The Liver

M. Robert Dejong

Jeanine Rybyinski

OBJECTIVES

Identify the normal anatomy of the liver including the liver lobes, segments, fissures, ligaments, and hepatic vasculature.
Describe the different lobar divisions of the liver including anatomic, functional, and Couinaud’s segmental divisions.
List some of the various functions of the liver.
Discuss the laboratory values associated with liver function.
Explain the patient preparation, scanning technique, and sonographic appearance of the normal liver.
Discuss the pathophysiology and sonographic appearance of diffuse liver diseases including fatty infiltration, hepatitis, and cirrhosis.
Describe the differential diagnoses, clinical signs, symptoms and sonographic appearance of cystic and solid liver lesions.
Discuss ultrasound contrast enhancement of the liver, when to use it, and how it helps with diagnosing solid masses.
Discuss the benefits of elastography of the liver.

GLOSSARY

AFP (alpha-fetoprotein) a tumor marker frequently elevated in cases of hepatocellular carcinoma and certain testicular cancers

ALP (alkaline phosphatase) an enzyme found in liver tissue that can be elevated with biliary obstruction

ALT (alanine aminotransferase) a liver enzyme most specific to hepatocellular damage

AST (aspartate aminotransferase) an enzyme found in all tissues, but in largest amounts in the liver; an increase can indicate hepatocellular damage

falciform ligament fold in the parietal peritoneum that extends from the umbilicus to the diaphragm and contains the ligamentum teres

Glisson capsule a fibroelastic, connective tissue layer that surrounds the liver and the portal triads

hepatofugal blood flow away from the liver; normal flow in the hepatic veins is hepatofugal

hepatomegaly enlarged liver

hepatopetal blood flow toward the liver; normal flow in the portal vein is hepatopetal

jaundice yellowish pigmentation of the skin and whites of the eyes caused by increased levels of bilirubin in the blood

ligamentum teres remnant of the obliterated left umbilical vein seen as a triangular echogenic focus dividing the medial and lateral segments of the left lobe of the liver in the transverse plane

ligamentum venosum remnant of the ductus venosus seen as an echogenic line separating the caudate lobe from the left lobe

main lobar fissure divides the right and left lobes of the liver; seen in the sagittal plane as an echogenic line between the gallbladder neck and the main portal vein

porta hepatis known as the gateway to the liver, a fissure where the portal vein and hepatic artery enter the liver and the common hepatic duct exits

Riedel lobe anatomic variant in which the right lobe is enlarged and extends inferiorly as a tongue-like projection

The liver is an organ that is essential for life. It is the largest gland and solid organ in the body and is considered an accessory organ of digestion. It is important for the sonographer to understand the anatomy, physiology, and the various pathologies of the liver. The liver can be easily evaluated with ultrasound, and the use of new technologies—such as contrast and elastography—can help provide a lot of information about the liver for the physician. When a disease process of the liver is suspected, a sonography examination is commonly the first imaging test ordered because it can be quickly scheduled, has high patient acceptance, and does not use nephrotoxic contrast agents. Ultrasound can be used to measure the size of the liver, evaluate it for various masses and cysts, evaluate and stage parenchymal disease, and provide guidance for biopsies. This chapter will not cover biliary pathology because it is covered in another chapter. Liver transplants are covered in another chapter as well as in another book in this series.

ANATOMY

Embryology

Early in the fourth week of fetal development, the liver, gallbladder, and bile duct system develop from the endoderm. The hepatic diverticulum, also called the liver bud, develops from the ventral aspect of the foregut of the endoderm and gives rise to the parenchyma of the liver as well as the gallbladder and bile ducts. During week 5, the diverticulum differentiates into the origin of the cystic duct and the gallbladder in the caudal portion and the two endodermal cellular buds begin forming the right and the left hepatic lobes.¹, ² and ³ These solid cell buds grow into columns or cylinders that branch and form networks, which will envelope the vitelline and umbilical veins and become the liver sinusoids. The columns of endodermal cells in the liver parenchyma grow into the surrounding mesoderm. The mesoderm provides the hemopoietic tissue, which forms blood cells, until the bone marrow and spleen take over the process in late fetal life, and the connective tissue for the portal tracts and the fibrous liver capsule that becomes Glisson capsule.¹^,³ As the terminal branches of the right and left hepatic lobes canalize, the bile duct system is formed. The development of the Kupffer cells starts in the yolk sac and they will eventually migrate to the fetal liver.

Both lobes are equal in size until the beginning of the sixth week, at which time the right lobe (RL) becomes larger, with the caudate and quadrate lobes developing from the RL. The left lobe actually undergoes some degeneration. At week 6, the liver fills most of the abdominal cavity and, relative to other organ development, the liver becomes less active.¹^,²

Hemopoiesis takes place in the liver at week 6, peaks at 12 to 24 weeks, and ceases at birth.¹^,⁴ At week 10, lymphocyte formation occurs in the liver, which also ceases at birth. Coagulation factors are manufactured at 10 to 12 weeks and bile is produced by 13 to 16 weeks,¹ but the fetal liver does not take part in digestion until after birth.⁵

Oxygenated blood and nutrients are delivered to the fetus through the umbilical vein, which ascends and divides into two branches.⁶^,⁷ The left branch joins the portal vein and enters the liver and the right branch, the ductus venosus, flows directly into the inferior vena cava (IVC), bypassing the liver⁵^,⁸ (Fig. 7-1). Normally, both of these vessels deteriorate into fibrous cords sometime after birth. The left umbilical vein becomes the ligamentum teres, or round ligament, and the ductus venosus becomes the ligamentum venosum. Both the ligamentum teres and the ligamentum venosum can become recanalized as collateral vessels in patients with portal hypertension.⁸

Location and Size

The liver fills the right hypochondrium, epigastric region, and the left hypochondrium as far as the mammillary line. Most of the RL and usually the entire left lobe are protected by the ribs; therefore, intercostal scanning may be needed to visualize the entire liver. The liver can provide an acoustic window through which the upper abdomen and retroperitoneum may be imaged (Fig. 7-2A, B). The liver is wedge or triangular in shape with its base to the right and its apex to the left. Sonographically, the liver displays a medium-level homogeneous echo pattern owing to the nonspecular reflections from the hepatocytes. Interspersed within the parenchyma are tubular, fluid-filled structures representing the branches of the portal and hepatic veins. The liver is usually more echogenic, or it can also appear to be isoechoic, to the normal renal cortex (Fig. 7-3A, B). The liver is less echogenic than the normal pancreas and spleen. Disease processes can change these relationships. An example is when a normal right kidney appears to be
more echogenic than the liver in a patient with hepatitis, whose inflamed liver is abnormally hypoechoic.

FIGURE 7-1 Fetal circulation. The umbilical vein carries oxygenated blood from the placenta to the fetus, ascends the fetal abdomen, and courses toward the liver. A portion of blood flow is allowed to bypass the fetal liver via the ductus venosus. After birth, both veins close and exist as ligaments; the umbilical vein becomes the ligamentum teres and ductus venosus becomes the ligamentum venosum.

The liver varies somewhat in shape and size, depending on the patient’s body type, the size of the left lobe, and the length of the RL. The weight of a normal liver varies but usually ranges from about 1,200 g in an adult female to about 1,600 g in an adult male.⁷ The weight of the liver is approximately 1/36th of the total body weight for an adult as compared to approximately 1/18th of the total body weight for an infant.⁹ The normal transverse measurement of the liver can range from 20 to 22.5 cm, the anteroposterior (AP) measurement from 10 to 12.5 cm, and the length
from 13 to 15.5 cm, although some references go as high as 17 cm.¹¹ An AP measurement can be obtained on the same image as the length if needed. The length of the liver is obtained by measuring the liver from the diaphragm to the tip of the RL at the right midclavicular level, which is an imaginary vertical line that goes through the middle of the clavicle.¹⁰^,¹¹ The liver’s size can increase with increased height and body surface area and decrease with age.¹⁰ Liver length is needed to determine if hepatomegaly is present.

