Renal Functions, Basic

Processes, and Anatomy 1

OBJECTIVES
Y State 8 major functions of the kidneys.
Y Define the balance concept.
Y Define the gross structures and their interrelationships: renal pelvis, calyces, renal
pyramids, renal medulla (inner and outer zones), renal cortex, and papilla.
Y Define the components of the nephron-collecting duct system and their
interrelationships: renal corpuscle, glomerulus, tubule, and collecting-duct system.
Y Draw the relationship between glomerulus, Bowman’s capsule, and the proximal
tubule.
Y Define juxtaglomerular apparatus and describe its 3 cell types; state the function
of the granular cells.
Y List the individual tubular segments in order; state the segments that comprise the
proximal tubule, Henle’s loop, and the collecting-duct system; define principal
cells and intercalated cells.
Y Define the basic renal processes: glomerular filtration, tubular reabsorption,
and tubular secretion.
Y Define renal metabolism of a substance and give examples.

RENAL FUNCTIONS
The kidneys are traditionally known as organs that excrete waste. Although
they do indeed excrete waste, they also perform a spectrum of other functions
essential for health such as assuring bone integrity and helping to maintain
blood pressure. As they carry out these functions the kidneys work cooperatively
and interactively with other organ systems, particularly the cardiovascular sys-
tem. This chapter provides a brief account of renal functions and an overview
of how the kidneys perform them, and a description of essential renal anatomy.
Ensuing chapters delve into specific renal mechanisms and their interactions
with other organ systems.

1
2 / CHAPTER 1

Function 1: Excretion of Metabolic Waste and Foreign Substances

Our bodies continuously form end products of metabolic processes. In
most cases, those end products are of no use to the body and are harmful
at high concentrations. fterefore, they must be excreted at the same rate
as they are produced. Some of these products include urea (from protein), uric acid
(from nucleic acids), creatinine (from muscle creatine), urobilin (an end product of
hemoglobin breakdown that gives urine much of its color), and the metabolites of
various hormones. In addition, foreign substances, including many common
drugs, are excreted by the kidneys. In many cases the kidneys work in partnership
with the liver. fte liver metabolizes many organic molecules into water-soluble
forms that are more easily handled by the kidneys.

Function 2: Regulation of Water and Electrolyte Balance

Water, salt, and other electrolytes enter our bodies at highly variable rates,
all of which perturb the amount and concentration of those substances in
the body. fte kidneys vary their excretion of electrolytes and water to
preserve appropriate levels in the body. In doing so they maintain balance, that is,
match output to input so as to keep a constant amount in the body. As an exam-
ple, consider water balance. Our input of water is sporadic and only rarely driven
in response to body needs. We drink water when thirsty, but we also drink water
because it is a component of beverages that we consume for reasons other than
hydration. In addition, solid food often contains large amounts of water. fte kid-
neys respond to increases in water content by increasing the output of water in the
urine, thereby restoring body water to normal levels. fte same principles apply to
an array of electrolytes and other substances that have variable inputs.
Besides excreting excess amounts of various substances, the kidneys respond to
deficits. Although the kidneys cannot generate lost water or electrolytes, they can
reduce output to a minimum, thus preserving body stores. One of the feats of the
kidneys is their ability to regulate
each of these substances indepen-
Excretion of waste is only one dently. Within limits we can be on a
of many necessary functions high-sodium, low-potassium diet or
performed by the kidneys. low-sodium, high-potassium diet,
and the kidneys adjust excretion of
each of these substances appropri-
ately. The reader should also be aware that being in balance for a substance does
not by itself imply a normal state or good health. A person may have an excess or
deficit of a substance, yet still be in balance so long as output matches input. This
is often the case in chronic disorders of renal function or metabolism.

Function 3: Regulation of Extracellular Fluid Volume

The kidneys work in partnership with cardiovascular system, each one performing
a service for the other. By far the most important task of the kidneys in this regard
is to maintain extracellular fluid volume, of which blood plasma is a significant
 RENAL FUNCTIONS, BASIC PROCESSES, AND ANATOMY / 3

component. This ensures that the vascular space is filled with sufficient volume so
that blood can circulate normally. Maintenance of extracellular fluid volume is a
result of water and salt balance described above.

Function 4: Regulation of Plasma Osmolality

Another major aspect of water and electrolyte balance is the regulation
of plasma osmolality, that is, the summed concentration of dissolved
solutes. Osmolality is altered whenever the inputs and outputs of water
and dissolved solutes change disproportionately, as when drinking pure water or
eating a salty meal. Not only must the kidneys excrete water and solutes to
match inputs, they must do so at rates that keep the ratio of solutes and water at
a nearly constant value.

