24.

11 LIVER AND GALLBLADDER 909

form called trypsinogen (trip-SIN-oˉ-jen). Pancreatic acinar narrow extensions of the parietal peritoneum that suspend the
cells also secrete a protein called trypsin inhibitor that com- liver from the diaphragm.
bines with any trypsin formed accidentally in the pancreas or in The parts of the gallbladder include the broad fundus, which
pancreatic juice and blocks its enzymatic activity. When tryp- projects inferiorly beyond the inferior border of the liver; the
sinogen reaches the lumen of the small intestine, it encounters body, the central portion; and the neck, the tapered portion. The
an activating brush-border enzyme called enterokinase (en⬘- body and neck project superiorly.
ter-oˉ-KĪ -naˉs), which splits off part of the trypsinogen molecule
to form trypsin. In turn, trypsin acts on the inactive precursors
(called chymotrypsinogen, procarboxypeptidase, and pro- Histology of the Liver and Gallbladder
elastase) to produce chymotrypsin, carboxypeptidase, and elas- Histologically, the liver is composed of several components
tase, respectively. (Figure 24.16a–c):
CHECKPOINT 1. Hepatocytes. Hepatocytes (hepat- ⫽ liver; -cytes ⫽ cells)
24. Describe the duct system connecting the pancreas to the are the major functional cells of the liver and perform a wide
duodenum. array of metabolic, secretory, and endocrine functions. These
25. What are pancreatic acini? How do their functions differ are specialized epithelial cells with 5 to 12 sides that make up
from those of the pancreatic islets (islets of Langerhans)?
about 80% of the volume of the liver. Hepatocytes form com-
26. What are the digestive functions of the components of
plex three-dimensional arrangements called hepatic laminae
pancreatic juice?
(LAM-i-nē). The hepatic laminae are plates of hepatocytes
one cell thick bordered on either side by the endothelial-lined
vascular spaces called hepatic sinusoids. The hepatic laminae
24.11 Liver and Gallbladder are highly branched, irregular structures. Grooves in the cell
membranes between neighboring hepatocytes provide spaces
OBJECTIVE for canaliculi (described next) into which the hepatocytes
• Describe the location, anatomy, histology, and functions secrete bile. Bile, a yellow, brownish, or olive-green liquid
of the liver and gallbladder.
secreted by hepatocytes, serves as both an excretory product
The liver is the heaviest gland of the body, weighing about 1.4 kg and a digestive secretion.
(about 3 lb) in an average adult. Of all of the organs of the body, 2. Bile canaliculi. Bile canaliculi (kan-a-LIK-uˉ-li ⫽ small ca-
it is second only to the skin in size. The liver is inferior to the nals) are small ducts between hepatocytes that collect bile
diaphragm and occupies most of the right hypochondriac and produced by the hepatocytes. From bile canaliculi, bile passes
part of the epigastric regions of the abdominopelvic cavity (see into bile ductules and then bile ducts. The bile ducts merge
Figure 1.12b). and eventually form the larger right and left hepatic ducts,
The gallbladder (gall- ⫽ bile) is a pear-shaped sac that is which unite and exit the liver as the common hepatic duct
located in a depression of the posterior surface of the liver. It is (see Figure 24.15). The common hepatic duct joins the cystic
7–10 cm (3–4 in.) long and typically hangs from the anterior infe- duct (cystic ⫽ bladder) from the gallbladder to form the com-

24
rior margin of the liver (Figure 24.15a). mon bile duct. From here, bile enters the duodenum of the
small intestine to participate in digestion.

