMPTION

Answer 25

On a per­gram­weight basis, the kidneys normally consume oxygen at twice the rate of the brain but have almost seven times the blood flow of the brain. Thus, the oxygen delivered to the kidneys far exceeds their metabolic needs, and the arterial­venous extraction of oxygen is relatively low compared with that of most other tissues. A large fraction of the oxygen consumed by the kidneys is related to the high rate of active sodium reabsorption by the renal tubules. If renal blood flow and GFR are reduced and less sodium is filtered, less sodium is reabsorbed and less oxygen is consumed. Therefore, renal oxygen consumption varies in proportion to renal tubular sodium reabsorption, which in turn is closely related to GFR and the rate of sodium filtered (Figure 27-8). If glomerular filtration completely ceases, renal sodium reabsorption also ceases and oxygen consumption decreases to about one­fourth normal. This residual oxygen consumption reflects the basic metabolic needs of the renal cells.

Question 26

DETERMINANTS OF RENAL BLOOD FLOW

Answer 26

Renal blood flow is determined by the pressure gradient across the renal vasculature (the difference between renal artery and renal vein hydrostatic pressures), divided by the total renal vascular resistance. Renal artery pressure is about equal to systemic arterial pressure, and renal vein pressure averages about 3
to 4 mm Hg under most conditions. As in other vascular beds, the total vascular resistance through the kidneys is determined by the sum of the resistances in the individual vasculature segments, including the arteries, arterioles, capillaries, and veins (Table 27-3). Most of the renal vascular resistance resides in three major segments: interlobular arteries, afferent arterioles, and efferent arterioles. Resistance of these vessels is controlled by the sympathetic nervous system, various hormones, and local internal renal control mechanisms, as discussed later. An increase in the resistance of any of the vascular segments of the kidneys tends to reduce the renal blood flow, whereas a decrease in vascular resistance increases renal blood flow if renal artery and renal vein pressures remain constant. Although changes in arterial pressure have some influence on renal blood flow, the kidneys have effective mechanisms for maintaining renal blood flow and GFR relatively constant over an arterial pressure range between 80 and 170 mm Hg, a process called autoregulation. This capacity for autoregulation occurs through mechanisms that are completely intrinsic to the kidneys, as discussed later in this chapter.

Question 27

STRONG SYMPATHETIC NERVOUS SYSTEM ACTIVATION EFFECT ON KIDNEY

Answer 27

Essentially all the blood vessels of the kidneys, including the afferent and the efferent arterioles, are richly innervated by sympathetic nerve fibers. Strong activation of
the renal sympathetic nerves can constrict the renal arterioles and decrease renal blood flow and GFR. Moderate or mild sympathetic stimulation has little influence on renal blood flow and GFR. For example, reflex activation of the sympathetic nervous system resulting from moderate decreases in pressure at the carotid sinus baroreceptors or cardiopulmonary receptors has little influence on renal blood flow or GFR. However, as discussed in Chapter 28, even mild increases in renal sympathetic activity can cause decreased sodium and water excretion by increasing renal tubular reabsorption. The renal sympathetic nerves seem to be most important in reducing GFR during severe, acute disturbances lasting for a few minutes to a few hours, such as
those elicited by the defense reaction, brain ischemia, or severe hemorrhage. In the healthy resting person, sympathetic tone appears to have little influence on renal blood flow.

Question 28

Angiotensin II effect on kidney

Answer 28

A powerful renal vasoconstrictor, angiotensin II, can be considered a circulating hormone and a locally produced autacoid because it is formed in the kidneys and in the systemic circulation. Receptors for angiotensin II are present in virtually all blood vessels of the kidneys. However, the preglomerular blood vessels, especially the afferent arterioles, appear to be relatively protected from angiotensin II–mediated constriction in most physiological conditions associated with activation of the reninangiotensin system, such as during a low­sodium diet or reduced renal perfusion pressure due to renal artery stenosis. This protection is due to release of vasodilators, especially nitric oxide and prostaglandins, which counteract the vasoconstrictor effects of angiotensin II in these blood vessels. The efferent arterioles, however, are highly sensitive to angiotensin II. Because angiotensin II preferentially constricts efferent arterioles in most physiological conditions, increased angiotensin II levels raise glomerular hydrostatic pressure while reducing renal blood flow. It should be kept in mind that increased angiotensin II formation usually occurs in circumstances associated with decreased arterial pressure or volume depletion, which tend to decrease GFR. In these circumstances, the increased level of angiotensin II, by constricting efferent arterioles, helps prevent decreases in glomerular hydrostatic pressure and GFR; at the same time, though, the reduction in renal blood flow caused by efferent arteriolar constriction contributes to decreased flow through the peritubular capillaries, which in turn increases reabsorption of sodium and water, as discussed in Chapter 28. Thus, increased angiotensin II levels that occur with a low­sodium diet or volume depletion help maintain GFR and normal excretion of metabolic waste products such as urea and creatinine that depend on glomerular filtration for their excretion; at the same time, the angiotensin II–induced constriction of efferent arterioles increases tubular reabsorption of sodium and water, which helps restore blood volume and blood pressure.