Function 5: Regulation of Red Blood Cell Production

Red blood cell production by the bone marrow is stimulated by the peptide hor-
mone erythropoietin. During embryological development erythropoietin is pro-
duced by the liver, but in the adult its major source is the kidneys. The renal cells
that secrete it are a particular group of interstitial cells in the cortical interstitium
near the border between the renal cortex and medulla (see later). The stimulus for
its secretion is a reduction in the partial pressure of oxygen in the local environ-
ment of the secreting cells. Although renal blood flow is large, renal metabolism
is also large and local oxygenation drops in cases of anemia, which can be caused
by blood loss, arterial hypoxia, or inadequate renal blood flow. These conditions
all stimulate secretion of erythropoietin. However in chronic renal failure, renal
metabolism falls, resulting in lower oxygen consumption and therefore higher
local tissue oxygenation. This “fools” the erythropoietin-secreting cells into
diminished erythropoietin secretion. The ensuing decrease in bone marrow activ-
ity is one important causal factor of anemia associated with chronic renal disease.

Function 6: Regulation of Vascular Resistance

Besides their major role in ensuring adequate volume for the cardiovascular sys-
tem, the kidneys also participate in the production of vasoactive substances (via
the renin-angiotensin-aldosterone system described later) that exert major control
over vascular smooth muscle. In turn, this influences peripheral vascular resis-
tance and therefore systemic arterial blood pressure. Pathology in this aspect of
renal function leads to hypertension.

Function 7: Regulation of Acid-base Balance

Acids and bases enter the body fluids via ingestion and from metabolic processes.
The body has to excrete acids and bases to maintain balance and it also has to
regulate the concentration of free hydrogen ions (pH) within a limited range. The
kidneys accomplish both tasks by a combination of elimination and synthesis.
These interrelated tasks are among the most complicated aspects of renal function
and will be explored thoroughly in Chapter 9.
4 / CHAPTER 1

Function 8: Regulation of Vitamin D Production

When we think of vitamin D, we often think of sunlight or additives to
milk. In vivo vitamin D synthesis involves a series of biochemical transforma-
tions, the last of which occurs in the kidneys. The active form of vitamin D
(1,25-dihydroxyvitamin D), called calcitriol, is actually made in the kidneys, and
its rate of synthesis is regulated by hormones that control calcium and phosphate
balance and bone integrity, which will be discussed in detail in Chapter 10.

Function 9: Gluconeogenesis
Our central nervous system is an obligate user of blood glucose regardless of
whether we have just eaten sugary doughnuts or gone without food for a week.
Whenever the intake of carbohydrate is stopped for much more than half a day,
our body begins to synthesize new glucose (the process of gluconeogenesis) from
noncarbohydrate sources (amino acids from protein and glycerol from triglycer-
ides). Most gluconeogenesis occurs in the liver, but a substantial fraction occurs in
the kidneys, particularly during a prolonged fast.

OVERVIEW OF RENAL PROCESSES

Most of what the kidneys actually do is conceptually speaking fairly straightfor-
ward. Of the considerable volume of plasma entering the kidneys each minute from
the renal arteries, they transfer (by filtration) about one fifth of it, minus the larger
plasma proteins, into the renal tubules. They then selectively reabsorb varying frac-
tions of the filtered substances back into the blood, leaving the unreabsorbed por-
tions to be excreted. In some cases additional amounts are added to the excreted
content by secretion or synthesis. There is a division of labor between different
regions of the tubules for carrying out these tasks that depends on the type of cell
expressed in a given region. In essence, the renal tubules operate like assembly lines;
they accept the fluid coming into them, perform some segment-specific modifica-
tion of the fluid, and send it on to the next segment. The final product (urine)
contains amounts of each substance that maintain balance for each of them.

ANATOMY OF THE KIDNEYS AND URINARY SYSTEM

fte kidneys are bean-shaped organs about the size of a fist. ftey are
located just under the rib cage behind the peritoneal cavity close to the
posterior abdominal wall, one on each side of the vertebral column
(Figure 1–1). fte rounded, outer convex surface of each kidney faces the side of
the body, and the indented surface, called the hilum, faces the spine. Each hilum
is penetrated by blood vessels, nerves, and a ureter. fte ureters bend down and
travel a considerable distance to the bladder. Each ureter within a kidney is
formed from several funnel-like structures called major calyces, which are them-
selves formed from minor calyces. fte minor calyces fit over underlying cone-
shaped renal tissue called pyramids. fte tip of each pyramid is called a papilla
and projects into a minor calyx. fte calyces act as collecting cups for the urine
 RENAL FUNCTIONS, BASIC PROCESSES, AND ANATOMY / 5

Diaphragm

Kidney

Ureter

Bladder

Urethra

Figure 1–1. Urinary system in a female, indicating the location of the kidneys below the
diaphragm and well above the bladder, which is connected to the kidneys via the ure-
ters. (Reproduced with permission from Widmaier EP, Raff H, Strang KT. Vander’s Human
Physiology. 11th ed. McGraw-Hill; 2008.)

