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Although the liver is a discrete organ, it performs many different interrelating functions. The critical interrelated functions of the liver become especially evident when abnormalities of the liver occur. This chapter summarizes some of the major functions of the liver, including the following: (1) filtration and storage of blood; (2) metabolism of carbohydrates, proteins, fats, hormones, and foreign chemicals; (3) formation of bile; (4) storage of vitamins and iron; and (5) formation of coagulation factors.
Physiologic Anatomy of the Liver
The liver is the largest organ in the body, contributing about 2% of the total body weight, or about 1.5 kilograms (3.3 pounds) in the average adult human. The basic functional unit of the liver is the liver lobule , which is a cylindric structure several millimeters in length and 0.8 to 2 millimeters in diameter. The human liver contains 50,000 to 100,000 individual lobules.
The liver lobule, shown in cut-away format in Figure 71-1 , is constructed around a central vein that empties into the hepatic veins and then into the vena cava. The lobule is composed principally of many liver cellular plates (two of which are shown in Figure 71-1 ) that radiate from the central vein like spokes in a wheel. Each hepatic plate is usually two cells thick, and between the adjacent cells lie small bile canaliculi that empty into bile ducts in the fibrous septa separating the adjacent liver lobules.
In the septa are small portal venules that receive their blood mainly from the venous outflow of the gastrointestinal tract via the portal vein. From these venules blood flows into flat, branching hepatic sinusoids that lie between the hepatic plates and then into the central vein. Thus, the hepatic cells are exposed continuously to portal venous blood.
Hepatic arterioles are also present in the interlobular septa. These arterioles supply arterial blood to the septal tissues between the adjacent lobules, and many of the small arterioles also empty directly into the hepatic sinusoids, most frequently emptying into those located about one third the distance from the interlobular septa, as shown in Figure 71-1 .
In addition to the hepatic cells, the venous sinusoids are lined by two other cell types: (1) typical endothelial cells and (2) large Kupffer cells (also called reticuloendothelial cells ), which are resident macrophages that line the sinusoids and are capable of phagocytizing bacteria and other foreign matter in the hepatic sinus blood.
The endothelial lining of the sinusoids has extremely large pores, some of which are almost 1 micrometer in diameter. Beneath this lining, lying between the endothelial cells and the hepatic cells, are narrow tissue spaces called the spaces of Disse , also known as the perisinusoidal spaces . The millions of spaces of Disse connect with lymphatic vessels in the interlobular septa. Therefore, excess fluid in these spaces is removed through the lymphatics. Because of the large pores in the endothelium, substances in the plasma move freely into the spaces of Disse. Even large portions of the plasma proteins diffuse freely into these spaces.
Hepatic Vascular and Lymph Systems
The function of the hepatic vascular system is discussed in Chapter 15 in connection with the portal veins and can be summarized as follows.
Blood Flows Through the Liver From the Portal Vein and Hepatic Artery
The Liver Has High Blood Flow and Low Vascular Resistance
About 1050 ml/min of blood flow from the portal vein into the liver sinusoids, and an additional 300 ml/min flow into the sinusoids from the hepatic artery, with the total averaging about 1350 ml/min, which is 27% of the resting cardiac output.
The pressure in the portal vein leading into the liver averages about 9 mm Hg, and the pressure in the hepatic vein leading from the liver into the vena cava normally averages about 0 mm Hg. This small pressure difference, only 9 mm Hg, shows that the resistance to blood flow through the hepatic sinusoids is normally very low, especially when one considers that about 1350 ml/min of blood flow by this route.
Cirrhosis of the Liver Greatly Increases Resistance to Blood Flow
When liver parenchymal cells are destroyed, they are replaced with fibrous tissue that eventually contracts around the blood vessels, thereby greatly impeding the flow of portal blood through the liver. This disease process is known as cirrhosis of the liver . It results most commonly from chronic alcoholism or from excess fat accumulation in the liver and subsequent liver inflammation, a condition called nonalcoholic steatohepatitis, or NASH. A less severe form of fat accumulation and inflammation of the liver, nonalcoholic fatty liver disease (NAFLD), is the most common cause of liver disease in many industrialized countries, including the United States, and is usually associated with obesity and type 2 diabetes.
Cirrhosis can also follow ingestion of poisons such as carbon tetrachloride, viral diseases such as infectious hepatitis, obstruction of the bile ducts, and infectious processes in the bile ducts.
The portal system is also occasionally blocked by a large clot that develops in the portal vein or its major branches. When the portal system is suddenly blocked, the return of blood from the intestines and spleen through the liver portal blood flow system to the systemic circulation is impeded. This impedance results in portal hypertension, with the capillary pressure in the intestinal wall increasing to 15 to 20 mm Hg above normal. If the obstruction is not relieved, the patient may die within a few hours because of excessive loss of fluid from the capillaries into the lumens and walls of the intestines.
The Liver Functions as a Blood Reservoir
Because the liver is an expandable organ, large quantities of blood can be stored in its blood vessels. Its normal blood volume, including that in the hepatic veins and hepatic sinuses, is about 450 ml, or almost 10% of the body’s total blood volume. When high pressure in the right atrium causes backpressure in the liver, the liver expands, and 0.5 to 1 liter of extra blood is occasionally stored in the hepatic veins and sinuses. This storage of extra blood occurs especially in cases of cardiac failure with peripheral congestion, which is discussed in Chapter 22 . Thus, in effect, the liver is a large, expandable, venous organ capable of acting as a valuable blood reservoir in times of excess blood volume and capable of supplying extra blood in times of diminished blood volume.
The Liver Has Very High Lymph Flow
Because the pores in the hepatic sinusoids are very permeable compared with capillaries in other tissues, they allow ready passage of both fluid and proteins into the spaces of Disse. Therefore, the lymph draining from the liver usually has a protein concentration of about 6 g/dl, which is only slightly less than the protein concentration of plasma. In addition, the high permeability of the liver sinusoid epithelium allows large quantities of lymph to form. Therefore, about half of all the lymph formed in the body under resting conditions arises in the liver.
High Hepatic Vascular Pressures Can Cause Fluid Transudation Into the Abdominal Cavity From the Liver and Portal Capillaries—Ascites
When the pressure in the hepatic veins rises only 3 to 7 mm Hg above normal, excessive amounts of fluid begin to transude into the lymph and leak through the outer surface of the liver capsule directly into the abdominal cavity. This fluid is almost pure plasma, containing 80% to 90% as much protein as normal plasma. At vena caval pressures of 10 to 15 mm Hg, hepatic lymph flow increases to as much as 20 times normal, and the “sweating” from the surface of the liver can be so great that it causes large amounts of free fluid in the abdominal cavity, which is called ascites . Blockage of portal flow through the liver also causes high capillary pressures in the entire portal vascular system of the gastrointestinal tract, resulting in edema of the gut wall and transudation of fluid through the serosa of the gut into the abdominal cavity. This can also cause ascites.
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