Question 29

Endothelial-Derived Nitric Oxide

Answer 29

An autacoid that decreases renal vascular resistance and is released
by the vascular endothelium throughout the body is endothelial-derived nitric oxide. A basal level of nitric oxide production appears to be important for maintaining vasodilation of the kidneys because it allows the kidneys to excrete normal amounts of sodium and water. Therefore, administration of drugs that inhibit formation of nitric oxide increases renal vascular resistance and decreases GFR and urinary sodium excretion, eventually causing high blood pressure. In some hypertensive patients or in patients with atherosclerosis, damage of the vascular endothelium and impaired nitric oxide production may contribute to increased renal vasoconstriction and elevated blood pressure.

Question 30

Prostaglandins and Bradykinin

Answer 30

Hormones and autacoids that cause vasodilation and increased renal blood flow and GFR include the prostaglandins (PGE2 and PGI2) and bradykinin. These substances are discussed in Chapter 17. Although these vasodilators do not appear to be of major importance in regulating renal blood flow or GFR in normal conditions, they may dampen the renal vasoconstrictor effects of the sympathetic nerves or angiotensin II, especially their effects to constrict the afferent arterioles. By opposing vasoconstriction of afferent arterioles, the prostaglandins may help prevent excessive reductions in GFR and renal blood flow. Under stressful conditions, such as volume depletion or after surgery, the administration of nonsteroidal anti­inflammatory agents, such as aspirin, that inhibit prostaglandin synthesis may cause significant reductions in GFR.

Question 31

IMPORTANCE OF GFR AUTOREGULATION IN PREVENTING EXTREME CHANGES IN RENAL EXCRETION

Answer 31

Although the renal autoregulatory mechanisms are not perfect, they do prevent potentially large changes in GFR and renal excretion of water and solutes that would otherwise occur with changes in blood pressure. One can understand the quantitative importance of autoregulation by considering the relative magnitudes of glomerular filtration, tubular reabsorption, and renal excretion and the changes in renal excretion that would occur without autoregulatory mechanisms. Normally, GFR is about 180 L/day and tubular reabsorption is 178.5 L/day, leaving 1.5 L/day of fluid to be excreted in the urine. In the absence of autoregulation, a relatively small increase in blood pressure (from 100 to 125 mm Hg) would cause a similar 25 percent increase in GFR (from about 180 to 225 L/day). If tubular reabsorption remained constant at 178.5 L/day, the urine flow would increase to 46.5 L/day (the difference between GFR and tubular reabsorption)—a total increase in urine of more than 30­fold. Because the total plasma volume is only about 3 liters, such a change would quickly deplete the blood volume. In reality, changes in arterial pressure usually exert much less of an effect on urine volume for two reasons: (1) renal autoregulation prevents large changes in GFR that would otherwise occur, and (2) there are additional adaptive mechanisms in the renal tubules that cause
them to increase their reabsorption rate when GFR rises, a phenomenon referred to as glomerulotubular balance (discussed in Chapter 28). Even with these special control mechanisms, changes in arterial pressure still have significant effects on renal excretion of water and sodium; this is referred to as pressure diuresis or pressure natriuresis, and it is crucial in the regulation of body fluid volumes and arterial pressure