formed by the renal tissue in the pyramids. fte pyramids are arranged radially
around the hilum, with the papillae pointing toward the hilum and the broad
bases of the pyramids facing the convex surface of the kidney. fte pyramids
constitute the medulla of the kidney. Overlying the medullary tissue is a cortex,
and covering the cortical tissue on the very external surface of the kidney is a thin
connective tissue capsule (Figure 1–2).
The working tissue mass of both the cortex and medulla is constructed almost
entirely of tubules (nephrons and collecting tubules) and blood vessels (capillaries
and capillary-like vessels). Between the tubules and blood vessels is the intersti-
tium, which comprises less than 10% of the renal volume. It contains a small
amount of interstitial fluid and scattered interstitial cells (fibroblasts and others)
that synthesize an extracellular matrix of collagen, proteoglycans, and glycopro-
teins. And as mentioned, some of these cells secrete erythropoietin. The kidneys
also have a lymphatic drainage system, the function of which is to remove soluble
proteins from the interstitium that are too large to penetrate the endothelium of
tissue capillaries.
The cortex and medulla differ from each other both structurally and function-
ally. In the cortex the tubules and blood vessels are intertwined randomly, some-
thing like a plateful of spaghetti, whereas in the medulla they are organized in
6 / CHAPTER 1

Cortex

Medulla

Papilla
Renal vein
Renal artery
Calyx

Pelvis
Ureter

Capsule

Figure 1–2. Major structural components of the kidney. (Reproduced with permission
from Kibble J, Halsey CR. The Big Picture: Medical Physiology. New York: McGraw-Hill; 2009.)

parallel arrays like bundles of pencils. In both cases tubules and blood vessels are
very close to each other (notice the tight packing of medullary elements shown in
Figure 1–3). In addition, the cortex, but not the medulla, contains scattered spheri-
cal structures called renal corpuscles. The arrangements of tubules, blood vessels,
and renal corpuscles are crucial for renal function, as will be developed later.
In the medulla each pyramid is
divisible into an outer zone and an
The cortex contains renal inner zone. The outer zone borders
the cortex, and the inner zone contin-
corpuscles, coiled blood vessels ues to the papilla. The outer zone is
and coiled tubules; the medulla further subdivided into an outer stripe
contains straight blood vessels and an inner stripe. All these distinc-
and straight tubules. tions reflect the organized arrange-
ment of tubules and blood vessels.

THE TUBULAR SYSTEM

Each kidney contains approximately 1 million nephrons, which are the
tubules that sequentially modify filtered fluid to form the final urine.
One nephron is shown diagrammatically in Figure 1–4. Each nephron
begins with a spherical filtering component, called the renal corpuscle, followed by
a long tubule leading out of the renal corpuscle that continues until it merges with
the tubules of other nephrons, like a series of tributaries that form a river. fte
merged tubules are collecting ducts, which are themselves long tubes. Collecting
ducts eventually merge with other collecting ducts in the renal papilla to form a
ureter that conveys urine to the bladder. Although nephrons and collecting ducts
 RENAL FUNCTIONS, BASIC PROCESSES, AND ANATOMY / 7

C
A
C
A T
T
CD
T
I

CD C
A

I
CD

Figure 1–3. Slice through the renal medulla illustrating the close proximity of the tubu-
lar and vascular elements. Thin descending limbs (T), thick ascending limbs (A), collecting
ducts (CD), and parallel vasa recta (C) are embedded in the interstitium (I), which contains
sparse interstitial cells. (Reproduced with permission from Mescher AL. Junqueira’s Basic
Histology: Text and Atlas. 12th ed. New York: McGraw-Hill; 2010.)

Afferent Macula
arteriole densa Distal tubule
Bowman’s
capsule
Proximal
tubule
Cortical
collecting
duct
Thick
ascending
limb
Thin
descending
limb
Medullary
Thin collecting
ascending duct
limb

Figure 1–4. Components of the nephron. (Reproduced with permission from Kibble J,
Halsey CR: The Big Picture, Medical Physiology. New York: McGraw-Hill, 2009.)
8 / CHAPTER 1

have different embryological origins, they form a continuous functional unit. For
example, the commonly used term “distal nephron” implies elements of both the
nephron the collecting duct.