FIGURE 7-2 Liver location. A: The liver occupies the right hypochondrium, the greater part of the epigastric region, and extends in varying degrees into the left hypochondrium as far as the mammary line.³ The lateral segment of the left lobe and the length of the right lobe determine the contour and shape of the liver. Overall, the liver can be described as irregular, hemispheric,² or wedge-shaped.³ B: The relationship of the liver to surrounding anatomy is illustrated in a lateral, sagittal section.

FIGURE 7-3 Normal sonographic anatomy. A: sagittal image of the right lobe (RL) of the liver demonstrating the normal increased echogenicity relationship between the normal liver and normal right kidney (RK). B: A transverse image demonstrating the normal homogeneous echo pattern of the liver and the three main hepatic veins, the right hepatic vein (RHV), the middle hepatic vein (MHV), the left hepatic vein (LHV), and the inferior vena cava (IVC).

Kratzer and coworkers did an extensive sonographic liver measurement study on 2,080 subjects. They found that the average liver length at the midclavicular line was 14.0 ± 1.7 cm. The average length for male subjects was 14.5 ± 1.6 cm and for female subjects 13.5 ± 1.7 cm.¹² Their technique allows for easy assessment and accurate follow-up examinations. They also demonstrated that body mass index, height, sex, age, and frequent alcohol consumption in men influenced liver size.¹²

Perihepatic Relationships

The liver is an intraperitoneal organ that is covered by a capsule that is composed of two adherent layers. One layer is an outer serous layer that is derived from the visceral peritoneum and covers the liver except at the bare area near the diaphragm, the porta hepatis, and the area where the gallbladder is attached to the liver. The inner layer is a dense, fibroelastic connective tissue called Glisson capsule, which is named after the British physician and anatomist Francis Glisson, who was the first person to describe the
layer of connective tissue that covers the entire liver and each lobule. Glisson capsule contains blood, lymphatic vessels, and nerves and is highly echogenic by sonography.¹⁰^,¹³^,¹⁴ Distention of the capsule from liver disease or swelling can cause pain, and lymphatics may ooze fluid into the peritoneal space.¹³ Glisson capsule also ensheaths the portal triad, which consists of a branch of the hepatic artery, portal vein, and bile duct, which explains why the portal triad has echogenic borders.

FIGURE 7-4 Normal anatomy. A: Anterior surface. The ligamentum teres begins at the umbilicus and courses within the falciform ligament to a deep notch called the umbilical notch, which is located on the anterior surface of the liver. The falciform ligament divides the liver into right and left anatomical lobes and will become the coronary ligaments. Opposite the cartilage of the ninth rib is the fossa for the gallbladder fundus.⁹ B: Posterior surface. The posterior portion of the liver is round and broad on the right and narrow on the left.³ The caudate lobe lies between the inferior vena cava (IVC) and the ligament venosum, which is not marked on this image.³^,⁹ The posterior surface is in direct contact with the diaphragm and is attached by loose connective tissue. Most of the liver is covered by peritoneum except for the bed of the gall bladder, the porta hepatis, and where the liver is in direct contact with the diaphragm called the bare area. The bare area is bounded by the superior and inferior reflections of the coronary ligament, which connect the liver to the diaphragm.⁹ C: Posterior inferior view of visceral area: The right subphrenic space is seen between the right lobe of the liver and the inferior surface of the diaphragm. The left subphrenic space is seen between the diaphragm and the spleen. From lateral to medial, the right lobe has three impressions—the colic impression, which is a flattened or shallow area for the hepatic flexure; more posterior is the larger and deeper impression for the right kidney; and lying along the neck of the gallbladder, the duodenal impression is a narrow, poorly marked area.³ On the left, the gastric impression for the ventral surface of the stomach is a large, hollow area extending to the liver margin. D: Visceral surface. The visceral surface is concave and faces posterior, caudal, and to the left.³^,⁹ The caudate process is just anterior to the IVC and connects the caudate lobe to the right lobe.⁹ On this image, the ligamentum venosum is seen with the caudate lobe located between the ligamentum venosum and the IVC. The portal triad as it enters the liver via the porta hepatis is illustrated.

The external surfaces of the liver are described as the diaphragmatic and visceral surfaces. The diaphragmatic surface is the anterosuperior surface of the liver and is smooth and convex, fitting beneath the curvature of the diaphragm. The posterior aspect of the diaphragmatic surface is not covered by the visceral peritoneum and is called the bare area. The bare area is a small triangular area where the liver connects to the diaphragm, and although it is not covered by the visceral peritoneum, it is covered by Glisson capsule. The bare area lies between the anterior and posterior folds of the coronary ligament and is clinically important because it represents an area where disease, such as an abscess or tumor, can spread from the abdominal cavity to the thoracic cavity because the barrier in the form of the visceral peritoneum is absent⁹^,¹⁵ (Fig. 7-4 A-D).

The visceral surface of the liver faces inferiorly and posteriorly with its shape determined by the surrounding organs. It is uneven and concave and is covered by the peritoneum except in the fossa of the gallbladder, the
porta hepatis, and the IVC groove. It is in contact with the esophagus, the stomach including the pylorus, the first part of the duodenum, the right hepatic flexure, the transverse colon, the lesser omentum, the gallbladder, the right kidney, and the right adrenal gland.

Ligaments

The liver is tethered to the undersurface of the diaphragm, the anterior wall of the abdomen, the lesser curvature of the stomach, and the retroperitoneum by eight ligaments, seven of which are either parietal or visceral peritoneal folds and one of which is a round, fibrous cord. These ligaments are as follows: the coronary, falciform, ligamentum teres (round ligament), ligamentum venosum, right and left triangular, gastrohepatic, and hepatoduodenal ligaments.¹⁵ The largest of these ligaments is the coronary ligament. They are described in Table 7-1 and can be identified on Figures 7-4 and 7-5. Understanding the location of these various ligaments can help in identifying the location of various pathologies and fluid collections.

Lobar Anatomy

The lobes of the liver can be described based on their anatomic or external landmarks or their functional anatomy, which is based on the portal and hepatic veins. Because the author may not specify which method is being used, the literature can be confusing and may appear to be contradictory. The next section presents each method separately. The sonographic images are presented in the segmental division because sonographers evaluate and document the liver using internal landmarks.

TABLE 7-1 Ligament Attachments to the Liver

Ligament	Description
Coronary	The coronary ligament attaches the superior surface of the liver to the inferior surface of the diaphragm. The coronary ligament consists of an anterior and a posterior layer that create a triangular area that is devoid of peritoneum which is called the bare area of the liver. The anterior layer is formed by the reflection of the parietal peritoneum and is continuous with the right layer of the falciform ligament. The posterior layer is reflected from the caudal margin of the bare area onto the right adrenal gland and right kidney and is sometimes referred to as the hepatorenal ligament.¹⁵ The anterior and posterior folds unite to form the triangular ligaments.¹⁵^,¹⁶
Falciform	The term falciform ligament is derived from Latin, meaning sickle shaped. It is a broad and thin fold of peritoneum that anchors the anterior surface of the liver to the anterior abdominal wall. It is used to separate the anatomic right and left liver lobes. It extends from the liver to the abdominal wall between the diaphragm and umbilicus.⁹^,¹⁵^,¹⁶ At its base or free edge, the ligamentum teres is released from between its layers.¹⁵
Ligamentum teres	The ligamentum teres, or round ligament, is a fibrous cord that is the remnant of the left umbilical vein.⁹^,¹⁵ The round ligament divides the left lobe into medial and lateral sections. It ascends from the umbilicus in the free margin of the falciform ligament into the umbilical fissure where it is in continuity with the ligamentum venosum and joins the left branch of the portal vein.⁹
Ligamentum venosum	The ligamentum venosum is the obliterated ductus venosus and is usually attached to the left branch of the portal vein and can be in continuance with the ligamentum teres within the left intersegmental fissure. The ligamentum venosum is invested by the peritoneal folds of the lesser omentum within a fissure between the caudate and left lobe.
Triangular	The right and left triangular ligaments are named because of their triangular shape. They are formed by the apposition of the upper and lower ends of the coronary ligament and extend from the diaphragm of the liver.⁹ The right triangular ligament attaches the right lobe of the liver to the diaphragm.¹⁵ The left triangular ligament is the larger of the two. It lies anterior to the esophagus and connects the posterior part of the upper surface of the left lobe to the diaphragm.⁹
Gastrohepatic	The gastrohepatic ligament connects the liver to the lesser curvature of the stomach. It is composed of two folds of visceral peritoneum and originates on the undersurface of the liver. It extends from the fissure of the ligamentum venosum and porta hepatis; courses caudally to attach to the lesser curvature of the stomach and to the first portion of the duodenum; and, together with the hepatoduodenal ligament, forms the lesser omentum.⁵^,¹⁵
Hepatoduodenal	The hepatoduodenal ligament is a thick anatomical structure wrapped in the peritoneum that constitutes part of the lesser omentum. It extends between the porta hepatis and the superior part of the duodenum. The opening behind the free edge of the hepatoduodenal ligament is the epiploic foramen or foramen of Winslow, which is the only communication between the lesser sac and the peritoneal cavity.⁹ The hepatoduodenal ligament encloses the portal triad to protect it because it provides the blood supply to the liver and drains the bile into the duodenum.

