Urinary System
56. Functions of the kidneys in homeostasis. Physiological anatomy of the kidneys – the nephron as a
functional unit of the kidney. Renal blood supply. Glomerular filtration - the first step in urine formation.
Physiological control of glomerular filtration.
57. Urine formation. Reabsorption and secretion along different parts of the nephron.
58. Regulation of tubular reabsorption. Glomerulotubular balance.
Hormonal control of tubular reabsorption.
59. Urine concentration and dilution. Micturition. Use of clearance methods to quantify kidney function.
60. Body fluid compartments. Balance of fluid intake and output.
Regulation of extracellular fluid composition (ionic composition) and volume.
61. Regulation of acid - base balance. The chemical acid - base buffer systems of the body fluids.
Respiratory and renal control of acid - base balance.
56. Function of kidney in homeostasis. Physiological anatomy of the kidney- the nephron as a
functional unit of the kidney. Renal blood supply. Glomerular filtration-the first step of urine formation.
Physiological control of glomerular filtration
Multiple Functions of the Kidneys
Most people are familiar with one important function of the kidneys-to rid the body of waste materials that
are either ingested or produced by metabolism. A second function that is especially critical is to control the
volume and composition of the body fluids. For water and virtually all electrolytes in the body, the balance
between intake (due to ingestion or metabolic production) and output (due to excretion or metabolic
consumption) is maintained largely by the kidneys. This regulatory function of the kidneys maintains the
stable internal environment necessary for the cells to perform their various activities.
The kidneys perform their most important functions by filtering the plasma and removing substances from
the filtrate at variable rates, depending on the needs of the body. Ultimately, the kidneys "clear" unwanted
substances from the filtrate (and therefore from the blood) by excreting them in the urine while returning
substances that are needed back to the blood. Although this chapter and the next few chapters focus
mainly on the control of renal excretion of water, electrolytes, and metabolic waste products, the kidneys
serve many important homeostatic functions, including the following:
• Excretion of metabolic waste products and foreign
chemicals
• Regulation of water and electrolyte balances
• Regulation of body fluid osmolality and electrolyte
concentrations
• Regulation of arterial pressure
• Regulation of acid-base balance
• Secretion, metabolism, and excretion of hormones
• Gluconeogenesis
Regulation of 1,25-Dihydroxyvitamin D3 Production The
kidneys produce the active form of vitamin D, 1,25-
dihydroxyvitamin D3 (calcitriol), by hydroxylating this vitamin
at the "number 1" position. Calcitriol is essential for normal
calcium deposition in bone and calcium reabsorption by the
gastrointestinal tract. As discussed in Chapter 79, calcitriol
plays an important role in calcium and phosphate regulation.
Physiological anatomy of the kidney- the nephron as a functional unit of the kidney.
The renal circulation is unique in having two capillary beds, the glomerular and peritubular capillaries, which
are arranged in series and separated by the efferent arterioles, which help regulate the hydrostatic
pressure in both sets of capillaries. High hydrostatic pressure in the glomerular capillaries (about 60 mm
Hg) causes rapid fluid filtration, whereas a much lower hydrostatic pressure in the peritubular capillaries
(about 13 mm Hg) permits rapid fluid reabsorption. By adjusting the resistance of the afferent and efferent
arterioles, the kidneys can regulate the hydrostatic pressure in both the glomerular and the peritubular
1
,capillaries, thereby changing the rate of glomerular filtration, tubular reabsorption, or both in response to
body homeostatic demands.
The peritubular capillaries empty into the vessels of the venous system, which run parallel to the arteriolar
vessels. The blood vessels of the venous system progressively form the interlobular vein, arcuate vein,
interlobar vein, and renal vein, which leaves the kidney beside the renal artery and ureter.
The Nephron Is the Functional Unit of the Kidney
Each kidney in the human contains about 800,000 to 1,000,000 nephrons, each capable of forming urine.