The Renal Corpuscle

The renal corpuscle is a hollow sphere (Bowman’s capsule) composed of epithelial
cells. It is filled with blood vessels: a compact tuft of interconnected capillary
loops called the glomerulus (Figure 1–5A to D). Two closely spaced arterioles pen-
etrate Bowman’s capsule at a region called the vascular pole. The afferent arteri-
ole brings blood into the capillaries of the glomerulus, and the efferent arteriole
drains blood from it. Another cell type—the mesangial cell—is found in close
association with the capillary loops of the glomerulus. Glomerular mesangial cells

Flow of blood Parietal layer of

Flow of filtrate glomerular capsule
Capsular space Afferent arteriole
Vascular pole
Tubular pole Proximal
Proximal convoluted
convoluted Juxtaglomerular tubule
tubule apparatus: Capsular
Juxtaglomerular space
cell
Macula densa Glomerulus
Glomerulus
Distal tubule Afferent
arteriole
Podocyte of visceral
Macula
layer of glomerular Efferent arteriole densa
capsule
Endothelium Distal tubule
Pedicel of glomerulus

A Renal corpuscle B Histology of renal corpuscle

Pedicels Podocyte cell body

Podocyte
Capillary lumen
Filtration Pedicels
membrane:
Basement
membrane Glomerular
capillary
Fenestrated covered by
capillary podocytes with
endothelium pedicels

Filtration slits

C Glomerular capillaries & podocyte D

Figure 1–5. A, Anatomy of the renal corpuscle. B, Histology of renal corpuscle.

C, Drawing of podocyte and glomerular capillary. D, Scanning EM of podocyte covering
glomerular capillaries. (Reproduced with permission from McKinley M, O’Loughlin VD.
Human Anatomy. 2nd ed. New York: McGraw-Hill; 2008.)
 RENAL FUNCTIONS, BASIC PROCESSES, AND ANATOMY / 9

act as phagocytes and remove trapped material from the basement membrane of
the capillaries. They also contain large numbers of myofilaments and can contract
in response to a variety of stimuli in a manner similar to vascular smooth muscle
cells. The space within Bowman’s capsule that is not occupied by capillaries and
mesangial cells is called the urinary space or Bowman’s space, and it is into this
space that fluid filters from the glomerular capillaries before flowing into the first
portion of the tubule, located opposite the vascular pole.
The structure and properties of the filtration barrier that separates plasma in
the glomerular capillaries from fluid in urinary space are crucial for renal function
and will be described thoroughly in the next chapter. For now, we note simply that
the functional significance of the filtration barrier is that it permits the filtration
of large volumes of fluid from the capillaries into Bowman’s space, but restricts
filtration of large plasma proteins such as albumin.

The Tubule
fte tubule begins at and leads out of Bowman’s capsule on the side opposite
the vascular pole. fte tubule has a number of segments divided into subdivi-
sions (Figure 1–6). To avoid excessive detail we usually group together 2 or
more contiguous tubular segments
when discussing function. Table 1–1
“The renal tubules operate like lists the names and sequence of the
various tubular segments. ftroughout
assembly lines; they accept
its length the tubule is made up of a
the fluid coming into them, single layer of epithelial cells resting
perform some segment-specific on a basement membrane and con-
modification of the fluid, and nected by tight junctions that physi-
send it on to the next segment.” cally link the cells together (like the
plastic form that holds a 6 pack of soft
drinks together).
The proximal tubule is the first segment. It drains Bowman’s capsule and con-
sists of a coiled segment—the proximal convoluted tubule—followed by a shorter
straight segment—the proximal straight tubule (sometimes called the S3 seg-
ment). The coiled segment is entirely within the cortex, whereas the straight seg-
ment descends a short way into the outer medulla (labeled 3 in Figure 1–6). Most
of the length and functions of the proximal tubule are in the cortex.
The next segment is the descending thin limb of the loop of Henle (or sim-
ply the descending thin limb). The descending thin limbs of all nephrons begin
at the same level, at the point where they connect to straight portions of proximal
tubules in the outer medulla. This marks the border between the outer and inner
stripes of the outer medulla. In contrast, the descending thin limbs of different
nephrons penetrate down to varying depths in the medulla. At their ending they
abruptly reverse at a hairpin turn and become an ascending portion of the loop
of Henle parallel to the descending portion. In long loops, the ones that have
penetrated deep into the inner medulla, the epithelium of the first portion of
the ascending limb remains thin, although different functionally from that of
10 / CHAPTER 1

9 8

9*
7 1
Cortex 2

1
7 10
2
3

6
Outer 3
stripe
Outer medulla

Inner 11 4
stripe

4
12
Inner
medula 5

Figure 1–6. Standard nomenclature for structures of the kidney (1988 Commission of the
International Union of Physiological Sciences). Shown are a short-looped (right side) and a
long-looped, or juxtamedullary nephron (left side), together with the collecting system (not
drawn to scale). A cortical medullary ray—the part of the cortex that contains the straight
proximal tubules, cortical thick ascending limbs, and cortical collecting ducts—is delineated
by a dashed line. 1, renal corpuscle (Bowman’s capsule and the glomerulus; 2, proximal
convoluted tubule; 3, proximal straight tubule; 4, descending thin limb; 5, ascending thin
limb; 6, thick ascending limb; 7, macula densa (located within the final portion of the thick
ascending limb); 8, distal convoluted tubule; 9, connecting tubule; 9*, connecting tubule
of a juxtamedullary nephron that arches upward to form a so-called arcade (there are only
a few of these in the human kidney); 10, cortical collecting duct; 11, outer medullary col-
lecting duct; 12, inner medullary collecting duct. (Reproduced with permission from Kriz W,
Bankir L. A standard nomenclature for structures of the kidney. The Renal Commission of the
International Union of Physiological Sciences (IUPS). Am J Physiol. 1988; 254:F1–F8.)
 RENAL FUNCTIONS, BASIC PROCESSES, AND ANATOMY / 11

