The Liver in Health

The characteristic¬†structure and organization of the liver enables it to perform vital roles in regulating, synthesizing, storing, secreting, transforming, and breaking down many different substances in the body. In addition, the liver’s ability to regenerate lost tissue helps maintain these functions, even in the face of moderate damage. This section of the module focuses on the structural aspects of the liver and its ability to regenerate.

Objectives

These objectives will focus your attention on expected learning outcomes. After you complete this section, you should be able to:

1. Describe the external structure of the liver and the blood vessels that supply and drain it.
2. Describe the arrangement of cells and blood vessels within the liver.
3. Briefly describe the process of hepatic regeneration.
4. Identify and briefly describe the major functions of the liver.

Key Concepts

1. The liver is located in the right upper quadrant of the abdominal cavity and comprises right and left lobes.

2. The liver receives a unique dual blood supply: systemic (body) via the hepatic artery and portal (gut) via the portal vein.

3. Microscopically, the liver is organized into structural units, or lobules, with six peripheral portal triads and a central vein.

4. One of the unique capacities of the liver is its ability to regenerate after partial removal or damage, although severe damage can lead to irreversible scarring.

5. The liver is important in the synthesis and secretion of key proteins (such as albumin and blood clotting proteins) and the storage of glucose and many vitamins and minerals.

6. Bile, which is important for the digestion and absorption of fats, is synthesized by the liver and enters the intestine via the bile ducts.

7. The liver plays a major role in the purification, transformation, and clearance of waste products (such as ammonia), drugs, and toxins.

A. Structure

The liver, the largest organ in the body, is located below the diaphragm in the right upper quadrant of the abdominal cavity, as shown in Figure 1; it is sheltered by the rib cage. In an adult, the liver normally weights about 3 pounds and extends approximately from the right fifth rib to the lower border of the rib cage (along an imaginary line extending down from the middle of the collar bone). When the patient inhales, the liver edge may be felt 1 to 2 cm below the right edge of the rib cage.

Liver structure has several unique aspects. This section discusses its gross anatomy and blood supply, its cellular organization, and its capacity to regenerate.

1. Gross Anatomy. Figure 2 shows the gross anatomy of the liver. Visual examination reveals that the liver is separated into two lobes, the right and the left (Figure 2a), separated by the falciform ligament. The right lobe is about six times the size of the left and contains two lesser lobes (Figure 2b).

The porta hepatis is the entry way for supplying blood vessels (the portal vein and the hepatic artery) as well as the exit site of ducts that drain bile formed in the liver. Bile leaves the liver via the right and left hepatic ducts, which then unite to form the common hepatic duct. The common hepatic duct in turn joins with the cystic duct from the gallbladder to form the common bile duct. Bile is stored in the gallbladder (a pear-shaped bag), and then it flows through the cystic duct into the common bile duct and empties into the intestine.

2. Hepatic Circulation.¬†Figure 3¬†summarizes the blood flow to and from the liver. As mentioned above, the liver receives a dual blood supply. The portal vein supplies blood (from the¬†portal system,¬†the network of veins and capillary beds draining the intestines and spleen) that is rich in nutrients and absorbed dietary substances but poor in oxygen. This provides 75% of the liver’s blood supply. The hepatic artery supplies oxygenated blood from the systemic circulation (aorta) and provides the remaining 25% of the liver’s blood supply.

Within the liver, both the portal vein and the hepatic artery branch within the lobes and eventually converge together into tunnels, or sinusoids Figure 4, that run parallel to rows of hepatocytes (liver cells). Sinusoids allow the exchange of substances between the blood and hepatocytes and merge to form central veins, which drain blood from the liver into the hepatic vein and then back to the right heart and lungs via the inferior vena cava.

3. Cellular Architecture.¬†The most abundant and metabolically active cells in the liver are the hepatocytes. They lie together in cords, or sheets, in close association with bile ducts and sinusoids¬†Figure 4. The sinusoids are lined by a single layer of endothelial cells, where oxygen, nutrients, and poisons are removed from the blood, and products made by hepatocytes for use elsewhere in the body are secreted into the blood.¬†Kupffer cells,¬†found in the sinusoids, are specialized “scavengers” that can engulf foreign particulate matter, worn-out blood cells, and bacteria.

Microscopically, the liver is organized into polyhedral units called lobules. When viewed on a cut section, a lobule is hexagonal with six portal triads at the periphery see Figure 5. Each portal triad contains a branch of the portal vein, a branch of the hepatic artery, and a bile duct, all held tightly together by a layer of hepatocytes, called a limiting plate, that surrounds the portal triad and separates it from the sheets of hepatocytes that radiate outward. In the center of the hexagon is a central vein. Blood flows through sinusoids from portal triads toward the central veins (peripheral to central), while bile flows outward toward the peripheral portal triads.

4. Regenerative Capacity. Hepatocytes rarely divide, but they have a unique capacity to reproduce in response to an appropriate stimulus, such as the removal of a portion of liver. This process involves controlled hyperplasia, or increased cell division, that usually restores the liver to within 5 to 10% of its original weight. Hepatic injury or partial removal leads to both systemic (e.g., in the blood and other tissues) and local (within the liver) release of growth factors that stimulate hepatocyte replication.

Because all hepatocytes can perform the necessary hepatic functions and all have an equal ability to replicate, the liver can undergo compensatory growth and restore its size. Liver regeneration plays an important role after surgical removal of a portion of liver (partial hepatectomy) and after injuries that destroy portions of the liver, such as viral, toxic, or ischemic damage. However, excessive damage can reach a “point of no return,” and normal tissue will be replaced with scar tissue. The liver’s ability to regenerate is also compromised by pre-existing or repeated liver damage or disease.

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