Anatomic Division

The anatomic division of the liver is based on external markings that divide the liver into right, left, caudate, and quadrate lobes. This method uses the falciform ligament on the anterior surface to divide the liver into its left and right lobes and considers the caudate and quadrate lobes as part of the RL. A simulated “H” configuration on the visceral surface has the ligamentum venosum and the ligamentum teres separate the caudate and the quadrate lobes from the left lobe, the porta hepatis separates the caudate from the quadrate, and the main lobar fissure (MLF) separates the caudate and the quadrate from the RL (Fig. 7-6).

Right Lobe

The RL occupies the right hypochondrium and is six times larger than the left lobe with this method.⁵ It is separated from the left lobe by the falciform ligament on its anterior surface and by the left intersegmental fissure on its visceral
surface.¹⁶ It is somewhat quadrilateral. The posterior surface is marked by three fossae: the porta hepatis, the gallbladder, and the IVC.¹⁷

FIGURE 7-5 Ligaments. A: The gastrohepatic ligament originates on the undersurface of the liver and courses caudal to attach to the lesser curvature of the stomach and the first portion of the duodenum. The hepatoduodenal ligament is located on the right free edge of the gastrohepatic ligament, surrounds the portal triad, and forms the anterior boundary of the epiploic foramen or the foramen of Winslow. B: Enlarged cutaway view of the hepatoduodenal ligament showing the portal triad.

FIGURE 7-6 Anatomic division. The “H” configuration on the visceral surface of the liver is as follows: An imaginary line from the gallbladder fossa to the inferior vena cava (IVC) fossa makes the right vertical limb. This separates the right lobe from the caudate and quadrate lobes. The left vertical limb is a line created by the falciform ligament and the ligamentum venosum and separates the left lobe from the caudate and quadrate lobes.⁹. The transverse limb is the porta hepatitis and separates the caudate and quadrate lobes. The gallbladder fossa is shallow and oblong, extending from the inferior margin to the right border of the porta hepatis.⁹ The IVC fossa is a short, deep depression between the caudate lobe and the right lobe.

Caudate Lobe

The caudate lobe (CL) is anatomically distinct from the left and right lobes and is situated on the posterosuperior surface of the RL opposite the 10th and 11th thoracic vertebrae. It is located between the IVC posteriorly and the ligamentum venosum anteriorly.¹⁸^,¹⁹ The ligamentum venosum separates the caudate from the left lobe. The left margin of the caudate forms the hepatic boundary of the superior recess of the lesser sac. The caudate process is a small elevation of hepatic tissue that extends obliquely and laterally, from the lower aspect of the CL to the undersurface of the RL. It is situated behind the porta hepatis and separates the gallbladder fossa from the commencement of the fossa for the IVC. The papillary process is an anteromedial extension of the CL, which may appear separate from the CL and mimic lymph nodes.¹⁰^,¹⁵ Physiologically, the CL is considered independent from the liver vasculature because it has its own arterial supply and venous drainage. Blood drains from the CL directly into the vena cava via the small caudate veins.⁹

Quadrate Lobe

Anatomists describe the quadrate lobe as a distinct lobe, but it is physiologically and sonographically the same as the medial segment of the left lobe. The quadrate lobe is located on the undersurface of the liver between the middle and the left hepatic vein. Situated on the visceral surface, it is bounded posteriorly by the porta hepatis, anteriorly by the inferior margin of the liver, and laterally by the gallbladder fossa on the right and the fissure for the ligamentum teres on the left.¹⁵

Left Lobe

The left lobe is situated in the epigastric and left hypochondriac regions. Anatomically, it is separated from the RL by the falciform ligament on its anterior surface. On the visceral surface, the fissure for the ligamentum teres separates it from the quadrate lobe, and the fissure for the ligamentum venosum separates it from the CL.¹⁵ The left lobe is flatter and smaller than the right and can vary in size. Its superior surface is slightly convex, is molded to the diaphragm, and tapers off to the left at about the left mammary line.⁹^,¹⁵

Sonographic Segmental Division

Ultrasound can easily divide the liver into three lobes and four segments using the main lobar fissure, the hepatic
veins, and the ligamentum venosum and ligamentum teres (Fig. 7-7A). The lobes and segments are the RL, with an anterior and a posterior segment, the left lobe, with a medial and a lateral segment, and the CL.¹⁵ A combination of scanning planes that includes transverse, oblique, and parasagittal is needed to delineate the landmarks to identify the lobes and segments.

Right and Left Lobes

The MLF is a line that connects the gallbladder and the IVC and contains the middle hepatic vein (MHV). It is used to separate the liver into right and left lobes (Fig. 7-7B). It is seen sonographically as an echogenic line that runs obliquely between the neck of the gallbladder and right portal vein (RPV) (Fig. 7-7C).

The right intersegmental fissure divides the RL into its anterior and posterior segments. The sonographic landmark for the right intersegmental fissure is the right hepatic vein (RHV) (Fig. 7-7D-F).

The left intersegmental fissure divides the left lobe into medial and lateral segments. The sonographic landmarks used to define this fissure are the left hepatic vein (LHV); the ascending branch of the left portal vein (LPV); and more inferiorly, the hyperechoic ligamentum teres (Fig. 7-7G-J). In patients with ascites, the externally located falciform ligament may be a visible landmark for separation of the medial and lateral segments of the left lobe (Fig. 7-7K).

The sonographer should understand that the hepatic veins are intersegmental—that is, they run between the segments—and that the portal veins are intrasegmental, because they will travel within the segments, except for the ascending portion of the LPV, which runs in the left intersegmental fissure (Fig. 7-7L). The RPV divides into an anterior segmental branch and a posterior segmental branch, supplying blood to each respective segment (Fig. 7-7M). The LPV divides into medial and lateral segment branches supplying blood to their respected segments (Fig. 7-7N). Both portal veins and hepatic veins have distinguishing features by sonography that enable differentiation between them (Table 7-2).¹⁰^,¹⁷^,²⁶

Caudate Lobe

The CL is located in the posterior aspect of the liver and corresponds to the anatomic CL. Sonographically, three anatomic landmarks identify the CL. The anterior border of the CL is the fissure for the ligament venosum, which appears as a hyperechoic line that separates the CL from the left lobe, the IVC runs along the posterior aspect of the CL and the main portal vein (MPV) is located at the inferior aspect of the CL, separating it from the head of the pancreas (Fig. 7-7O, P).¹⁵^,¹⁶^,¹⁹

The CL is functionally distinct from the right and left lobes because it has its own bile ducts and receives its blood supply from both right and left portal and hepatic arterial branches.¹⁰^,¹⁹ It is drained by short venous channels that extend from its posterior aspect and drain directly into the IVC (Fig. 7-7Q).¹⁹ This independent blood supply has significant clinical implications that will produce changes in the size of the lobe with certain pathologies.²⁰^,²¹ The portal veins and hepatic arteries of the CL have a short intrahepatic course, which is not as readily affected by hepatic fibrosis. CL enlargement and RL shrinkage are seen in patients with cirrhosis and may be attributed to the discrepancy between blood perfusion of the two lobes.²² CL enlargement is also seen in patients with Budd-Chiari syndrome, which is thrombosis of the hepatic veins, cavernous transformation of the portal vein, and end-stage primary sclerosing cholangitis, which is a long-term inflammation and scarring of the bile ducts.