C H A P T E R
Anatomy of the Liver and Gallbladder 3. Hepatic sinusoids. Hepatic sinusoids are highly permeable
blood capillaries between rows of hepatocytes that receive
The liver is almost completely covered by visceral peritoneum
oxygenated blood from branches of the hepatic artery and
and is completely covered by a dense irregular connective tissue
nutrient-rich deoxygenated blood from branches of the hepatic
layer that lies deep to the peritoneum. The liver is divided into two
portal vein. Recall that the hepatic portal vein brings venous
principal lobes—a large right lobe and a smaller left lobe—by
blood from the gastrointestinal organs and spleen into the
the falciform ligament, a fold of the mesentery (Figure 24.15a).
liver. Hepatic sinusoids converge and deliver blood into a cen-
Although the right lobe is considered by many anatomists to in-
tral vein. From central veins the blood flows into the hepatic
clude an inferior quadrate lobe (kwa-DRAˉT) and a posterior
veins, which drain into the inferior vena cava (see Figure 21.28).
caudate lobe (KAW-daˉt), based on internal morphology (primar-
In contrast to blood, which flows toward a central vein, bile
ily the distribution of blood vessels), the quadrate and caudate
flows in the opposite direction. Also present in the hepatic sinu-
lobes more appropriately belong to the left lobe. The falciform
soids are fixed phagocytes called stellate reticuloendothelial
ligament extends from the undersurface of the diaphragm be-
cells (STEL-aˉt re-tik⬘-uˉ-loˉ-en⬘-doˉ-THĒ-lē-al) or hepatic mac-
tween the two principal lobes of the liver to the superior surface
rophages, which destroy worn-out white and red blood cells,
of the liver, helping to suspend the liver in the abdominal cavity.
bacteria, and other foreign matter in the venous blood draining
In the free border of the falciform ligament is the ligamentum
from the gastrointestinal tract.
teres (round ligament), a remnant of the umbilical vein of the
fetus (see Figure 21.30a, b); this fibrous cord extends from the Together, a bile duct, branch of the hepatic artery, and branch
liver to the umbilicus. The right and left coronary ligaments are of the hepatic vein are referred to as a portal triad (tri- ⫽ three).
910 CHAPTER 24 • THE DIGESTIVE SYSTEM

Figure 24.16 Histology of the liver.

Liver
Histologically, the liver is composed of hepatocytes, bile canaliculi,
and hepatic sinusoids.
Inferior vena cava
Hepatic artery
Hepatic portal vein
Bile canaliculi
Hepatic
Central To hepatic sinusoid
Connective Hepatocyte vein vein Portal triad:
tissue Hepatic Bile duct
laminae
Branch of
Portal triad: hepatic portal
Bile duct vein
Branch Branch of
of hepatic hepatic artery
artery
Hepatic
Branch laminae
of hepatic Hepatocyte
portal vein
Stellate
reticuloendothelial
Central vein (Kupffer) cell

Connective
tissue
Hepatic
sinusoids

(a) Overview of histological components of liver (b) Details of histological components of liver

Hepatocyte

Central vein

Hepatic sinusoid

LM 100x

LM 50x
Portal triad:
Branch of hepatic artery

Bile duct

Branch of hepatic portal vein

LM 150x
(c) Photomicrographs
 24.11 LIVER AND GALLBLADDER 911
Portal triad
Central
vein

Portal
triad

Central Central
vein vein

Hepatic lobule Portal lobule

Zone 3

Zone 2

Zone 1

(e) Details of hepatic acinus

Hepatic acinus

(d) Comparison of three units of liver structure and function Which type of cell in the liver is phagocytic?

The hepatocytes, bile duct system, and hepatic sinusoids can closest to the branches of the portal triad and the first to re-
be organized into anatomical and functional units in three differ- ceive incoming oxygen, nutrients, and toxins from incoming
ent ways: blood. These cells are the first ones to take up glucose and
store it as glycogen after a meal and break down glycogen to
1. Hepatic lobule. For years, anatomists described the hepatic
glucose during fasting. They are also the first to show morpho-
lobule as the functional unit of the liver. According to this
logical changes following bile duct obstruction or exposure to
model, each hepatic lobule is shaped like a hexagon (six-sided
toxic substances. Zone 1 cells are the last ones to die if circula-
structure) (Figure 24.16d, left). At its center is the central vein,
tion is impaired and the first ones to regenerate. Cells in zone
and radiating out from it are rows of hepatocytes and hepatic
3 are farthest from branches of the portal triad and are the last
sinusoids. Located at three corners of the hexagon is a portal
to show the effects of bile obstruction or exposure to toxins,
triad. This model is based on a description of the liver of adult
the first ones to show the effects of impaired circulation, and
pigs. In the human liver it is difficult to find such well-defined
the last ones to regenerate. Zone 3 cells also are the first to