Question 32

TUBULOGLOMERULAR FEEDBACK AND AUTOREGULATION OF GFR

Answer 32

Decreased Macula Densa Sodium Chloride Causes Dilation of Afferent Arterioles and Increased Renin Release. The macula densa cells sense changes in volume delivery to the distal tubule by way of signals that are
not completely understood. Experimental studies suggest that a decreased GFR slows the flow rate in the loop of Henle, causing increased reabsorption of the percentage of sodium and chloride ions delivered to the ascending loop of Henle, thereby reducing the concentration of sodium chloride at the macula densa cells. This decrease in sodium chloride concentration initiates a signal from the macula densa that has two effects (Figure 27-11): (1) It decreases resistance to blood flow in the afferent arterioles, which raises glomerular hydrostatic pressure and helps return GFR toward normal, and (2) it increases renin release from the juxtaglomerular cells of the afferent and efferent arterioles, which are the major storage sites for renin. Renin released from these cells then functions as an enzyme to increase the formation of angiotensin I, which is converted to angiotensin II. Finally, the angiotensin II constricts the efferent arterioles, thereby increasing glomerular hydrostatic pressure and helping to return GFR toward normal. These two components of the tubuloglomerular feedback mechanism, operating together by way of the special anatomical structure of the juxtaglomerular apparatus, provide feedback signals to both the afferent and the efferent arterioles for efficient autoregulation of GFR during changes in arterial pressure. When both of these mechanisms are functioning together, the GFR changes only a few percentage points, even with large fluctuations in arterial pressure between the limits of 75 and 160 mm Hg.

Question 33

MYOGENIC AUTOREGULATION OF RENAL BLOOD FLOW AND GFR

Answer 33

Another mechanism that contributes to the maintenance of a relatively constant renal blood flow and GFR is the ability of individual blood vessels to resist stretching during increased arterial pressure, a phenomenon referred to as the myogenic mechanism. Studies of individual blood vessels (especially small arterioles) throughout the body have shown that they respond to increased wall tension or wall stretch by contraction of the vascular smooth muscle. Stretch of the vascular wall allows increased movement of calcium ions from the extracellular fluid into the cells, causing them to contract through the mechanisms discussed in Chapter 8. This contraction prevents excessive stretch of the vessel and at the same time, by raising vascular resistance, helps prevent excessive increases in renal blood flow and GFR when arterial pressure increases. Although the myogenic mechanism probably operates in most arterioles throughout the body, its importance in renal blood flow and GFR autoregulation has been questioned by some physiologists because this pressuresensitive mechanism has no means of directly detecting changes in renal blood flow or GFR per se. On the other hand, this mechanism may be more important in protecting the kidney from hypertension­induced injury. In response to sudden increases in blood pressure, the myogenic constrictor response in afferent arterioles occurs within seconds and therefore attenuates transmission of increased arterial pressure to the glomerular capillaries.

Question 34

High Protein Intake and Increased Blood Glucose Effect on kidney

Answer 34

Although renal blood flow and GFR are relatively stable under most conditions, there are circumstances in which these variables change significantly. For example, a high protein intake is known to increase both renal blood flow and GFR. With a long­term high­protein diet, such as one that contains large amounts of meat, the increases in GFR and renal blood flow are due partly to growth of the kidneys. However, GFR and renal blood flow also increase 20 to 30 percent within 1 or 2 hours after a person eats a high­protein meal. One likely explanation for the increased GFR is the following: A high­protein meal increases the release of amino acids into the blood, which are reabsorbed in the proximal tubule. Because amino acids and sodium are reabsorbed together by the proximal tubules, increased amino acid reabsorption also stimulates sodium reabsorption in the proximal tubules. This reabsorption of sodium decreases sodium delivery to the macula densa (see Figure 27-12), which elicits a tubuloglomerular feedback–mediated decrease in resistance of the afferent arterioles, as discussed earlier. The decreased afferent arteriolar resistance then raises renal blood flow and GFR. This increased GFR allows sodium excretion to be maintained at a nearly normal level while increasing the excretion of the waste products of protein metabolism, such as urea. A similar mechanism may also explain the marked increases in renal blood flow and GFR that occur with large increases in blood glucose levels in persons with uncontrolled diabetes mellitus. Because glucose, like some of the amino acids, is also reabsorbed along with sodium in the proximal tubule, increased glucose delivery to the tubules causes them to reabsorb excess sodium along with glucose. This reabsorption of excess sodium, in turn, decreases the sodium chloride concentration at the macula densa, activating a tubuloglomerular feedback–mediated dilation of the afferent arterioles and subsequent increases in renal blood flow and GFR. These examples demonstrate that renal blood flow and GFR per se are not the primary variables controlled by the tubuloglomerular feedback mechanism. The main purpose of this feedback is to ensure a constant delivery of sodium chloride to the distal tubule, where final processing of the urine takes place. Thus, disturbances that tend to increase reabsorption of sodium chloride at tubular sites before the macula densa tend to elicit increased renal blood flow and GFR, which helps return distal sodium chloride delivery toward normal so that normal rates of sodium and water excretion can be maintained (see Figure 27-12). An opposite sequence of events occurs when proximal tubular reabsorption is reduced. For example, when the proximal tubules are damaged (which can occur as a result of poisoning by heavy metals, such as mercury, or large doses of drugs, such as tetracyclines), their ability to reabsorb sodium chloride is decreased. As a consequence, large amounts of sodium chloride are delivered to the distal tubule and, without appropriate compensations, would quickly cause excessive volume depletion. One of the important compensatory responses appears to be a tubuloglomerular feedback–mediated renal vasoconstriction that occurs in response to the increased sodium chloride delivery to the macula densa in these circumstances. These examples again demonstrate the importance of this feedback mechanism in ensuring that the distal tubule receives the proper rate of delivery of sodium chloride, other tubular fluid solutes, and tubular fluid volume so that appropriate amounts of these substances are excreted in the urine.