Couinaud’s Hepatic Segment Classification

In 1957, Claude Couinaud (pronounced kwee-NO), a French surgeon, described a detailed method of liver segmentation, which has become the universal nomenclature for hepatic lesion localization.¹⁰ It is currently the most widely used system to describe functional liver anatomy. The Couinaud classification system creates eight functionally separate liver segments, counted in a clockwise fashion. Traditionally, the hepatic segments were numbered using Roman numerals I to VIII, but the Arabic numerals 1 to 8 are now preferred (Fig. 7-8A-F). The CL is segment 1, the left lobe makes up segments 2 to 4, and the RL makes up segments 5 to 8 (Table 7-3).¹⁰^,²³^,²⁴ The division is based on the hepatic and portal vein branches. Each of the eight segments has its own branch of a portal vein, hepatic artery, hepatic vein, and bile duct. This allows the surgeon to resect a segment of a hepatic lobe, allowing the vascular supply to the remaining lobes to be left intact. The hepatic veins provide the boundaries of each segment. In Couinaud’s segmental anatomy, the three planes of the right, middle, and left hepatic veins divide the liver vertically. The MHV lies in the MLF and divides the liver into right and left lobes. This vertical plane courses from the IVC to the gallbladder fossa and is also known as the Cantlie line. The portal plane is a horizontal plane where the portal vein bifurcates and further divides the liver into superior and inferior segments. These three vertical planes and one horizontal plane divide the liver into the eight segments as summarized in Table 7-3.¹⁰^,²³^,²⁴ These segmental divisions do not coincide completely with the lobar anatomy divisions because the quadrate lobe is now the medial segment of the left lobe, the anatomic left lobe is now the lateral segment of the left lobe, and the CL is considered a separate lobe.

The Couinaud classification system of eight independent functional segments is important for the sonographer to understand because computed tomography (CT) and magnetic resonance imaging (MRI) will report the location of liver masses based on these eight segments. If the CT report states that the mass is in segment V, the sonographer will know to concentrate on the RL between the RHV and the MHV and posterior to the RPV. If the CT report states that the mass is in segment III, the sonographer will know to look in the left lobe lateral to the LHV. When a liver mass is initially discovered on an ultrasound examination, the sonographer should try and determine which segment contains the mass.¹⁰^,²³ This can be difficult with ultrasound, and the sonographer may only be able to narrow the location down to the left medial or lateral lobe using the LHV or ligamentum teres, the right anterior or posterior segment using the RHV or the CL.

Anatomic Variations

Variations of the liver include variations in shape, variations in lobe size, thinning of the left lobe, congenital absence of the left lobe, diaphragmatic indentations called pseudofissures,

high posterior hepatodiaphragmatic interposition of the colon, and situs inversus (Fig. 7-9A-C).⁹^,²⁰^,²⁵ A common variant that can mimic hepatomegaly is called a Riedel lobe, which is a downward projection of the RL. (Note that the proper name is Riedel lobe and not Riedel lobe.) It is more common in women than in men. Sonographically, a Riedel lobe is identified as a finger-like or a tongue-like projection of the RL that extends past the ribs and may reach as far as the iliac crest²⁵ (Fig. 7-10A, B). A Riedel lobe can be felt clinically, and the patient may be referred for a liver ultrasound to rule out a liver mass or hepatomegaly. To differentiate it from a mass, the sonographer must observe consistency of the echotexture between the Riedel lobe and the rest of the RL. To differentiate it from hepatomegaly, the sonographer should note that the rest of the liver’s size appears normal, and that the lobe comes to a point, whereas with hepatomegaly, the lobe has a more rounded edge (also see Fig. 7-16F, G). In hepatomegaly, the RL of the liver can displace the right kidney downward and up toward the diaphragm whereas a Riedel lobe “skims” across the top of the kidney.

FIGURE 7-7 Segmental division. A: A “see-through” anterior to posterior profile. The dotted lines will be referenced in subsequent illustrations and sonograms. Segmental anatomy. B: An illustration through vertical plane B (Fig. 7-7A), which represents the main lobar fissure, which is seen sonographically between the gallbladder neck and the RPV and is used to divide the liver into its segmental right and left lobes. C: A parasagittal scan displays a portion of the MLF, seen as a linear echogenic line extending from the RPV to the GB separating the RL from the LL. D: An illustration through vertical plane C (Fig. 7-7A), the right intersegmental fissure, where the RHV courses between the right anterior and right posterior branches of the portal vein. E: A parasagittal scan through the RHV, which is the sonographic landmark dividing the right lobe of the liver into anterior and posterior segments. F: A transverse scan through the RHV dividing the liver into ASRL and PSRL.

FIGURE 7-7 (continued) G: An illustration through vertical plane A (Fig. 7-7A), the left intersegmental fissure, where the LHV divides the left lobe into lateral and medial segments. H: A parasagittal scan through the LHV and IVC. The caudate lobe is seen between the IVC and the LV. I: A transverse scan through the LHV dividing the left lobe of the liver into medial and lateral segments. J: LT (small arrows) is seen in the left lobe of the liver in the transverse plane as a rounded echogenic structure with an acoustic shadow. It serves as a landmark separating the MSLL and the LSLL of the left lobe. The LT should not be mistaken for a liver lesion. K: On this transverse image of a patient with cirrhosis and ascites, the falciform ligament (arrow) can be identified coursing between the anterior abdominal wall and the LLL which is very nodular. L: A transverse scan demonstrates the hepatic veins and liver segments. The MHV separates the right and left liver lobes. The LHV separates the MSLL from the LSLL. The RHV divides the ASRL from the PSRL.

FIGURE 7-7 (continued) M: A transverse image demonstrates the division of the RPV into anterior (ANT) and posterior (POST) branches. N: A transverse image demonstrates the division of the LPV into medial and lateral branches. O: A sagittal scan demonstrates the LSLL, which is delineated from the CL by a linear echogenic line representing the LV (arrow). P: The anatomy identified on this transverse scan includes the LSLL, which is delineated from the CL by the LV (arrow). Q: A parasagittal image demonstrates a small vein (arrows) draining directly from the CL into the IVC. ASRL, anterior segment of the right lobe; CL, caudate lobe; GB, gallbladder; IVC, inferior vena cava; LHV, left hepatic vein; LL, left lobe; LLL, left lobe of the liver; LPV, left portal vein; LSLL, lateral segment of the left lobe; LV, ligamentum venosum; LT, ligamentum teres; MHV, middle hepatic vein; MLF, main lobar fissure; MPV, main portal vein; MSLL, medial segment left lobe; PSRL, posterior segment right lobe; RAPV, right anterior portal vein; RL, right lobe; RHV, right hepatic vein; RPV, right portal vein.

TABLE 7-2 Sonographic Criteria for Differentiating the Portal Veins and Hepatic Veins¹⁰^,¹⁷^,²⁶

Origin and drainage	Observe the point of origin and drainage of the vessels. Portal vein branches can be traced back to the main portal vein, distinguishing them from the hepatic veins draining into the IVC.
Echogenic walls	The portal vein runs with branches of the hepatic artery and of a bile duct and is known as a portal triad. The portal triad is covered by Glisson capsule, which is highly reflective, making the walls of the portal vein appear to be hyperechoic in contrast to the liver parenchyma. By contrast, the hepatic veins are surrounded by parenchymal tissue and have rather imperceptible margins. Specular reflection may occur if the sound beam strikes a main hepatic vein wall perpendicularly, resulting in a high-amplitude, echogenic margin that will disappear when the insonation angle is <90 degrees.
Branching patterns	An angle is formed as vessels bifurcate. For the portal vein, its vessels branch such that the angle’s apex point toward the porta hepatis. For the hepatic veins, branching occurs such that the angle’s apex points toward the IVC and heart.
Caliber changes and Doppler signal	The direction of blood flow also dictates the caliber of the venous radicles. The caliber of the hepatic veins becomes greater as it courses toward the IVC and diaphragm. The caliber of the portal veins decreases further from its point of origin, the porta hepatis. The hepatic veins have a pulsatile waveform whereas the portal vein has a continuous waveform.
Segmental location	Hepatic veins are interlobar and intersegmental, coursing between lobes and segments. Portal veins are intrasegmental, coursing within lobar segments.
IVC, inferior vena cava.