The kidney cannot regenerate new nephrons. Therefore, with renal injury, disease, or normal aging, there
is a gradual decrease in nephron number. After age 40, the number of functioning nephrons usually
decreases about 10 percent every 10 years; thus, at age 80, many people have 40 percent fewer
functioning nephrons than they did at age 40. This loss is not life threatening because adaptive changes in
the remaining nephrons allow them to excrete the proper amounts of water, electrolytes, and waste
products, as discussed in Chapter 31. Each nephron contains (1) a tuft of glomerular capillaries called the
glomerulus, through which large amounts of fluid are filtered from the blood, and (2) a long tubule in which
the filtered fluid is converted into urine on its way to the pelvis of the kidney (see Figure 26-3).
Renal Blood Flow
In an average 70-kilogram man, the combined blood flow
through both kidneys is about 1100 ml/min, or about 22
percent of the cardiac output. Considering that the two
kidneys constitute only about 0.4 percent of the total body
weight, one can readily see that they receive an extremely
high blood flow compared with other organs. As with other
tissues, blood flow supplies the kidneys with nutrients and
removes waste products. However, the high flow to the
kidneys greatly exceeds this need. The purpose of this
additional flow is to supply enough plasma for the high
rates of glomerular filtration that are necessary for precise
regulation of body fluid volumes and solute concentrations.
As might be expected, the mechanisms that regulate renal
blood flow are closely linked to the control of GFR and the
excretory functions of the kidneys. Blood Flow in the Vasa
Recta of the Renal Medulla Is Very Low Compared with
Flow in the Renal Cortex. The outer part of the kidney, the renal cortex, receives most of the kidney's blood
flow. Blood flow in the renal medulla accounts for only 1 to 2 percent of the total renal blood flow. Flow to
the renal medulla is supplied by a specialized portion of the peritubular capillary system called the vasa
recta. These vessels descend into the medulla in parallel with the loops of Henle and then loop back along
with the loops of Henle and return to the cortex before emptying into the venous system. As discussed in
Chapter 28, the vasa recta play an important role in allowing the kidneys to form concentrated urine.
2
, Glomerular Filtration-the First Step in Urine Formation
Composition of the Glomerular Filtrate, Urine formation begins with filtration of large amounts of fluid
through the glomerular capillaries into Bowman's capsule. 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.
GFR Is About 20 Percent of the Renal Plasma Flow; As in other capillaries, the GFR is determined by (1)
the balance of hydrostatic and colloid osmotic forces acting across the capillary membrane and (2) the
capillary filtration coefficient (Kf), the product of the permeability and filtering surface area of the capillaries.
The glomerular capillaries have a much higher rate of filtration than most other capillaries because of a high
glomerular hydrostatic pressure and a large Kf. In the average adult human, the GFR is about 125 ml/min,
or 180 L/day. The fraction of the renal plasma flow that is filtered (the filtration fraction) averages about 0.2;
this means that about 20 percent of the plasma flowing through the kidney is filtered through the glomerular
capillaries. The filtration fraction is calculated as follows: Filtration fraction = Gfr/Renal plasma flow.
Physiologic Control of Glomerular Filtration and Renal Blood Flow
The determinants of GFR that are most variable and subject to physiologic control include the glomerular
hydrostatic pressure and the glomerular capillary colloid osmotic pressure. These variables, in turn, are
influenced by the sympathetic nervous system, hormones and autacoids (vasoactive substances that are
released in the kidneys and act locally), and other feedback controls that are intrinsic to the kidneys.
Sympathetic Nervous System Activation Decreases GFR
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.
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.
Hormonal and Autacoid Control of Renal Circulation
Several hormones and autacoids can influence GFR and renal blood flow, as summarized in Table 26-4.
Norepinephrine, Epinephrine, and Endothelin Constrict Renal Blood Vessels and Decrease GFR Hormones
that constrict afferent and efferent arterioles, causing reductions in GFR and renal blood flow, include
norepinephrine and epinephrine released from the adrenal medulla. In general, blood levels of these
hormones parallel the activity of the sympathetic nervous system; thus, norepinephrine and epinephrine
have little influence on renal hemodynamics except under extreme conditions, such as severe hemorrhage.
Another vasoconstrictor, endothelin, is a peptide that can be released by damaged vascular endothelial
cells of the kidneys, as well as by other tissues. The physiologic role of this autacoid is not completely
understood.