Question 35

REGULATION OF FLUID EXCHANGE AND OSMOTIC EQUILIBRIUM BETWEEN INTRACELLULAR AND EXTRACELLULAR FLUID

Answer 35

The distribution of fluid between intracellular and extracellular compartments, in contrast, is determined mainly by the osmotic effect of the smaller solutes— especially sodium, chloride, and other electrolytes— acting across the cell membrane. The reason for this is that the cell membranes are highly permeable to water but relatively impermeable to even small ions such as sodium and chloride. Therefore, water moves across the cell membrane rapidly and the intracellular fluid remains isotonic with the extracellular fluid.

Question 36

Osmolarity of the Body Fluids

Answer 36

About 80 percent of the total osmolarity of the interstitial fluid and plasma is due to sodium and chloride ions, whereas for intracellular fluid, almost half the osmolarity is due to potassium ions and the remainder is divided among many other intracellular substances. As shown in Table 25-2, the total osmolarity of each of the three compartments is about 300 mOsm/L, with the plasma being about 1 mOsm/L greater than that of the interstitial and intracellular fluids. The slight difference between plasma and interstitial fluid is caused by the osmotic effects of the plasma proteins, which maintain about 20 mm Hg greater pressure in the capillaries than in the surrounding interstitial spaces.

Question 37

HOW OSMOTIC EQUILIBRIUM IS MAINTAINED BETWEEN INTRACELLULAR AND EXTRACELLULAR FLUIDS

Answer 37

Large osmotic pressures can develop across the cell
membrane with relatively small changes in the concentrations of solutes in the extracellular fluid. As discussed earlier, for each milliosmole concentration gradient of
an impermeant solute (one that will not permeate the cell membrane), about 19.3 mm Hg of osmotic pressure is exerted across the cell membrane. If the cell membrane is exposed to pure water and the osmolarity of intracellular fluid is 282 mOsm/L, the potential osmotic pressure that can develop across the cell membrane is more than 5400 mm Hg. This demonstrates the large force
that can move water across the cell membrane when the intracellular and extracellular fluids are not in osmotic equilibrium. As a result of these forces, relatively small changes in the concentration of impermeant solutes
in the extracellular fluid can cause large changes in cell volume.

Question 38

Isotonic, Hypotonic, and Hypertonic Fluids

Answer 38

The effects of different concentrations of impermeant solutes in the extracellular fluid on cell volume.

Question 39

Isosmotic, Hyperosmotic, and Hypo-Osmotic Fluids.

Answer 39

The terms isotonic, hypotonic, and hypertonic refer to whether solutions will cause a change in cell volume. The tonicity of solutions depends on the concentration of impermeant solutes. Some solutes, however, can permeate the cell membrane. Solutions with an osmolarity the same as the cell are called isosmotic, regardless of whether the solute can penetrate the cell membrane. The terms hyperosmotic and hypo-osmotic refer to solutions that have a higher or lower osmolarity, respectively, compared with the normal extracellular fluid, without regard for whether the solute permeates the
cell membrane. Highly permeating substances, such as urea, can cause transient shifts in fluid volume between the intracellular and extracellular fluids, but given enough time, the concentrations of these substances eventually become equal in the two compartments and have
little effect on intracellular volume under steady­state conditions.