Table 1–1. Terminology for tubular segments

Segments Terms used in text

Proximal convoluted tubule Proximal tubule
Proximal straight tubule
Descending thin limb of the loop of Henle Loop of Henle
Ascending thin limb of the loop of Henle
Thick ascending limb of the loop of Henle
Distal convoluted tubule Distal tubule
Distal tubule Distal nephron
Connecting tubule
Cortical collecting duct
Outer medullary collecting duct Medullary collecting duct
Inner medullary collecting duct

the descending limb. This segment is called the ascending thin limb of Henle’s
loop, or simply the ascending thin limb (labeled 5 Figure 1–6). Further up the
ascending portion the epithelium thickens, and this next segment is called the
thick ascending limb of Henle’s loop, or simply the thick ascending limb. In short
loops (depicted in the right side of Figure 1–6), there is no ascending thin portion,
and the thick ascending portion begins right at the hairpin loop. All thick ascend-
ing limbs begin at the same level, which marks the border between the inner and
outer medulla. Therefore, the thick ascending limbs begin at a slightly deeper level
in the medulla than do thin descending limbs. Each thick ascending limb rises
back into the cortex right back to the very same Bowman’s capsule from which the
tubule originated. Here it passes directly between the afferent and efferent arte-
rioles at the vascular pole of Bowman’s capsule. The cells in the thick ascending
limb closest to Bowman’s capsule (between the afferent and efferent arterioles) are
specialized cells known as the macula densa (labeled 7 in Figure 1–6). The macula
densa marks the end of the thick ascending limb and the beginning of the distal
convoluted tubule (labeled 8 in Figure 1–6). This is followed by the connecting
tubule, which leads to the cortical collecting duct, the first portion of which is
called the initial collecting tubule.
Connecting tubules from several nephrons merge to form a given cortical col-
lecting duct (Figure 1–6). All the cortical collecting ducts then run downward to
enter the medulla and become outer medullary collecting ducts, and continue to
become inner medullary collecting ducts. These merge to form larger ducts, the
last portions of which are called papillary collecting ducts, each of which empties
into a calyx of the renal pelvis. Each renal calyx is continuous with the ureter. The
tubular fluid, now properly called urine, is not altered after it enters a calyx.
Up to the distal convoluted tubule, the epithelial cells forming the wall of a
nephron in any given segment are homogeneous and distinct for that segment.
For example, the thick ascending limb contains only thick ascending limb cells.
12 / CHAPTER 1

However, beginning in the second half of the distal convoluted tubule the epi-
thelium contains 2 intermingled cell types. The first constitutes the majority of
cells in a particular segment and are
usually called principal cells. Thus,
Loops of Henle penetrate there are segment-specific principal
cells in the distal convoluted tubule,
to various depths, then
connecting tubule, and collecting
turn upward back to the ducts. Interspersed among the seg-
Bowman’s capsules where the ment-specific cells in these regions
tubules began. are cells of a second type, called
intercalated cells, that is, they are
intercalated between the principal
cells. The last portion of the medullary collecting duct contains neither principal
cells nor intercalated cells but is composed entirely of a distinct cell type called the
inner medullary collecting-duct cells.

The Juxtaglomerular Apparatus

Earlier we mentioned the macula densa, a portion of the end of the thick ascend-
ing limb at the point where this segment comes between the afferent and efferent
arterioles at the vascular pole of the renal corpuscle from which the tubule arose.
This entire area is known as the juxtaglomerular (JG) apparatus, which, as will be
described in Chapter 7, plays a very important signaling function. (Do not con-
fuse the term JG apparatus with juxtamedullary nephron, meaning a nephron with
a glomerulus located close to the cortical-medullary border.) Each JG apparatus is
made up of 3 cell types: (1) granular cells, which are differentiated smooth muscle
cells in the walls of the afferent arterioles; (2) extraglomerular mesangial cells; and
(3) macula densa cells, which are specialized thick ascending limb epithelial cells
(see Figure 7–4).
The granular cells are named because they contain secretory vesicles that
appear granular in light micrographs. These granules contain the hormone
renin (pronounced REE’-nin). As we will describe in Chapter 7, renin is a cru-
cial substance for control of renal function and systemic blood pressure. The
extraglomerular mesangial cells are morphologically similar to and continuous
with the glomerular mesangial cells, but lie outside Bowman’s capsule. The
macula densa cells are detectors of the flow rate and composition of the fluid
within the nephron at the very end of the thick ascending limb. These detector
cells contribute to the control of glomerular filtration rate (GFR—see below)
and to the control of renin secretion.

