10.10: Liver

The liver is the largest gland in the body (Figure 10.1). It is made up of microscopic units called lobules, which resemble each other in structure and functioning (Figure 10.6). The liver cells making up each lobule are arranged in a radiating pattern, allowing blood from the periphery of the lobule to flow through large capillaries among the cells as it moves to the center of the lobule. These capillaries are called liver sinusoids

Figure 10.6 Structure of liver lobules. (Copyright 2020: Augustine G. DiGiovanna, Ph.D., Salisbury University, Maryland. Used with permission.)

Blood Flow

Blood enters the outer region of the lobule from arteries and veins at several points around the periphery of the lobule. The blood in the arteries comes from the heart and delivers oxygen and substances such as hormones from other organs to the liver cells. The blood in the veins comes from capillaries in the stomach, small intestine, large intestine, and pancreas. Blood from the spleen also passes through veins leading into the lobules. Since all these veins deliver blood to the liver rather than returning it to the heart, they are called the hepatic portal system (Figure 10.7).

Figure 10.7 The hepatic portal system. (Copyright 2020: Augustine G. DiGiovanna, Ph.D., Salisbury University, Maryland. Used with permission.)

Once blood from the arteries and the hepatic portal system has passed through the liver sinusoids, it is collected by a central vein at the center of the lobule. Blood from all the central veins moves into hepatic veins, which send it into a main vein going to the heart (the inferior vena cava). This arrangement of vessels permits the liver cells to adjust the contents of blood from digestive organs and the spleen before sending it to other parts of the body. The most abundant type of liver cells (hepatocytes) regulate the chemical makeup of blood. Other cells (Kupffer's cells) remove unwanted particles such as bacteria and damaged red blood cells from the blood (Figure 10.6).

Bile Flow

In addition to blood vessels, each lobule contains other small passageways called bile canaliculi (Figure 10.6). Bile, which is produced by hepatocytes, moves through the canaliculi to the periphery of the lobule, where it is collected into bile ducts. These ducts converge into one large duct, the hepatic duct, which carries the bile out of the liver (Figure 10.8). Bile in the hepatic duct may flow through the cystic duct for storage in the gallbladder or through the common bile duct into the small intestine.

Figure 10.8 Pathways for bile. (Copyright 2020: Augustine G. DiGiovanna, Ph.D., Salisbury University, Maryland. Used with permission.)

Functions

Each lobule contributes to every liver function. Many of these functions were mentioned earlier in this chapter. For example, the liver helps convert foods to a usable form by secreting bile and sending it to the small intestine. Bile is a complex mixture of materials, including water, cholesterol, bile salts, and bile pigments. The salts and pigments are mostly waste materials removed from the blood. For example, when red blood cells are destroyed, parts of their hemoglobin molecules are converted into bilirubin, which is secreted into the bile. Bile also contains the breakdown products of cholesterol.

Bile helps convert foods to a usable form by breaking up droplets of fat from foods. This emulsification process allows digestive enzymes to hydrolyze the fat more easily. Bile also assists with absorption by allowing some fat to be absorbed by the small intestine without being hydrolyzed.

Since blood from the stomach and intestines flows through the liver before it is sent to other parts of the body, the liver can remove excess amounts of nutrients. The liver uses these extra nutrients to manufacture substances that are at inadequate concentrations in the blood. For example, hepatocytes remove excess sugar that is absorbed after one eats a sweet dessert. Some of the sugar may be converted into other nutrients (e.g., fat) that may be in low supply in the food, and some may be stored in the liver as glycogen. Later, when blood sugar levels drop, the liver converts the glycogen back into sugar and returns the sugar to the blood. Thus, body cells receive fat and sugar at a steady rate.