Question 40

Renal pyramids

Answer 40

Their bases face the cortical-medullary border; the tip of each pyramid terminates in the renal pelvis. At the tip of each pyramid are perforations, almost invisible to the naked eye, through which urine fl ows into the minor calyces of the renal sinus.

Question 41

Lymph vessels of the kidney

Answer 41

They drain the interstitial fl uid of the cortex and may contain high concentrations of renal hormones such as erythropoietin (EPO), leave the kidney by following arteries toward the hilus. Lymphatics are absent from the renal medulla, where they would otherwise tend to drain the high-osmolality interstitial fl uid, which is necessary for producing concentrated urine

Question 42

A measure of glomerular filtration rate

Answer 42

The clearance of inulin.The ideal glomerular marker for measuring GFR would be a substance X that has the same concentration in the glomerular fi ltrate as in plasma and that also is not reabsorbed, secreted, synthesized, broken down, or accumulated by the tubules.

Px*GFR=Ux*V

Px*GFR=amount of X filtered

Ux*V=output of X into urine

Inulin is freely fi ltered at the glomerulus but is neither reabsorbed nor secreted by the renal tubules.

• the rate of inulin excretion (UIn * V ) is directly proportional to the plasma inulin concentration.
• inulin clearance is independent of the plasma inulin concentration
• inulin clearance is independent of urine flow

Question 43

The clearance of creatinine is a useful clinical index of what?

Answer 43

Glomerular fi ltration rate

Tubules, to variable degree, secrete creatinine, which, by itself, would lead to an ~20% overestimate of GFR in humans. However, because commonly used colorimetric methods overestimate plasma creatinine concentrations, the calculated creatinine clearance turns out to be close to the inulin clearance. Thus, the effects of these two errors (i.e., tubule secretion and overestimated plasma levels) tend to cancel out each other. to avoid errors in estimating the GFR from the creatinine clearance, one must take care to exclude non–steady-state pathologic conditions of creatinine release, such as hyperthermia or other conditions of muscle wasting or damage. Ingestion of meat, which has a high creatinine content, also produces non–steady-state conditions. To minimize the effects of such an ingestion, the patient collects urine over an entire 24-hour period, and the plasma sample is obtained by venipuncture in the morning before breakfast.

Question 44

Sieving coefficient

Answer 44

The ratio of solute concentration in the ultrafiltrate versus the plasma (UFX/PX). low molecular weight (<5500 Da) and small effective molecular radius (e.g., water, urea, glucose, and inulin) appear in the fi ltrate in the same concentration as in plasma (UFX/PX = 1). In these instances, no sieving of the contents of the fl uid
moving through the glomerular “pores” occurs, so that the water moving through the fi ltration slits by convection carries the solutes with it. As a result, the concentration of the solute in the fi ltrate is the same as in bulk plasma. The situation is different for substances with a molecular weight that is greater than ~14 kDa, such as lysozyme. Larger and larger macromolecules are increasingly restricted from passage, so that only traces of plasma albumin (69 kDa) are normally present in the glomerular filtrate.

Question 45

Filtration equilibrium

Answer 45

When opposing forces along the glomerular capillary cancel out each other, and no further filtration occurs.At low glomerular plasma flow filtration equilibrium occurs halfway down the capillary.

Question 46

Plasma osmolarity can be estimated from?

Answer 46

Plasma Na+ concentration, plasma glucose concentration, and blood urea nitrogen (BUN), as these are the major solutes of ECF and plasma.

Plasma osmolarity =2xPlasma Na+Glucose/18+BUN/2.8

The Na+ concentration is multiplied by 2 because Na+ must be balanced by an equal concentration of anions. (In plasma, these anions are Cl− and HCO3−.)