BASIC RENAL EXCRETORY PROCESSES

fte working structures of the kidney are the nephrons and collecting
tubules into which the nephrons drain. Figure 1–7 illustrates the mean-
ing of several key words that we use to describe how the kidneys function.
It is essential that any student of the kidney grasp their meaning.
 RENAL FUNCTIONS, BASIC PROCESSES, AND ANATOMY / 13

Artery Afferent Glomerular

arteriole capillary

Efferent
arteriole

Bowman’s
2
capsule
1. Glomerular filtration
2. Tubular secretion
3. Tubular reabsorption
Tubule

3 Peritubular capillary

Vein

Urinary
excretion

Figure 1–7. Fundamental elements of renal function—glomerular filtration, tubular

secretion and tubular reabsorption—and the association between the tubule and vas-
culature in the cortex.

Filtration is the process by which water and solutes in the blood leave the vas-
cular system through the filtration barrier and enter Bowman’s space (a space that
is topologically outside the body). Secretion is the process of transporting sub-
stances into the tubular lumen from the cytosol of epithelial cells that form the
walls of the nephron. Secreted substances may originate by synthesis within the
epithelial cells or, more often, by crossing the epithelial layer from the surround-
ing renal interstitium. Reabsorption is the process of moving substances from
the lumen across the epithelial layer into the surrounding interstitium.1 In most
cases, reabsorbed substances then move into surrounding blood vessels, so that
the term reabsorption implies a 2-step process of removal from the tubular lumen
followed by movement into the blood. Excretion means exit of the substance from
the body (ie, the substance is present in the final urine produced by the kidneys).
Synthesis means that a substance is constructed from molecular precursors, and

1
We use the term “reabsorption” to describe the movement of filtered substances back into the blood
because they are reentering the blood. “Absorption” describes the original entrance of consumed
substances from the gastrointestinal tract into the blood.
14 / CHAPTER 1

catabolism means the substance is broken down into smaller component mol-
ecules. The renal handling of any substance consists of some combination of
these processes.

Glomerular Filtration
Urine formation begins with glomerular filtration, the bulk flow of fluid from
the glomerular capillaries into Bowman’s capsule. The glomerular filtrate (ie, the
fluid within Bowman’s capsule) is very much like blood plasma, but contains very
little total protein because the large plasma proteins like albumin and the globu-
lins are virtually excluded from moving through the filtration barrier. Smaller
proteins, such as many of the peptide hormones, are present in the filtrate, but
their mass in total is miniscule compared with the mass of large plasma proteins
in the blood. The filtrate contains most inorganic ions and low-molecular-weight
organic solutes in virtually the same concentrations as in the plasma. Substances
that are present in the filtrate at the same concentration as found in the plasma
are said to be freely filtered. (Note that freely filtered does not mean all filtered.
It just means that the amount filtered is in exact proportion to the fraction of
plasma volume that is filtered.) Many low-molecular-weight components of blood
are freely filtered. Among the most common substances included in the freely
filtered category are the ions sodium, potassium, chloride, and bicarbonate; the
uncharged organics glucose and urea; amino acids; and peptides such as insulin
and antidiuretic hormone.
The volume of filtrate formed per unit time is known as the GFR. In a healthy
young adult male, the GFR is an incredible 180 L/day (125 mL/min)! Contrast
this value with the net filtration of fluid across all the other capillaries in the
body: approximately 4 L/day. The implications of this huge GFR are extremely
important. When we recall that the average total volume of plasma in humans is
approximately 3 L, it follows that the entire plasma volume is filtered by the kid-
neys some 60 times a day. The opportunity to filter such huge volumes of plasma
enables the kidneys to excrete large quantities of waste products and to regulate
the constituents of the internal environment very precisely. One of the general
consequences of healthy aging as well as many kidney diseases is a reduction in
the GFR (see Chapter 3).

Tubular Reabsorption and Tubular Secretion

The volume and composition of the final urine are quite different from those of
the glomerular filtrate. Clearly, almost all the filtered volume must be reabsorbed;
otherwise, with a filtration rate of 180 L/day, we would urinate ourselves into
dehydration very quickly. As the filtrate flows from Bowman’s capsule through
the various portions of the tubule, its composition is altered, mostly by removing
material (tubular reabsorption) but also by adding material (tubular secretion). As
described earlier, the tubule is, at all points, intimately associated with the vascu-
lature, a relationship that permits rapid transfer of materials between the capillary
plasma and the lumen of the tubule via the interstitial space.
 RENAL FUNCTIONS, BASIC PROCESSES, AND ANATOMY / 15

Table 1–2. Average values for several substances handled by filtration

and reabsorption

Substance Amount filtered per day Amount excreted % Reabsorbed

Water, L 180 1.8 99.0
Sodium, g 630 3.2 99.5
Glucose, g 180 0 100
Urea, g 56 28 50