24
hepatic lobules surrounded by thick layers of connective tissue.
show evidence of fat accumulation. Cells in zone 2 have struc-
2. Portal lobule. This model emphasizes the exocrine function tural and functional characteristics intermediate between the

C H A P T E R
of the liver, that is, bile secretion. Accordingly, the bile duct of cells in zones 1 and 3.
a portal triad is taken as the center of the portal lobule. The
portal lobule is triangular in shape and is defined by three The hepatic acinus is the smallest structural and functional unit
imaginary straight lines that connect three central veins that of the liver. Its popularity and appeal are based on the fact that it
are closest to the portal triad (Figure 24.16d, right). This provides a logical description and interpretation of (1) patterns of
model has not gained widespread acceptance. glycogen storage and release and (2) toxic effects, degeneration,
3. Hepatic acinus. In recent years, the preferred structural and and regeneration relative to the proximity of the acinar zones to
functional unit of the liver is the hepatic acinus (AS-i-nus). branches of the portal triad.
Each hepatic acinus is an approximately oval mass that in- The mucosa of the gallbladder consists of simple columnar
cludes portions of two neighboring hepatic lobules. The short epithelium arranged in rugae resembling those of the stomach.
axis of the hepatic acinus is defined by branches of the portal The wall of the gallbladder lacks a submucosa. The middle, mus-
triad—branches of the hepatic artery, vein, and bile ducts— cular coat of the wall consists of smooth muscle fibers. Contrac-
that run along the border of the hepatic lobules. The long axis tion of the smooth muscle fibers ejects the contents of the gall-
of the acinus is defined by two imaginary curved lines, which bladder into the cystic duct. The gallbladder’s outer coat is the
connect the two central veins closest to the short axis (Figure visceral peritoneum. The functions of the gallbladder are to store
24.16d, bottom). Hepatocytes in the hepatic acinus are ar- and concentrate the bile produced by the liver (up to tenfold)
ranged in three zones around the short axis, with no sharp until it is needed in the small intestine. In the concentration pro-
boundaries between them (Figure 24.16e). Cells in zone 1 are cess, water and ions are absorbed by the gallbladder mucosa.
912 CHAPTER 24 • THE DIGESTIVE SYSTEM

and toxins from the gastrointestinal tract (see Figure 21.28).

CLINICAL CONNECTION | Jaundice Branches of both the hepatic artery and the hepatic portal vein
Jaundice (JAWN-dis ⫽ yellowed) is a yellowish coloration of
carry blood into hepatic sinusoids, where oxygen, most of the
the sclerae (whites of the eyes), skin, and mucous membranes nutrients, and certain toxic substances are taken up by the he-
due to a buildup of a yellow compound called bilirubin. After patocytes. Products manufactured by the hepatocytes and nu-
bilirubin is formed from the breakdown of the heme pigment in aged trients needed by other cells are secreted back into the blood,
red blood cells, it is transported to the liver, where it is processed and which then drains into the central vein and eventually passes
eventually excreted into bile. The three main categories of jaundice into a hepatic vein. Because blood from the gastrointestinal
are (1) prehepatic jaundice, due to excess production of bilirubin; tract passes through the liver as part of the hepatic portal cir-
(2)  hepatic jaundice, due to congenital liver disease, cirrhosis of the culation, the liver is often a site for metastasis of cancer that
liver, or hepatitis; and (3) extrahepatic jaundice, due to blockage of originates in the GI tract.
bile drainage by gallstones or cancer of the bowel or the pancreas.
Because the liver of a newborn functions poorly for the first week
or so, many babies experience a mild form of jaundice called neona-
tal (physiological) jaundice that disappears as the liver matures. CLINICAL CONNECTION | Liver Function Tests
Usually, it is treated by exposing the infant to blue light, which con-
verts bilirubin into substances the kidneys can excrete. • Liver function tests are blood tests designed to determine
the presence of certain chemicals released by liver cells.
These include albumin globulinase, alanine aminotransfer-
ase (ALT), aspartate aminotransferase (AST), alkaline phosphatase
Blood Supply of the Liver
(ALP), gamma-glutamyl-transpeptidase (GGT), and bilirubin. The
The liver receives blood from two sources (Figure 24.17). tests are used to evaluate and monitor liver disease or damage.
From the hepatic artery it obtains oxygenated blood, and from Common causes of elevated liver enzymes include nonsteroidal
the hepatic portal vein it receives deoxygenated blood contain- anti-inflammatory drugs, cholesterol-lowering medications, some
ing newly absorbed nutrients, drugs, and possibly microbes antibiotics, alcohol, diabetes, infections (viral hepatitis and mono-
nucleosis), gallstones, tumors of the liver, and excessive use of
herbal supplements such as kava, comfrey, pennyroyal, dandelion
Figure 24.17 Hepatic blood flow: sources, path through the root, skullcap, and ephedra. •
liver, and return to the heart.