Question 47

Isosmotic Volume Contraction

Answer 47

A person with diarrhea loses a large volume of fluid from the gastrointestinal tract. The osmolarity of the fluid lost is approximately equal to that of the ECF—it is isosmotic. Thus the disturbance in diarrhea is loss of isosmotic fluid from ECF. As a result, ECF volume decreases, but there is no accompanying change in ECF osmolarity (because the fluid that was lost is isosmotic). Because there is no change in ECF osmolarity, there is no need for a fluid shift across cell membranes and ICF volume remains unchanged. In the new steady state, ECF volume decreases and the osmolarities of ECF and ICF are unchanged. The decrease in ECF volume means that blood volume (a component of ECF) also is reduced, which produces a decrease in arterial pressure. Other consequences of diarrhea include increased hematocrit and increased plasma protein concentration, which are explained by the loss of isosmotic fluid from the ECF compartment. The red blood cells and proteins that remain behind in the vascular component of the ECF are concentrated by this fluid loss.

Question 48

Hyperosmotic Volume Contraction

Answer 48

Water Deprivation A person who is lost in the desert without adequate drinking water loses both NaCl and water in sweat. A key piece of information, not immediately obvious, is that sweat is hyposmotic relative to ECF; that is, compared with the body fluids, sweat contains relatively more water than solute. Because hyposmotic fluid is lost from the ECF, ECF volume decreases and ECF osmolarity increases. ECF osmolarity is transiently higher than ICF osmolarity, and this difference in osmolarity causes water to shift from ICF into ECF. Water will flow until ICF osmolarity increases and becomes equal to ECF osmolarity. This shift of water out of cells decreases ICF volume. In the new steady state, both ECF and ICF volumes will be decreased and ECF and ICF osmolarities will be increased and equal to each other. In hyperosmotic volume contraction, the plasma protein concentration is increased but the hematocrit is unchanged. The explanation for the increase in plasma protein concentration is straightforward: Fluid is lost from ECF, and the plasma protein remaining behind becomes concentrated. It is less obvious, however, why the hematocrit is unchanged. Loss of fluid from ECF alone would cause an increase in the “concentration” of red blood cells and an increase in hematocrit. However, there also is a fluid shift in this disturbance: Water moves from ICF to ECF. Because red blood cells are cells, water shifts out of them, decreasing their volume. Thus the concentration of red blood cells increases, but red blood cell volume decreases. The two opposite effects offset each other, and hematocrit is unchanged. What is the final state of the ECF volume? Is it decreased (because of the loss of ECF volume in sweat), increased (because of the water shift from ICF to ECF), or unchanged (because both occur)? Answer: ECF volume is lower than normal.

Question 49

Hyposmotic Volume Contraction

Answer 49

Adrenal Insufficiency A person with adrenal insufficiency has a deficiency of several hormones including aldosterone, a hormone that normally promotes Na+ reabsorption in the distal tubule and collecting ducts. As a result of aldosterone deficiency, excess NaCl is excreted in the urine. Because NaCl is an ECF solute, ECF osmolarity decreases. Transiently, ECF osmolarity is less than ICF osmolarity, which causes water to shift from ECF to ICF until ICF osmolarity decreases to the same level as ECF osmolarity. In the new steady state, both ECF and ICF osmolarities will be lower than normal and equal to each other. Because of the shift of water, ECF volume will be decreased and ICF volume will be increased. In hyposmotic volume contraction, both plasma protein concentration and hematocrit will be increased because of the decrease in ECF volume. Hematocrit increases also because of the shift of water into red blood cells, increasing cell volume.

Question 50

Isosmotic Volume Expansion

Answer 50

Infusion of NaCl A person who receives an infusion of isotonic NaCl presents the opposite clinical picture of the person who has lost isotonic fluid through diarrhea. Because NaCl is an extracellular solute, all of the isotonic NaCl solution is added to the ECF, causing an increase in ECF volume but no change in ECF osmolarity. There will be no shift of water between ICF and ECF because there is no difference in osmolarity between the two compartments. Both plasma protein concentration and hematocrit will decrease (i.e., be diluted) because of the increase in ECF volume.

Question 51

Hyperosmotic Volume Expansion

Answer 51

Ingesting dry NaCl (e.g., eating a bag of potato chips) will increase the total amount of solute in the ECF. As a result, ECF osmolarity increases. Transiently, ECF osmolarity is higher than ICF osmolarity, which causes water to shift from ICF to ECF, decreasing ICF volume and increasing ECF volume. In the new steady state, both ECF and ICF osmolarities will be higher than normal and equal to each other. Because of the shift of water out of cells, ICF volume will decrease and ECF volume will increase. In hyperosmotic volume expansion, both plasma protein concentration and hematocrit will decrease due to the increase in ECF volume. Hematocrit also will be decreased because of the water shift out of the red blood cells.