Most of the tubular transport consists of reabsorption rather than tubular

secretion. An idea of the magnitude and importance of tubular reabsorption can
be gained from Table 1–2, which summarizes data for a few plasma components
that undergo reabsorption. The values in Table 1–2 are typical for a healthy young
adult on an average diet. There are at least 3 important generalizations to be
drawn from this table:
1. Because of the huge GFR, the quantities filtered per day are enormous, gen-
erally larger than the amounts of the substances in the body. For example,
the body of a 70-kg person contains about 42 L of water, but the volume of
water filtered each day may be as large as 180 L.
2. Reabsorption of waste products, such as urea, is partial, so that large frac-
tions of their filtered amounts are excreted in the urine.
3. Reabsorption of most “useful” plasma components (eg, water, electrolytes,
and glucose) is either complete (eg, glucose), or nearly so (eg, water and
most electrolytes), so that very little of the filtered amounts are excreted in
the urine.
For each plasma substance, a particular combination of filtration, reabsorp-
tion, and secretion applies. The relative proportions of these processes then deter-
mine the amount excreted. A critical point is that the rates of these processes are
subject to physiological control. By triggering changes in the rates of filtration,
reabsorption, or secretion when the body content of a substance goes above or
below normal, these mechanisms regulate excretion to keep the body in balance.
For example, consider what happens when a person drinks a large quantity of
water: Within 1 to 2 hours, all the excess water has been excreted in the urine,
partly as the result of an increase in GFR but mainly as the result of decreased
tubular reabsorption of water. The body is kept in balance for water by increas-
ing excretion.

Metabolism by the Tubules

Although most sources list glomerular filtration, tubular reabsorption, and tubu-
lar secretion as the 3 basic renal processes, we cannot overlook metabolism by
16 / CHAPTER 1

the tubular cells. The tubular cells extract organic nutrients from the glomerular
filtrate or peritubular capillaries and metabolize them as dictated by the cells’ own
nutrient requirements. In so doing, the renal cells are behaving no differently than
any other cells in the body. In addition, there are other metabolic transformations
performed by the kidney that are directed toward altering the composition of
the urine and plasma. The most important of these are gluconeogenesis, and the
synthesis of ammonium from glutamine and the production of bicarbonate, both
described in Chapter 9.

Regulation of Renal Function

The most complex and least understood feature of the kidneys is regulation of
renal processes. Details, to the extent known, will be presented in later chapters.
Neural signals, hormonal signals, and intrarenal chemical messengers combine
to regulate the processes described above in a manner to help the kidneys meet
the needs of the body. Neural signals originate in the sympathetic celiac plexus.
These sympathetic neural signals exert major control over renal blood flow,
glomerular filtration and the release of vasoactive substances that affect both
the kidneys and the peripheral vasculature. Known hormonal signals origi-
nate in the adrenal gland, pituitary gland, parathyroid glands, and heart. The
adrenal cortex secretes the steroid hormones aldosterone and cortisol, and the
adrenal medulla secretes the catecholamines epinephrine and norepinephrine.
All of these hormones, but mainly aldosterone, are regulators of sodium and
potassium excretion by the kidneys. The posterior pituitary gland secretes the
hormone arginine vasopressin (AVP, also called ADH). ADH is a major regula-
tor of water and urea excretion, as well as a partial regulator of sodium excre-
tion. The heart secretes hormones—natriuretic peptides—that increase sodium
excretion by the kidneys. Another complicated aspect of regulation lies in the
realm of intrarenal chemical messengers (ie, messengers that originate in one
part of the kidney and act in another part). It is clear that an array of substances
(eg, nitric oxide, purinergic agonists, superoxide, and eicosanoids) influence
basic renal processes. The precise roles of these substances are just now being
elucidated.
Two points about regulation should be kept in mind. First, excretion of major
substances is regulated by overlapping, redundant controls. Failure of one may
be compensated by the operation of another. Second, control systems adapt to
chronic conditions and may change in effectiveness over time.
In ensuing chapters of this book we discuss specific mechanisms of reabsorp-
tion and secretion. When describing regulation of these mechanisms we are also
implying regulation of excretion because any substance present in the tubule and
not reabsorbed is destined to be excreted.