Vascular System

The liver is a unique organ in that it receives a blood supply from two different sources. The hepatic artery supplies about 20% to 30% of the blood supply to the liver and 40% to 50% of oxygenated blood. The remaining 70% to 80% is supplied by the portal venous blood, which is nutrient rich and contains oxygenated blood, supplying 50% to 60% of the oxygenated blood owing to its greater volume. The portal vein and the hepatic artery mix their blood in the liver sinusoids, which are drained by the central hepatic vein (Fig. 7-11A-C).

Hepatic Arteries

The common hepatic artery supplies oxygenated blood to the liver, pylorus of the stomach, duodenum, pancreas, and gallbladder. It is the largest branch of the celiac axis or trunk and the only branch that courses to the right across the epigastric region of the abdomen. The common hepatic artery passes anterior to the pancreas, and then inferiorly to the right toward the first part of the duodenum. It gives off the right gastric artery, which will anastomose with the left gastric artery. The common hepatic artery then travels upward, lying to the left of the common bile duct and anterior to the portal vein. As it courses toward the porta hepatis, it gives off the gastroduodenal artery and then becomes the proper hepatic artery, terminating into the right and left hepatic arteries that will supply blood to the right and left lobes, respectively. The cystic artery arises off of the right branch and the middle hepatic artery usually arises from the left branch (Fig. 7-11D-H).

Portal Veins

The MPV measures approximately 8 cm in length and has a maximum diameter of 13 mm. It originates just to the right of the midline at the junction of the splenic vein and superior mesenteric vein (SMV) anterior to the IVC and posterior to the neck of the pancreas. It carries blood containing nutrients and toxins from the gastrointestinal (GI) tract, except for the lower section of the rectum, the pancreas, gallbladder, and the spleen. The MPV courses upward and toward the porta hepatis within the hepatoduodenal ligament and is posterior to the hepatic artery and the common bile duct. Before entering the liver, the MPV divides into a smaller LPV and into a larger RPV with each branch entering the liver separately (Fig. 7-11I).¹⁰^,²⁶ The LPV lies more anterior and superior to the RPV. The LPV can be divided into transverse and umbilical portions. The LPV, prior to its bifurcation, gives off a branch that supplies the medial segment of the left lobe¹⁰ and a branch for the lateral segment of the left lobe (Fig. 7-11J). Both are intrasegmental in their course.²⁶ Prior to the bifurcation is the umbilical portion of the LPV, named because in utero, the umbilical vein is attached at this point.⁹ The umbilical portion of the LPV provides blood to the CL through small branches that are not visualized sonographically. The size of the LPV and its angle of bifurcation with the MPV vary, depending largely on the size and configuration of the left lobe.¹⁷ The main branches of the LPV originate from the umbilical portion and supply liver segments 2, 3, and 4. The RPV bifurcates at various distances from the MPV to

supply the right anterior and right posterior intrahepatic lobar segments (Fig. 7-11K-N).⁹ The RPV divides into an anterior branch that supplies blood to segments 5 and 8, and a posterior branch that supplies blood to segments 6 and 7. Segment 1, the CL, is not considered to be part of either the right or left lobe and receives blood from multiple branches from both the left and right portal veins. The hepatic artery, portal vein, and intrahepatic duct course parallel to each other with hepatic and portal blood flowing into the liver and bile flowing in the opposite direction out of the liver (Fig. 7-11O). Intrahepatic ducts are not visualized routinely. If biliary radicles and portal venous radicles are imaged simultaneously side by side, the appearance, referred to as the parallel-channel sign, is used to diagnose biliary obstruction (Fig. 7-11P). Color or power Doppler imaging can distinguish the vessel from the bile duct. The biliary system is discussed in more detail in a later chapter.

FIGURE 7-8 Couinaud’s anatomy. A: An illustration of the eight segments and how they are identified in a clockwise fashion. The hepatic veins divide the liver vertically into four segments and the portal veins divide the liver horizontally creating eight segments. The caudate lobe is segment 1 and is seen on the posterior aspect of the liver, it is not seen in an anterior view. B: A cross-sectional illustration high in the liver at the level of the hepatic veins identifies the four superior segments in Couinaud’s anatomy (PS = segment 7, AS = segment 8, MS = segment 4a, and LS = segment 2). C: A cross-sectional illustration at a midlevel through the liver identifies the right and left portal vein branches that correspond with the horizontal boundary. D: A cross-sectional illustration low in the liver at the level of the gallbladder and ligamentum teres identifies the four inferior segments in Couinaud’s anatomy (PS = segment 6, AS = segment 5, MS = segment 4b, and LS = segment 3). E: A transverse scan at the level of the hepatic veins demonstrates the superior segments. F: A transverse scan through the gallbladder and ligamentum teres demonstrates the inferior segments.

TABLE 7-3 Couinaud’s Segmental Anatomy¹⁰^,²³^,²⁴

Caudate Lobe
Segment I	Caudate lobe is situated posteriorly and is anterior to the IVC and separated from the left lobe by the ligamentum venosum.
Left Lobe
Segment II	Lateral segment of left lobe located above (superior) the portal plane and lateral to the LHV
Segment III	Lateral segment of left lobe located below (inferior) the portal plane and lateral to the LHV
Segment IVa	Medial segment of left lobe located above (superior) the portal plane and between the MHV and LHV
Segment IVb	Medial segment of left lobe located below (inferior) the portal plane and between the MHV and LHV; includes the quadrate lobe
Right Lobe
Segment V	Anterior segment of right lobe located below (inferior) the portal plane and between the MHV and RHV
Segment VI	Posterior segment of right lobe located below (inferior) the portal plane and lateral to the RHV
Segment VII	Posterior segment of right lobe located above (superior) the portal plane and lateral to the RHV
Segment VIII	Anterior segment of RL located above (superior) the portal plane between the MHV and RHV
IVC, inferior vena cava; LHV, left hepatic vein; MHV, middle hepatic vein; RHV, right hepatic vein; RL, right lobe.

FIGURE 7-9 Situs inversus. A: Transverse scan on a newborn at midline demonstrating the liver in the left upper quadrant. B: Color Doppler image showing the inferior vena cava (IVC) on the left side of the abdomen and the aorta (Ao) on the right side. C: Parasagittal scan on the left side showing the right lobe of the liver and the right kidney.

FIGURE 7-10 A: An image of a Riedel lobe on a 36-year-old woman demonstrating this normal variant as an extension of liver tissue past the right kidney. B: Another example of a patient with a Riedel lobe and the liver measured 21.5 cm.

FIGURE 7-11 Vascular anatomy of the liver. A: Intrahepatic distribution of the hepatic arteries, hepatic veins, portal veins, and biliary ducts. An accessory or inferior right hepatic vein is illustrated draining directly into the IVC and is a variant identified in some patients. B: The vessels and ducts of the upper abdomen. C: A recumbent view of the relationship between the vessels and ducts of the upper abdomen.

FIGURE 7-11 (continued) D: A sagittal scan of the abdominal aorta (Ao), the celiac axis (CA), and the SMA. The celiac artery will curve back toward the liver while the SMA will run parallel to the aorta. E: A transverse midline scan images the CHA and SA as they come off of the CA. This appearance of CA, CHA, and SA is called the tail of a whale sign. The third branch of the CA, the LGA, is not seen. F: Color Doppler image of the CA and the CHA and SA. Because of the curviness of the vessels at times flow is going away from the transducer, blue signals, and then toward the transducer, red signals. G: A three-dimensional power Doppler image with grayscale subtraction displays the CA branching into the SA, CHA, and the least often detected third branch, the LGA. H: A lateral view of the same 3D data set offering better visualization of the LGA.