Question 52

Hyposmotic Volume Expansion

Answer 52

A person with syndrome of inappropriate antidiuretic hormone (SIADH) secretes inappropriately high levels of antidiuretic hormone (ADH), which promotes water reabsorption in the collecting ducts. When ADH levels are abnormally high, too much water is reabsorbed and the excess water is retained and distributed throughout the total body water. The volume of water that is added to ECF and ICF is in direct proportion to their original volumes. For example, if an extra 3 L of water is reabsorbed by the collecting ducts, 1 L will be added to the ECF and 2 L will be added to the ICF (because ECF constitutes one-third and ICF constitutes two-thirds of the total body water). When compared with the normal state, ECF and ICF volumes will be increased and ECF and ICF osmolarities will be decreased. In hyposmotic volume expansion, plasma protein concentration is decreased by dilution. However, the hematocrit is unchanged as a result of two offsetting effects: The concentration of red blood cells decreases because of dilution, but red blood cell volume increases because water shifts into the cells.

Question 53

The major mechanism for changing blood flow in the kidney?

Answer 53

By changing arteriolar resistance. In the kidney, this can be accomplished by changing afferent arteriolar resistance and/or efferent arteriolar resistance.

Q = ΔP/R

Question 54

Prostaglandins in kidney.

Answer 54

The same stimuli that activate the sympathetic nervous system and increase angiotensin II levels in hemorrhage also activate local renal prostaglandin production. Although these actions may seem contradictory, the vasodilatory effects of prostaglandins are clearly protective for RBF. Thus prostaglandins attenuate the vasoconstriction produced by the sympathetic nervous system and angiotensin II. Unopposed, this vasoconstriction can cause a profound reduction in RBF, resulting in renal failure.

Question 55

Autoregulation of Renal Blood Flow

Answer 55

For renal autoregulation, it is believed that resistance is controlled primarily at the level of the afferent arteriole, rather than the efferent arteriole.

Myogenic hypothesis. The myogenic hypothesis states that increased arterial pressure stretches the blood vessels, which causes reflex contraction of smooth muscle in the blood vessel walls and consequently increased resistance to blood flow (see Chapter 4). The mechanism of stretch-induced contraction involves the opening of stretch-activated calcium (Ca2+) channels in the smooth muscle cell membranes. When these channels are open, more Ca2+ enters vascular smooth muscle cells, leading to more tension in the blood vessel wall. The myogenic hypothesis explains autoregulation of RBF as follows: Increases in renal arterial pressure stretch the walls of the afferent arterioles, which respond by contracting. Afferent arteriolar contraction leads to increased afferent arteriolar resistance. The increase in resistance then balances the increase in arterial pressure, and RBF is kept constant.

Tubuloglomerular feedback

When renal arterial pressure increases, both RBF and GFR increase. The increase in GFR results in increased delivery of solute and water to the macula densa region of the early distal tubule, which senses some component of the increased delivered load. The macula densa, which is a part of the juxtaglomerular apparatus, responds to the increased delivered load by secreting a vasoactive substance that constricts afferent arterioles via a paracrine mechanism (adenosine). Local vasoconstriction of afferent arterioles then reduces RBF and GFR back to normal;

Question 56

Markers for Glomerular Filtration Rate

Answer 56

Both blood urea nitrogen (BUN) and serum creatinine concentration can be used to estimate GFR because both urea and creatinine are filtered across the glomerular capillaries. Thus each substance depends

on the filtration step in order to be excreted in urine. When there is a decrease in GFR (e.g., in renal failure), BUN and serum creatinine increase because they are not adequately filtered. Volume contraction (hypovolemia) results in decreased renal perfusion and, as a consequence, decreased GFR (prerenal azotemia). In prerenal azotemia, both BUN and serum creatinine are increased due to the decrease in GFR. However, because urea is reabsorbed and creatinine is not, BUN increases more than serum creatinine; in volume contraction, there
is increased proximal reabsorption of all solutes, including urea, which is responsible for the greater increase in BUN. One indicator, therefore, of volume contraction (prerenal azotemia) is an increased ratio of BUN/creatinine to more than 20. In contrast, renal failure due to renal causes (e.g., chronic renal failure) produces an increase in both BUN and serum creatinine, but it does not produce an increase in the ratio of BUN/creatinine.