Overview of Regional Function

We conclude this chapter with a broad overview of the tasks performed by the
individual nephron segments. Later, we examine renal function substance by
 RENAL FUNCTIONS, BASIC PROCESSES, AND ANATOMY / 17

substance and see how tasks performed in the various regions combine to produce
an overall result that is useful for the body.
The glomerulus is the site of filtration—about 180 L/day of volume and
proportional amounts of solutes that are freely filtered, which is the case for
most solutes (large plasma proteins are an exception). The glomerulus is where
the greatest mass of excreted substances enters the nephron. The proximal tubule
(convoluted and straight portions together) reabsorbs about two thirds of the fil-
tered water, sodium, and chloride. It reabsorbs all of the useful organic molecules
that the body conserves (eg, glucose, amino acids). It reabsorbs significant frac-
tions, but by no means all, of many important ions, such as potassium, phos-
phate, calcium, and bicarbonate. It is the site of secretion of a number of organic
substances that are either metabolic waste products (eg, uric acid, creatinine) or
drugs (eg, penicillin) that clinicians must administer appropriately to make up
for renal excretion.
The loop of Henle contains different segments that perform different func-
tions, but the key functions occur in the thick ascending limb. As a whole, the
loop of Henle reabsorbs about 20% of the filtered sodium and chloride and 10%
of the filtered water. A crucial consequence of these different proportions is that,
by reabsorbing relatively more salt than water, the luminal fluid becomes diluted
relative to normal plasma and the surrounding interstitium. During periods when
the kidneys excrete dilute final urine, the role of the loop of Henle in diluting the
luminal fluid is crucial.
The end of the loop of Henle contains cells of the macula densa, which sense
the sodium and chloride content of the lumen and generate signals that influ-
ence other aspects of renal function, specifically the renin-angiotensin system
(discussed in Chapter 7). The distal tubule and connecting tubule together

Table 1–3. Normal plasma concentrations of key solutes handled by the kidneys
Sodium 140  5 mEq/L
Potassium 4.1  0.8 mEq/L
Calcium (free fraction) 1.0  0.1 mmol/L
Magnesium 0.9  0.1 mmol/L
Chloride 105  6 mEq/L
Bicarbonate 25  5 mEq/L
Phosphate 1.1  0.1 mmol/L
Glucose 5  1 mmol/L
Urea 5  1 mmol/L
Creatinine 1  0.2 mg/dL
Protein (total) 7  1 g/L
18 / CHAPTER 1

reabsorb some additional salt and water, perhaps 5% of each. The cortical col-
lecting duct is where several connecting tubules join to form a single tubule.
Cells of the connecting tubule and cortical collecting duct are strongly respon-
sive to and are regulated by the hormones angiotensin II and aldosterone, which
enhance sodium reabsorption. ADH enhances water reabsorption in the collect-
ing ducts. The degree to which these processes are stimulated or not stimulated
plays a major role in regulating the amount of solutes and water present in the
final urine.
The medullary collecting duct continues the functions of the cortical col-
lecting duct in salt and water reabsorption. In addition, it plays a major role in
the excretion of acids and bases, and the inner medullary collecting is impor-
tant in regulating urea excretion. The final result of these various transport
processes to keep the various plasma solutes close to the typical values is shown
in Table 1–3.

KEY CONCEPTS
In addition to excreting waste, the kidneys perform many necessary functions in
partnership with other body organ systems.

The kidneys regulate the excretion of many substances at a rate that balances their
input, thereby maintaining appropriate body content of those substances.

A major function of the kidneys is to regulate the volume and osmolality of extra-
cellular fluid volume.

The kidneys are composed mainly of tubules and closely associated blood vessels.

Each functional renal unit is composed of a filtering component (glomerulus) and

a transporting tubular component (the nephron and collecting duct).

The tubules are made up of multiple segments with distinct functions.

Basic renal mechanisms consist of filtering a large volume, reabsorbing most of it,
and adding substances by secretion, and, in some cases, synthesis.
 RENAL FUNCTIONS, BASIC PROCESSES, AND ANATOMY / 19

STUDY QUESTIONS

1–1. Renal corpuscles are located

a. along the corticomedullary border.
b. throughout the cortex.
c. throughout the cortex and outer medulla.
d. throughout the whole kidney.
1–2. Relative to the number of glomeruli, how many loops of Henle, and how many
collecting ducts are there?
a. Same number of loops of Henle; same number of collecting ducts.
b. Fewer loops of Henle; fewer collecting ducts.
c. Same number of loops of Henle; fewer collecting ducts.
d. Same number of loops of Henle; more collecting ducts.
1–3. It is possible for the body to be in balance for a substance when
a. the amount of the substance in the body is constant.
b. the amount of the substance in the body is higher than normal.
c. the input of the substance into the body is higher than normal.
d. in all of these situations.
1–4. The macula densa is a group of cells located in the wall of
a. Bowman’s capsule.
b. the afferent arteriole.
c. the end of the thick ascending limb.
d. the descending thin limb.
1–5. The volume of fluid entering the tubules by glomerular filtration in 1 day is typically
a. about 3 times the renal volume.
b. about the same as the volume filtered by all the capillaries in the rest
of the body.
c. about equal to the circulating plasma volume.
d. more than the total volume of water in the body.
1–6. In the context of the kidney, secretion of a substance implies that
a. it is transported from tubular cells into the tubular lumen.
b. it is filtered into Bowman’s capsule.
c. it is present in the final urine that is excreted.
d. it is synthesized by the tubular cells.