FIGURE 7-11 (continued) I: On this transverse image, the MPV can be seen entering the liver. J: This transverse scan demonstrates the LPV dividing into its medial and lateral branches. K: A transverse color Doppler image shows the RPV dividing into the anterior (ANT) and posterior (POST) branches. The posterior branch will be flowing away from the transducer toward the posterior aspect of the liver and blue is the correct color. L: An oblique view with color Doppler imaging the RPV and the LPV as they bifurcate demonstrating flow away from the transducer (blue) in the RPV branch and flow toward the transducer (red) in the LPV branch. IVC, inferior vena cava. M: A 3D reconstruction of the vessels at the porta hepatis with grayscale subtraction reveals the MPV, RPV, LPV, HA, and HV.

FIGURE 7-11 (continued) N: A side-by-side image of the portal vein with color Doppler image on the left and microflow imaging on the right demonstrating the branches coming off of the portal vein, which are not seen with conventional Doppler. With microflow imaging, slower flow and smaller vessels can be detected with better spatial resolution and improved sensitivity. O: An image showing the relationship of the CBD with the PV and HA. Both the CBD and HA should be anterior to the PV. P: The grayscale image on the left shows multiple tubular structures called the parallel-channel sign. The color Doppler image on the right shows that the parallel-channel sign represents dilated bile ducts, structures void of color, and normal portal veins, vessels with color. Q: The RHV, MHV, and LHV are seen in this transverse scan draining into the IVC. Transducer placement is at the sternum angling toward the patient’s head. R: On this transverse color Doppler image, all three hepatic veins are seen with hepatofugal flow, which represents flow exiting the liver as they drain into the IVC. S: A transverse oblique image through the right lobe demonstrating an ARHV and the RHV draining into the IVC. The middle and left hepatic veins are not seen in this image. Ao, aorta; ARHV, accessory or inferior right hepatic vein; CA, celiac artery; CBD, common bile duct; CHA, common hepatic artery; GB, gallbladder; GDA, gastroduodenal artery; HA, hepatic artery; HV, hepatic vein; IMV, inferior mesenteric vein; IRHV, inferior right hepatic vein; IVC, inferior vena cava; LGA, left gastric artery; LHV, left hepatic vein; LPV, left portal vein; LRA, left renal artery; LRV, left renal vein; MHV, middle hepatic vein; MPV, main portal vein; PHA, proper hepatic artery; PV, portal vein; RHV, right hepatic vein; RPV, right portal vein; RRA, right renal artery; RRV, right renal vein; SA, splenic artery; SMA, superior mesenteric artery; SMV, superior mesenteric vein; SV, splenic vein.

Hepatic Veins

The hepatic veins are best visualized on transverse scans by angling the transducer toward the patient’s head from a subcostal approach. An intercostal approach from the right can also be helpful to evaluate them. The hepatic veins drain directly into the superior aspect of the IVC and all three veins, the right, middle, and left, should routinely be demonstrated emptying into the IVC (Fig. 7-11Q-S).²⁷

The RHV is the largest of the three hepatic veins and is located in the right intersegmental fissure and is used to divide the right hepatic lobe into anterior segments 5 and 8 and posterior segments 6 and 7. The RHV drains segments 5, 6, 7, and 8. A common anatomical variant is an accessory inferior right hepatic vein (IRHV). There is controversy regarding the incidence based on autopsies ranging from 61.4% to 88%,²⁸ and based on sonography, color Doppler, and CT imaging; the incidence has been reported from 10% to 28.33%.²⁸ When identified, the IRHV is visualized on a transverse section below the RHV (Fig. 7-11A and S).¹⁰^,²⁹ Attempting to identify an IRHV variant can be clinically important for several reasons: (1) The entire main RHV is resected during a hepatectomy, and the RL can be preserved along with the hypertrophic IRHV. (2) Thrombus has been identified in the IRHV in patients with hepatocellular carcinoma (HCC). (3) Finally, the RL’s main drainage vein becomes the IRHV in patients with Budd-Chiari syndrome.²⁸^,²⁹ The MHV is located in the MLF, separates the right and left lobes, and drains segments 4 of the left lobe and segments 5 and 8 of the RL.¹⁰ The smaller LHV is located in the cephalic portion of the left intersegmental fissure and divides the left lobe into lateral and medial segments²⁷ and drains segments 2, 3, and 4. A common variant is for the MHV and the LHV to join and become a common trunk before emptying into the IVC.

Sonographic Distinction between Portal and Hepatic Veins

It is important to be able to differentiate between the portal and hepatic veins sonographically. The five criteria used to distinguish hepatic veins and portal veins are described in Table 7-2. The easiest way to differentiate between the two vessels is by spectral Doppler imaging because each vessel has its own distinct waveform.

Porta Hepatis

The porta (gate) hepatis (liver) is a fissure where the portal vein and hepatic artery enter the liver and the bile duct exits the liver.⁹ In the normal relationship of these three structures within the hepatoduodenal ligament, the bile duct is ventral and lateral, the hepatic artery is ventral and medial, and the portal vein is dorsal (see Fig. 7-11B, C).¹⁵

It is important to evaluate these structures and measure the bile duct in either a transverse or longitudinal section. To do this, the splenic vein should be located on a transverse section and followed to the right, where it is joined by the SMV and becomes the portal-splenic confluence (Fig. 7-12A). From the confluence, the MPV will course toward the liver and appear round. The transducer should be positioned at an oblique angle, approximately 45 degrees (from right shoulder to left hip), until the long axis of the MPV, bile duct, and hepatic artery are identified. A measurement of the bile duct should be made by placing the calipers along the inner wall to the opposing inner wall of the duct. The published values for the normal internal diameter of the bile duct vary from 4 to 8 mm. A transverse section through the portal triad creates what is called the Mickey Mouse sign (Fig. 7-12B). This is just a quick overview, and in-depth knowledge of the biliary system can be acquired from Chapter 8.

The bile duct and hepatic artery may be confused because of their proximity, their similar internal diameter, and common anatomic variations of these structures. Color Doppler imaging can help in distinguishing the bile duct from the hepatic artery owing to the presence of flow in the artery and absence of flow in the bile duct (Fig. 7-12C). In addition, Berland and colleagues²⁹ found several reliable sonographic signs to differentiate the bile duct from the hepatic artery, including evaluating the porta hepatis with Doppler techniques:

Only pulsations should be exhibited by an artery or a vein.
An artery can indent the wall of a duct or a vein, but the reverse is not true. This is probably because of the lower venous and ductal pressures and the thicker, less easily deformed arterial wall.
The duct can occasionally decrease several millimeters in caliber during an examination and can have various calibers along its course, whereas arteries are uniform in caliber.
The artery may not parallel the portal vein or may do so only for a short distance, whereas the duct parallels the portal vein closely.
Arteries may be tortuous and loop in and out of the scanning plane.
Arteries produce pulsatile Doppler signals, veins produce continuous Doppler signals, and ducts produce no signal.

FIGURE 7-12 A: Transverse section demonstrating the splenic vein (SV) and portal-splenic confluence (PSC). Locating the confluence at the level of the pancreas helps identify the origin of the main portal vein (MPV). B: An image of a portal triad showing the hidden “Mickey Mouse” sign. The MPV represents the face; the bile duct (BD) the right ear; and the hepatic artery (HA) the left ear. C: A color Doppler image of the hidden “Mickey Mouse” sign showing flow in the MPV and HA and no flow in the BD. Ao, aorta; SMA, superior mesenteric artery.