Passing blood from the stomach and intestines through the liver also allows the hepatocytes to remove harmful or toxic materials that have been ingested and absorbed, such as alcohol from alcoholic beverages. The liver also removes unwanted materials produced by body cells, such as ammonia and bilirubin. Ammonia produced by intestinal bacteria and absorbed by the intestine is also removed from the blood. The liver converts the toxic ammonia to a much less dangerous material called urea. Finally, the liver removes many medications from the blood.

The liver has several other functions. One is helping to maintain proper and fairly stable blood pressure. Because it has so many large blood vessels, the liver can hold a large volume of blood. When blood pressure begins to drop, constriction of liver vessels sends more blood to the heart and arteries, restoring blood pressure to normal levels. Alternatively, relaxation and dilation of liver vessels remove some blood from circulation and lower blood pressure when it becomes too high.

Finally, the liver regulates many substances in the blood that are not considered nutrients. For example, it manufactures several substances (e.g., fibrinogen, prothrombin) that are involved in forming blood clots. It also makes many of the blood proteins that regulate the distribution of water in the body. Without adequate amounts of these proteins, much water leaves the blood and accumulates around body cells. This condition (edema) can cause uncomfortable swelling; when it occurs in the lungs, respiration is seriously impaired. Finally, the liver plays a major role in removing excess hormones from the blood. Important examples include aldosterone, which increases salt and water reabsorption by the kidneys, and sex steroids.

Age Changes

Aging causes little change in the overall structure of the liver, though there seems to be a slight decrease in size, the total amount of blood flow through the liver may decline, and liver cells become somewhat altered.

These slight structural age changes seem to have little or no effect on the functional capacity of the liver. This maintenance of function probably stems from two features. First, the liver has a very large functional reserve capacity. As much as 80 percent can be removed, and the remaining portion can maintain normal body operations when conditions are favorable. Second, the liver easily regenerates new cells when older ones are damaged or destroyed. This regenerative ability is unchanged by aging. Studies of age changes in the liver suggest that both the storage of vitamin C and glycogen and the removal of a few medications (e.g., acetanilide, diazepam) declines. Elimination of particulate material by Kupffer's cells may decline with aging. It is important to note that smoking significantly reduces toxin, waste, and drug elimination by the liver.

Abnormal Changes

Cirrhosis

A common and serious abnormal condition that often accompanies old age is the disease called cirrhosis. In this disease, the liver is converted into a lumpy scar-filled organ with greatly reduced functioning (Figure 10.6). Though many cases of cirrhosis occur among younger adults, this disease ranks among the top 10 causes of death among those over age 55.

Cirrhosis results from long-term repeated or continuous liver damage. Such damage among the elderly is most commonly caused when gallstones block large bile ducts. The resulting accumulation of bile in the liver puts pressure on liver cells and, together with chemicals in the trapped bile, damages them. Other causes include chronic alcohol consumption, hepatitis infections, and ingestion or inhalation of toxic substances such as volatile organic solvents in glue, cleaners, and paint thinners. Malnutrition, which is often associated with alcohol abuse, amplifies the effects of alcohol on the liver.

The development of cirrhosis occurs in basically the same way regardless of the cause. When liver cells are injured, the liver becomes inflamed and enlarged. Injured hepatocytes are not able to convert nutrients properly, resulting in accumulations of fat within the cells. Fibrous scar tissue then forms around the lobules. The presence of scar tissue inhibits the flow of blood and bile through the liver. With time, the flow of blood and bile is further restricted because the scar tissue shrinks, distorting and compressing blood vessels and bile passages. The liver attempts to compensate by forming new lobules. The growth of new lobules, along with compression by the scar tissue, gives the enlarged liver a lumpy appearance.

Since hepatocytes are injured, they are less able to perform their functions. Bilirubin from hemoglobin breakdown is left in a fat-soluble form called unconjugated bilirubin rather than being converted to the water-soluble conjugated form for excretion in bile. Inadequate amounts of bile are produced for emulsification and absorption. Since bile ducts are blocked, much of the bile cannot pass out of the liver to the hepatic duct. Therefore, digestion and absorption of fat and fat-soluble vitamins are reduced. Blood nutrient levels become unbalanced because of this and because the hepatocytes are less able to manufacture, convert, and store nutrients. All body cells become malnourished, as indicated by the onset of fatigue.