3
56. Functions of the kidneys in homeostasis. Physiological anatomy of the kidneys – the nephron as a
functional unit of the kidney. Renal blood supply. Glomerular filtration - the first step in urine formation.
Physiological control of glomerular filtration.
57. Urine formation. Reabsorption and secretion along different parts of the nephron.
58. Regulation of tubular reabsorption. Glomerulotubular balance.
Hormonal control of tubular reabsorption.
59. Urine concentration and dilution. Micturition. Use of clearance methods to quantify kidney function.
60. Body fluid compartments. Balance of fluid intake and output.
Regulation of extracellular fluid composition (ionic composition) and volume.
61. Regulation of acid - base balance. The chemical acid - base buffer systems of the body fluids.
Respiratory and renal control of acid - base balance.
56. Function of kidney in homeostasis. Physiological anatomy of the kidney- the nephron as a
functional unit of the kidney. Renal blood supply. Glomerular filtration-the first step of urine formation.
Physiological control of glomerular filtration
Multiple Functions of the Kidneys
Most people are familiar with one important function of the kidneys-to rid the body of waste materials that
are either ingested or produced by metabolism. A second function that is especially critical is to control the
volume and composition of the body fluids. For water and virtually all electrolytes in the body, the balance
between intake (due to ingestion or metabolic production) and output (due to excretion or metabolic
consumption) is maintained largely by the kidneys. This regulatory function of the kidneys maintains the
stable internal environment necessary for the cells to perform their various activities.
The kidneys perform their most important functions by filtering the plasma and removing substances from
the filtrate at variable rates, depending on the needs of the body. Ultimately, the kidneys "clear" unwanted
substances from the filtrate (and therefore from the blood) by excreting them in the urine while returning
substances that are needed back to the blood. Although this chapter and the next few chapters focus
mainly on the control of renal excretion of water, electrolytes, and metabolic waste products, the kidneys
serve many important homeostatic functions, including the following:
• Excretion of metabolic waste products and foreign
chemicals
• Regulation of water and electrolyte balances
• Regulation of body fluid osmolality and electrolyte
concentrations
• Regulation of arterial pressure
• Regulation of acid-base balance
• Secretion, metabolism, and excretion of hormones
• Gluconeogenesis
Regulation of 1,25-Dihydroxyvitamin D3 Production The
kidneys produce the active form of vitamin D, 1,25-
dihydroxyvitamin D3 (calcitriol), by hydroxylating this vitamin
at the "number 1" position. Calcitriol is essential for normal
calcium deposition in bone and calcium reabsorption by the
gastrointestinal tract. As discussed in Chapter 79, calcitriol
plays an important role in calcium and phosphate regulation.
Physiological anatomy of the kidney- the nephron as a functional unit of the kidney.
The renal circulation is unique in having two capillary beds, the glomerular and peritubular capillaries, which
are arranged in series and separated by the efferent arterioles, which help regulate the hydrostatic
pressure in both sets of capillaries. High hydrostatic pressure in the glomerular capillaries (about 60 mm
Hg) causes rapid fluid filtration, whereas a much lower hydrostatic pressure in the peritubular capillaries
(about 13 mm Hg) permits rapid fluid reabsorption. By adjusting the resistance of the afferent and efferent
arterioles, the kidneys can regulate the hydrostatic pressure in both the glomerular and the peritubular
1
,capillaries, thereby changing the rate of glomerular filtration, tubular reabsorption, or both in response to
body homeostatic demands.
The peritubular capillaries empty into the vessels of the venous system, which run parallel to the arteriolar
vessels. The blood vessels of the venous system progressively form the interlobular vein, arcuate vein,
interlobar vein, and renal vein, which leaves the kidney beside the renal artery and ureter.
The Nephron Is the Functional Unit of the Kidney
Each kidney in the human contains about 800,000 to 1,000,000 nephrons, each capable of forming urine.