The liver receives oxygenated blood via the hepatic Functions of the Liver and Gallbladder
artery and nutrient-rich deoxygenated blood via the
hepatic portal vein. Each day, hepatocytes secrete 800–1000 mL (about 1 qt) of bile,
a yellow, brownish, or olive-green liquid. It has a pH of 7.6–8.6
OXYGENATED BLOOD FROM
NUTRIENT-RICH, and consists mostly of water, bile salts, cholesterol, a phospho-
1 DEOXYGENATED BLOOD
HEPATIC ARTERY FROM HEPATIC PORTAL VEIN
lipid called lecithin, bile pigments, and several ions.
The principal bile pigment is bilirubin (bil-i-ROO-bin). The
phagocytosis of aged red blood cells liberates iron, globin, and
bilirubin (derived from heme) (see Figure 19.5). The iron and
2 Hepatic sinusoids globin are recycled; the bilirubin is secreted into the bile and is
eventually broken down in the intestine. One of its breakdown
products—stercobilin (ster-koˉ-BĪ -lin)—gives feces their nor-
3 mal brown color.
Central vein
Bile is partially an excretory product and partially a digestive
secretion. Bile salts, which are sodium salts and potassium salts
of bile acids (mostly chenodeoxycholic acid and cholic acid),
4 Hepatic vein play a role in emulsification (e-mul⬘-si-fi-KAˉ-shun), the break-
down of large lipid globules into a suspension of small lipid glob-
ules. The small lipid globules present a very large surface area
that allows pancreatic lipase to more rapidly accomplish diges-
5 Inferior vena cava tion of triglycerides. Bile salts also aid in the absorption of lipids
following their digestion.
Although hepatocytes continually release bile, they increase
6 Right atrium of heart production and secretion when the portal blood contains more
bile acids; thus, as digestion and absorption continue in the
During the first few hours after a meal, how does small intestine, bile release increases. Between meals, after
the chemical composition of blood change as it flows most absorption has occurred, bile flows into the gallbladder for
through the liver sinusoids? storage because the sphincter of the hepatopancreatic ampulla
 24.12 SMALL INTESTINE 913
(sphincter of Oddi; see Figure 24.15) closes off the entrance to from the blood and secreted into bile. Most of the bilirubin in
the duodenum. The sphincter surrounds the hepatopancreatic bile is metabolized in the small intestine by bacteria and elimi-
ampulla. nated in feces.
• Synthesis of bile salts. Bile salts are used in the small intestine
for the emulsification and absorption of lipids.
CLINICAL CONNECTION | Gallstones
• Storage. In addition to glycogen, the liver is a prime storage
If bile contains either insufficient bile salts or lecithin or exces- site for certain vitamins (A, B12, D, E, and K) and minerals
sive cholesterol, the cholesterol may crystallize to form gall- (iron and copper), which are released from the liver when
stones. As they grow in size and number, gallstones may needed elsewhere in the body.
cause minimal, intermittent, or complete obstruction to the flow of
bile from the gallbladder into the duodenum. Treatment consists of
• Phagocytosis. The stellate reticuloendothelial (Kupffer) cells
using gallstone-dissolving drugs, lithotripsy (shock-wave therapy), or of the liver phagocytize aged red blood cells, white blood cells,
surgery. For people with a history of gallstones or for whom drugs or and some bacteria.
lithotripsy are not options, cholecystectomy (kō⬘-lē-sis-TEK-tō-mē)— • Activation of vitamin D. The skin, liver, and kidneys partici-
the removal of the gallbladder and its contents—is necessary. More pate in synthesizing the active form of vitamin D.
than half a million cholecystectomies are performed each year in the
United States. To prevent side effects resulting from a loss of the The liver functions related to metabolism are discussed more
gallbladder, patients should make lifestyle and dietary changes, in- fully in Chapter 25.
cluding the following: (1) limiting the intake of saturated fat;
(2)  avoiding the consumption of alcoholic beverages; (3) eating CHECKPOINT
smaller amounts of food during a meal and eating five to six smaller 27. Draw and label a diagram of the cell zones of a hepatic
meals per day instead of two to three larger meals; and (4) taking acinus.
vitamin and mineral supplements. • 28. Describe the pathways of blood flow into, through, and
out of the liver.
29. How are the liver and gallbladder connected to the
In addition to secreting bile, which is needed for absorption of duodenum?
dietary fats, the liver performs many other vital functions: 30. Once bile has been formed by the liver, how is it
collected and transported to the gallbladder for
• Carbohydrate metabolism. The liver is especially important in storage?
maintaining a normal blood glucose level. When blood glucose 31. Describe the major functions of the liver and
is low, the liver can break down glycogen to glucose and re- gallbladder.
lease the glucose into the bloodstream. The liver can also con-
vert certain amino acids and lactic acid to glucose, and it can
convert other sugars, such as fructose and galactose, into glu-
cose. When blood glucose is high, as occurs just after eating a 24.12 Small Intestine
meal, the liver converts glucose to glycogen and triglycerides
OBJECTIVES
for storage.