Microscopic Structures

Hepatic lobes are made up of the basic functional unit of the liver, which is the liver lobule.⁵^,⁶ The liver parenchyma is made up of 50,000 to 100,000 individual lobules (Fig. 7-13A, B).⁴ Within each lobule, small bile canaliculi lie adjacent to the cellular plates and receive the bile produced by the hepatocytes to carry it toward the bile duct branches in the triad regions (Fig. 7-13C).⁴^,⁶^,¹³ These branches open into the interlobular bile ducts accompanying the hepatic artery and portal vein, except that bile flows in the direction opposite to that of blood in these vessels.⁴^,⁶ Bile ducts join other bile ducts and eventually form two main trunks, the right and left hepatic ducts, which eventually join to become the common hepatic duct.⁶^,⁷

FIGURE 7-13 Microscopic anatomy. A: An enlarged sectional cut of the liver shows the hexagonal shape of its lobules. Each lobule measures several millimeters in length and 0.8 to 2 mm in diameter.⁴^,⁹ B: The arrows indicate the direction of blood flow on this representation of one liver lobule. Constructed around a central hepatic vein, each lobule is composed principally of many cellular plates, or hepatocytes, the functional cells of the liver. The cellular plates radiate centrifugally from the central hepatic vein like wheel spokes.⁴ Hepatocytes are capable of regenerating, which allows damaged or resected liver tissue to regrow.¹³ A lobule has six corners. At each corner is a portal triad, so named because three basic structures are always present: a branch of the hepatic artery, a branch of the portal vein, and a bile duct.⁶^,⁷ C: An enlarged schematic view of a small portion of one liver lobule illustrates the sinusoids and portal triad. Sinusoids are small capillaries that have a highly permeable endothelial lining located between the cellular plates. The sinusoids receive a mixture of portal venous and hepatic arterial blood.⁴^,¹³ The blood drains into the central hepatic vein in the middle of each lobule and flows into the interlobular hepatic veins.⁴^,¹³ Unlike other capillaries, sinusoids are also lined with phagocytic cells known as Kupffer cells.⁵^,⁶^,¹³ Kupffer cells belong to the reticuloendothelial system and function to remove foreign substances, such as bacteria and depleted white and red blood cells, from the blood.⁵^,⁶ The Disse space, located between the endothelial lining and the hepatocyte, drains interstitial fluid into the hepatic lymph system.⁴^,¹³ Small bile canaliculi are adjacent to the cellular plates and receive the bile produced by the hepatocytes.⁴^,¹³

PHYSIOLOGY

The liver is an organ essential to life and performs more than 500 separate functions.⁴^,¹³ A single liver cell is so diversified in its activities that it is analogous to a factory for many chemical compounds, a warehouse with short- and long-term storage capabilities, a power plant producing heat, a waste disposal plant excreting waste, and to a chemistry lab regenerating tissue that has not been too severely damaged. These functions are carried out by three types of cells in the parenchyma: the hepatocyte, which carries out most metabolic functions; the biliary epithelial cells, which line the biliary system, bile ducts, canaliculi, and gallbladder; and the Kupffer cells, which are phagocytic and belong to the reticuloendothelial system.⁴

It is not necessary to know these liver functions in great detail to obtain quality sonograms; however, because hepatic diseases alter these functions and produce identifiable clinical manifestations, it is important to have a basic understanding of some normal functions (Table 7-4).²^,⁴, ⁵, ⁶, ⁷, ⁸ and ⁹^,¹³

TABLE 7-4 Hepatic Function²^,⁴, ⁵, ⁶, ⁷, ⁸ and ⁹^,¹³

Bile formation and secretion	Bilirubin, or bile pigment, is a major end product resulting from the breakdown of hemoglobin by Kupffer cells and other reticuloendothelial cells. Bilirubin, bound to plasma protein, travels via the bloodstream to the liver, where it is conjugated (i.e., made water soluble) and excreted into bile. Bile is produced continuously by the hepatic cells at a rate of 700-1,200 mL a day. Bile salts are formed from cholesterol in the hepatic cells, and they emulsify fats and assist in the absorption of fatty acids from the intestinal tract. Calculus formation occurs if the bile salt content is abnormally high owing to cholesterol precipitation.
Carbohydrate metabolism	The liver acts as a glucose buffer. It removes excess glucose from the blood, stores it, and returns it to the blood when the glucose concentration begins to fall. Functions of carbohydrate metabolism include (1) glycogenesis, the conversion of glucose to glycogen for storage; (2) glycogenolysis, the reduction of glycogen to glucose; and (3) gluconeogenesis, formation of glycogen from noncarbohydrates such as protein, amino acids, and fatty acids, which maintains a relatively normal blood glucose concentration.
Fat metabolism	Fatty acids are a source of metabolic energy. Approximately 60% of all preliminary breakdown of fatty acids occurs in the liver. Functions of fat metabolism include (1) beta-oxidation of fatty acids and formation of acetoacetic acid, a soluble acid that passes from the liver cells into the extracellular fluid; (2) formation of lipoprotein by synthesis of fat from glucose and amino acids; (3) formation of cholesterol, which forms bile salts and phospholipids; and (4) conversion of proteins and carbohydrates to fat to be transported as a lipoprotein for storage in the adipose tissue.
Protein metabolism	Protein metabolism functions include (1) deamination of amino acids, which is necessary before they can be used for energy or converted into carbohydrates or fats; (2) formation of urea by the liver, removing ammonia from the body fluid; (3) formation of approximately 85% of the plasma proteins (except approximately 45% of the gamma-globulins) at a maximum rate of 50-100 g/day; and (4) interconversions or synthesizing of amino acids and other compounds vital to the metabolism of the body.
Protein metabolism	The reticuloendothelial tissue performs an essential part in protein anabolism by synthesizing various blood proteins (prothrombin, bilinogen, albumins, accelerator globulin, factor VII) and other less important coagulation factors. Blood proteins are essential for normal circulation, because they maintain water balance, contributing to the blood’s viscosity.
Reticuloendothelial tissue activity	The activity of the reticuloendothelial tissue in the liver starts before birth with the production of blood cells, a process called hemopoiesis. By birth, this function is carried out by the bone marrow. Plasma has three major types of protein: albumin, globulin, and fibrinogen. All of the albumin and fibrinogen and 50% or more of the globulins are formed in the liver. The rest of the globulins are formed by the lymphatic and other reticuloendothelial systems. The function of albumins is to provide colloid osmotic pressure, which prevents plasma loss from the capillaries. Fibrinogen polymerizes into long fibrin threads during blood coagulation, forming blood clots to help repair leaks in the circulatory system. Globulins perform a number of enzymatic functions in the plasma. The principal function of globulins is to provide natural and acquired immunity against invading organisms.
	After a circulation time of approximately 120 days, red blood cells die. It is assumed that these cells simply wear out with age and rupture during passage through a tight spot in the circulatory system. The reticuloendothelial tissue of the spleen and the liver digests the hemoglobin released from the ruptured red blood cells. In this process, the iron from destroyed red cells is released back into the blood, bone marrow, or to other tissues.
	Large numbers of bacteria invade the body through the intestinal tract, passing through the mucosa into the portal blood. The sinuses of the liver where the blood passes are lined with Kupffer cells, which are tissue macrophages. Kupffer cells form an effective particulate filtration system. Almost all of the bacteria from the GI tract undergo phagocytosis.
Storage depot	The liver has the capacity to store enough vitamin A to prevent a deficiency for as long as 1-2 years⁴ and enough vitamin D and vitamin B₁₂ to prevent deficiency for 1-4 months. The liver also stores glycogen, fats, and amino acids and can metabolize them into glucose or vice versa, depending on the body’s needs.
Storage depot	Aside from iron in the hemoglobin, by far the greatest proportion of iron is stored in the liver in the form of ferritin. When the body becomes iron deficient, the ferritin releases iron. The liver is also the storage depot for copper and for some poisons that cannot be broken down or detoxified and excreted, such as dichlorodiphenyltrichloroethane.
Blood reservoir	Approximately 1,000-1,100 mL of blood flows from the portal vein through the liver sinusoids each minute, and another 350-400 mL flows through the hepatic artery. As a blood reservoir, the liver has the capacity to enlarge and store 200-400 mL of blood with a rise of only 4-8 mm Hg in hepatic venous pressure. If there is hemorrhage and large amounts of blood are being lost in the circulatory system, the liver releases its blood from that stored in the sinusoids to help compensate for this loss in blood volume.
Heat production	The liver, a significant metabolizer, produces heat as a result of its chemical reactions. On average, 55% of the energy of food ingested becomes heat during ATP formation. Even more heat is produced during the ATP cell formation process.
Detoxification	To a great degree, the liver is a detoxifier, converting chemicals, foreign molecules, and hormones to compounds that are not as toxic or biologically active. When amino acids are burned for energy, they leave behind toxic nitrogenous wastes that are converted to urea by the liver cells. These moderate amounts of urea are then easily removed by the kidney or sweat glands.
Lymph formation	Under resting conditions, the liver produces between one-third and one-half of all the body’s lymph.
ATP, adenosine triphosphate; GI, gastrointestinal.