The kidney cannot regenerate new nephrons. Therefore, with renal injury, disease, or normal aging, there
is a gradual decrease in nephron number. After age 40, the number of functioning nephrons usually
decreases about 10 percent every 10 years; thus, at age 80, many people have 40 percent fewer
functioning nephrons than they did at age 40. This loss is not life threatening because adaptive changes in
the remaining nephrons allow them to excrete the proper amounts of water, electrolytes, and waste
products, as discussed in Chapter 31. Each nephron contains (1) a tuft of glomerular capillaries called the
glomerulus, through which large amounts of fluid are filtered from the blood, and (2) a long tubule in which
the filtered fluid is converted into urine on its way to the pelvis of the kidney (see Figure 26-3).
Renal Blood Flow
In an average 70-kilogram man, the combined blood flow
through both kidneys is about 1100 ml/min, or about 22
percent of the cardiac output. Considering that the two
kidneys constitute only about 0.4 percent of the total body
weight, one can readily see that they receive an extremely
high blood flow compared with other organs. As with other
tissues, blood flow supplies the kidneys with nutrients and
removes waste products. However, the high flow to the
kidneys greatly exceeds this need. The purpose of this
additional flow is to supply enough plasma for the high
rates of glomerular filtration that are necessary for precise
regulation of body fluid volumes and solute concentrations.
As might be expected, the mechanisms that regulate renal
blood flow are closely linked to the control of GFR and the
excretory functions of the kidneys. Blood Flow in the Vasa
Recta of the Renal Medulla Is Very Low Compared with
Flow in the Renal Cortex. The outer part of the kidney, the renal cortex, receives most of the kidney's blood
flow. Blood flow in the renal medulla accounts for only 1 to 2 percent of the total renal blood flow. Flow to
the renal medulla is supplied by a specialized portion of the peritubular capillary system called the vasa
recta. These vessels descend into the medulla in parallel with the loops of Henle and then loop back along
with the loops of Henle and return to the cortex before emptying into the venous system. As discussed in
Chapter 28, the vasa recta play an important role in allowing the kidneys to form concentrated urine.
2
, Glomerular Filtration-the First Step in Urine Formation
Composition of the Glomerular Filtrate, Urine formation begins with filtration of large amounts of fluid
through the glomerular capillaries into Bowman's capsule. 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.
GFR Is About 20 Percent of the Renal Plasma Flow; As in other capillaries, the GFR is determined by (1)
the balance of hydrostatic and colloid osmotic forces acting across the capillary membrane and (2) the
capillary filtration coefficient (Kf), the product of the permeability and filtering surface area of the capillaries.
The glomerular capillaries have a much higher rate of filtration than most other capillaries because of a high
glomerular hydrostatic pressure and a large Kf. In the average adult human, the GFR is about 125 ml/min,
or 180 L/day. The fraction of the renal plasma flow that is filtered (the filtration fraction) averages about 0.2;
this means that about 20 percent of the plasma flowing through the kidney is filtered through the glomerular
capillaries. The filtration fraction is calculated as follows: Filtration fraction = Gfr/Renal plasma flow.
Physiologic Control of Glomerular Filtration and Renal Blood Flow
The determinants of GFR that are most variable and subject to physiologic control include the glomerular
hydrostatic pressure and the glomerular capillary colloid osmotic pressure. These variables, in turn, are
influenced by the sympathetic nervous system, hormones and autacoids (vasoactive substances that are
released in the kidneys and act locally), and other feedback controls that are intrinsic to the kidneys.
Sympathetic Nervous System Activation Decreases GFR
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.
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.
Hormonal and Autacoid Control of Renal Circulation
Several hormones and autacoids can influence GFR and renal blood flow, as summarized in Table 26-4.
Norepinephrine, Epinephrine, and Endothelin Constrict Renal Blood Vessels and Decrease GFR Hormones
that constrict afferent and efferent arterioles, causing reductions in GFR and renal blood flow, include
norepinephrine and epinephrine released from the adrenal medulla. In general, blood levels of these
hormones parallel the activity of the sympathetic nervous system; thus, norepinephrine and epinephrine
have little influence on renal hemodynamics except under extreme conditions, such as severe hemorrhage.
Another vasoconstrictor, endothelin, is a peptide that can be released by damaged vascular endothelial
cells of the kidneys, as well as by other tissues. The physiologic role of this autacoid is not completely
understood.
3