24
• Describe the location and structure of the small intestine.
• Lipid metabolism. Hepatocytes store some triglycerides; break • Identify the functions of the small intestine.

C H A P T E R
down fatty acids to generate ATP; synthesize lipoproteins,
which transport fatty acids, triglycerides, and cholesterol to Most digestion and absorption of nutrients occur in a long tube
and from body cells; synthesize cholesterol; and use choles- called the small intestine. Because of this, its structure is spe-
terol to make bile salts. cially adapted for these functions. Its length alone provides a
large surface area for digestion and absorption, and that area is
• Protein metabolism. Hepatocytes deaminate (remove the
further increased by circular folds, villi, and microvilli. The small
amino group, NH2, from) amino acids so that the amino acids
intestine begins at the pyloric sphincter of the stomach, coils
can be used for ATP production or converted to carbohydrates
through the central and inferior part of the abdominal cavity, and
or fats. The resulting toxic ammonia (NH3) is then converted
eventually opens into the large intestine. It averages 2.5 cm (1 in.)
into the much less toxic urea, which is excreted in urine. Hepa-
in diameter; its length is about 3 m (10 ft) in a living person and
tocytes also synthesize most plasma proteins, such as alpha
about 6.5 m (21 ft) in a cadaver due to the loss of smooth muscle
and beta globulins, albumin, prothrombin, and fibrinogen.
tone after death.
• Processing of drugs and hormones. The liver can detoxify
substances such as alcohol and excrete drugs such as penicil-
lin, erythromycin, and sulfonamides into bile. It can also Anatomy of the Small Intestine
chemically alter or excrete thyroid hormones and steroid hor- The small intestine is divided into three regions (Figure 24.18).
mones such as estrogens and aldosterone. The first part of the small intestine is the duodenum (doo⬘-oˉ-DĒ-
• Excretion of bilirubin. As previously noted, bilirubin, derived num or doo-OD-e-num), the shortest region, and is retroperito-
from the heme of aged red blood cells, is absorbed by the liver neal. It starts at the pyloric sphincter of the stomach and is in the