LIVER FUNCTION TESTS

Liver function tests, commonly referred to as LFTs, are a group of blood tests that can tell the physician how the liver is performing under normal and diseased conditions. This group of tests is also referred to as a liver panel and includes total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST/ALT ratio, alkaline phosphatase (ALP), gamma-glutamyl phosphatase (GGT), and albumin. AST may also be referred to as aspartate transaminase or the older serum glutamic-oxaloacetic transaminase (SGOT), which is no longer used. ALT may also be referred to as alanine transaminase or the older serum glutamic-pyruvic transaminase (SGPT), which is also no longer used. Patients undergoing certain invasive procedures or surgery will have their bleeding times evaluated, especially if they have liver disease because one of the functions of the liver is to make clotting factors. These tests include prothrombin time (PT) and partial thromboplastin time (PTT). To evaluate for dilated biliary ducts is the main reason an ultrasound is ordered on a patient with increased LFTs. The presence of dilated ducts will mean that the patient will need to be treated surgically to relieve the obstruction. If the ducts are normal, then the reason for the increased values will be a medical condition such as hepatitis, fatty liver disease, overuse of over-the-counter drugs such as acetaminophen, prescription drugs such as statin drugs, alcohol abuse, and primary or metastatic disease. (The most common cause of acute liver failure in the United States is an overdose of acetaminophen, usually as a suicide attempt.) The most common laboratory tests are listed in Table 7-5.²⁶^,³¹, ³² and ³³ Normal reference ranges are not provided because they can vary by gender and age, and values can be updated periodically. The range of normal values used will be on the patient’s report next to their current value, with abnormal values indicated and clearly marked as high or low.

TABLE 7-5 Liver Function Tests²⁶^,³¹^,³³

Test	Explanation	Result	Clinical Indication
Bilirubin	It is formed in large part from heme of destroyed erythrocytes. Heme is converted to biliverdin and then another enzyme changes it into bilirubin (unconjugated). Unconjugated or indirect bilirubin is bound to albumin and transported to liver cells. The liver conjugates the bilirubin with glucuronic acid, making it soluble in water. Most of this conjugated bilirubin goes into the bile.	Indirect values are increased.	Body is making too much bilirubin, usually owing to an increase in red blood cell breakdown such as hemolytic anemia and hemolysis, or diseases that affect the liver’s ability to conjugate, such as Gilbert syndrome or Crigler-Najjar syndrome. Typically, causes of increased indirect values cannot be diagnosed with ultrasound.
	Conjugated or direct bilirubin is not excreted but remains in the blood. Bilirubin is conjugated by liver enzymes, becomes water soluble, and is excreted in feces and urine.	Direct values are increased.	Clinical indications include hepatocellular jaundice from hepatitis or cirrhosis; obstructive liver disease; intrahepatic cholestasis, alcoholic hepatitis, primary biliary cirrhosis, or posthepatic jaundice from lower biliary tract obstruction, biliary stones, pancreatic head pathology, especially cancer. Typically, causes of increased direct values can be diagnosed with ultrasound. Most laboratories report the total value and the direct (conjugated) value. The indirect (unconjugated) value is calculated by subtracting the direct value from the total.
ALT	It is a necessary enzyme in Krebs cycle for tissue energy production, with largest amounts in the liver, smaller amounts in the kidney, heart, and skeletal muscle. When damage to these tissues occurs, ALT increases. ALT is a rather specific indicator of hepatocellular damage. It is used in conjunction with AST to help distinguish between cardiac and hepatic damage. AST levels are very high and ALT levels are only mildly elevated with cardiac damage. ALT can differentiate between hemolytic jaundice when there is no rise in ALT and jaundice owing to liver disease with high ALT levels. Hepatitis, cirrhosis, Reye syndrome, and toxic drug treatment can be monitored with ALT.	Values are increased.	Clinical indications include liver cell damage owing to hepatitis, cirrhosis, or liver tumors; Reye syndrome, or biliary tract obstruction; other diseases involving the liver, heart failure, alcohol or drug abuse; its levels are elevated with some renal diseases, some musculoskeletal diseases, systemic lupus erythematosus, other conditions that cause trauma or hypoxia, and hemolysis. Ratio of AST to ALT can be meaningful. AST levels are higher in cirrhosis and metastatic carcinoma of the liver. ALT levels are usually higher in acute hepatitis, alcoholic liver disease, and nonmalignant hepatic obstruction.
AST	An enzyme found in all tissues, but largest amounts are present in in cells that use the most energy, such as liver, heart, and skeletal muscles. AST is released with injury to cells.	Values are increased.	In hepatitis, it is elevated before jaundice appears; cirrhosis, shock, or trauma may cause lesser elevation; other conditions include Reye syndrome and pulmonary infarction. Damaged cardiac cells have other correlating examinations. Ratio of AST to ALT is significant (see clinical indications for ALT).
ALP	This enzyme is found in the tissues of liver, bone, intestine, kidney, placenta; higher levels are normal with new bone formation in children and in pregnancy; it is normally excreted in bile.	Values are increased.	Clinical indications include biliary obstruction from tumors or space-occupying lesions, hepatitis, metastatic liver carcinoma, pancreatic head carcinoma, cholelithiasis, or biliary atresia; elevation may also occur from bone or kidney origin and from congestive heart failure owing to hepatic blood flow obstruction.
LDH	An enzyme in all tissues, LDH is normally not used for liver evaluation because other enzyme values are more specific. LDH₄ and LDH₅ are found in liver, skeletal, kidney, placenta, and striated muscle tissue.	Values are increased for LDH₄ and LDH₅.	Liver damage owing to cirrhosis, chronic viral hepatitis, etc.
GGTP or GGT	Responsible for the transport of amino acid and peptide across cell membranes, it is found chiefly in liver, kidney, and pancreas, with smaller amounts in other tissues. The test is the most sensitive indicator of alcoholism and is also sensitive to other liver diseases.	Values are increased.	Clinical indications include marked elevation in liver disease and posthepatic obstruction; moderate elevation with liver damage from alcohol, drugs, chemotherapy; elevation may also be owing to pancreatic, kidney, prostate, heart, lung, or spleen disease.
PT	Test used to determine pathologic deficiency of clotting factors due either to liver dysfunction or to absence of vitamin K.	Values are increased.	Bleeding disorder, correlated with obstructive disease, PT can be corrected with parenteral vitamin K; when correlated with parenchymal disease, scarred nonfunctioning liver tissue does not produce prothrombin.
Albumin	The smallest protein molecule, it makes up the largest proportion of total serum protein. It is almost totally synthesized by the liver. Albumin plays an important role in total water distribution or osmotic pressure because of its high molecular weight. With dehydration, albumin levels increase. A lack of albumin in the serum allows fluid to leak out into the interstitial spaces and into the peritoneal cavity causing ascites.	Values are decreased.	Chronic liver disease, especially cirrhosis; ascites from cirrhosis, right-sided heart failure, cancer, or peritonitis; other conditions related to the GI tract, inflammation, pregnancy, and aging.
Albumin		Values are increased.	Clinical indications include hemolysis, other conditions related to dehydration, exercise, anxiety, depression.
A/G ratio	Albumin divided by globulins equals the ratio. When evaluating liver disease, serum globulin is produced by the Kupffer cells and albumin is synthesized in the liver. In chronic liver disease, the A/G ratio is reversed where albumin is decreased and globulin is elevated.	Decreased total protein with decreased albumin and elevated globulin (reversed A/G ratio)	Chronic liver disease, especially cirrhosis, ascites from cirrhosis; right-sided heart failure, cancers, or peritonitis and other conditions related to the GI tract; and inflammation, pregnancy, and aging
AFP	A globulin formed in yolk sac and fetal liver, it is normally present only in trace amounts after birth; produced with primary carcinoma of the liver and certain types of testicular cancer.	Values are increased.	In nonpregnant adults, carcinoma of the liver, as in hepatocellular carcinoma; in the pediatric patient, hepatoblastoma
AFP, alpha-fetoprotein; A/G, albumin/globulin; ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGTP or GGT, gamma-glutamyl transpeptidase; GI, gastrointestinal; LDH, lactic dehydrogenase; PT, prothrombin time.