Blocked bile passages, together with the declining conversion of unconjugated bilirubin, result in accumulations of bilirubin. This gives the affected person a yellow or brown color, a condition called jaundice. Excessively high concentrations can eventually cause brain damage because unconjugated bilirubin accumulates in fatty myelin in the brain. In more advanced stages of cirrhosis, ammonia poses an even greater threat to the brain. Ammonia increases partly because of the dwindling conversion of ammonia to urea by hepatocytes. A second reason is that blocked blood flow causes blood from the intestines to flow through alternative routes, particularly veins in the esophagus. Thus, ammonia produced by intestinal bacteria is sent directly to the heart and from there to other organs, including the brain. Affected individuals show mental confusion, reduced muscle control, and even coma. This situation can eventually prove fatal.

The blockage of liver vessels causes other problems. Since blood cannot pass freely through the liver, it backs up into intestinal veins, causing them to swell and become varicose veins. When this happens in the rectum, hemorrhoids develop. When it happens in the esophagus, serious and even fatal bleeding can occur. As a further complication, extra fluids leak out of the stomach and intestinal capillaries into the surrounding abdominal cavity. This accumulation of fluids (ascites) causes abdominal swelling and imbalances in fluids in body cells in other regions.

Ascites worsens because reduced production of blood protein by injured hepatocytes allows more of the fluid to remain outside the capillaries. The reduction in blood proteins also causes edema and swelling in many parts of the body. The ascites and edema are amplified because injured hepatocytes do not remove enough steroid hormones from the blood (e.g., aldosterone, sex steroids), causing water retention by the kidneys. Edema causes a puffy appearance and discomfort, and in the lungs it significantly reduces respiratory functioning.

Many other problems result from cirrhosis. The more serious ones include bleeding because of reduced production of clotting materials, anemia because of poor hemoglobin breakdown and blood backing up into the spleen, weak bones because of reduced vitamin D activation, and reduced sexual functioning from abnormal hormone levels.

Many cases of cirrhosis are preventable. Individuals with blocked large bile ducts can usually have the blockages removed. This is especially true among the elderly, in whom the blocked ducts usually result from gallstones. Cirrhosis from chronic alcohol consumption (the other common cause of cirrhosis) can be prevented by avoiding or reducing the consumption of alcoholic beverages. Excessive alcohol consumption is a serious problem because many elderly people suffer from loneliness, depression, boredom, and anxiety. Staying active and receiving social and emotional support can help reduce the incidence of alcohol abuse, and good nutrition reduces the effects of alcohol on the liver. Hepatitis, another cause of cirrhosis, can be prevented by using good hygiene; avoiding contact with affected individuals, especially their feces, blood, and body fluids; and being immunized. Avoiding exposure to toxic materials can prevent other cases of cirrhosis.

Treatment of those with cirrhosis involves avoiding further liver injury by avoiding causative factors. If the cirrhosis is not very advanced, some liver regeneration and improvement in liver function can occur spontaneously. Advanced cirrhosis is essentially irreversible. Treatment at all stages includes minimizing the effects of complications from this disease.

Cancer

Most cases of cancer in the liver develop when cancer cells move through the hepatic portal system to the liver from other parts of the digestive system or the spleen. Movement of cancer from one location to another is called metastasis, and a cancer that metastasizes is called metastatic cancer. Metastatic cancer of the liver is often widespread and is of diverse types. It may reduce many liver functions and can cause several of the problems associated with cirrhosis.

Treatments for metastatic liver cancer, including surgery, radiation therapy, and chemotherapy, do little more than slow the progress of this fatal disease. Essentially all cases are fatal within 5 years.