1. Copyright 2007 by Saunders/Elsevier. All rights reserved. Chapter 18: Digestive System: Glands Color Textbook of Histology, 3rd ed. Gartner & Hiatt Copyright 2007 by Saunders/Elsevier. All rights reserved.

2. Salivary Glands Extramural glands of the digestive system include the salivary glands, pancreas, and liver. The secretory products of these glands assist in the digestive process and are delivered to the lumen of the alimentary tract by a system of ducts. By producing saliva, the salivary glands facilitate the process of tasting food, initiate its digestion, and permit its swallowing. These glands also protect the body by secreting the antibacterial agents lysozyme and lactoferrin as well as the secretory immunoglobulin IgA. The major salivary glands are the paired parotid, submandibular, and sublingual glands. The secretory portions of salivary glands are composed of serous and/or mucous secretory cells arranged in acini (alveoli) or tubules that are couched by myoepithelial cells, wheras their ducts are highly branched and range from very small intercalated ducts to very large principal (terminal) ducts. Although physically the largest of the salivary glands, the parotid gland produces only about 30% of the total salivary output; the saliva it produces is serous. The submandibular gland produces 60% of the total salivary output; although it manufactures a mixed saliva, the major portion is serous. The sublingual gland is very small, is composed mostly of mucous acini with serous demilunes, and produces a mixed saliva. For more information see Salivary Glands section in Chapter 18 of Gartner and Hiatt: Color Textbook of Histology, 3rd ed. Philadelphia, W.B. Saunders, 2007. Figure 18–1 Salivary gland acini, ducts, and cell types.

3. Copyright 2007 by Saunders/Elsevier. All rights reserved. Pancreas The pancreas produces exocrine and endocrine secretions. The endocrine components of the pancreas, islets of Langerhans, are scattered among the exocrine secretory acini. The Islets have five cell types, alpha cells (produce glucagon), beta cells (produce insulin), PP cells (produce pancreatic polypeptide), G cells (manufacture gastrin), and delta cells (manufacture somatostatin). The exocrine pancreas is composed of acini whose lumen is occupied by centroacinar cells, the beginning of the duct system of the pancreas. The acinar cells manufacture, store, and release digestive enzymes: pancreatic amylase, pancreatic lipase, ribonuclease, deoxyribonuclease, and proenzymes chymotrypsinogen, procarboxypeptidase, elastase, and. They also manufacture trypsin inhibitor, which protects the cell from intracellular activation of trypsin. Release of the pancreatic enzymes is effected by the hormone cholecystokinin (pancreozymin) manufactured by DNES cells of the small intestine as well as by acetylcholine released by postganglionic parasympathetic fibers. The centroacinar cells manufacture a bicarbonate-rich buffer, whose release is effected by the hormone secretin, produced by DNES cells of the small intestine and possibly in concert with acetylcholine. Thus the enzyme-rich and enzyme-poor secretions are regulated separately, and the two secretions may be released at different times or concomitantly. For more information see Pancreas section in Chapter 18 of Gartner and Hiatt: Color Textbook of Histology, 3rd ed. Philadelphia, W.B. Saunders, 2007. Figure 18–5 The pancreas with secretory acini, their cell types, and the endocrine islets of Langerhans.

4. Copyright 2007 by Saunders/Elsevier. All rights reserved. Liver The liver, similar to the pancreas, has both endocrine and exocrine functions, although, the same cell, the hepatocyte, is responsible for the formation of its exocrine secretion, bile, and its endocrine products. Hepatocytes also detoxify toxins and excrete them in bile. The liver’s connective tissue capsule, Glisson’s capsule, is loosely attached except at the porta hepatis, where it enters the liver, forming a conduit for the blood and lymph vessels and bile ducts. The liver is unusual, in that its connective tissue elements are sparse; thus, the bulk of the liver is composed of uniform parenchymal cells, the hepatocytes. The liver has a dual blood supply, receiving oxygenated blood from the hepatic arteries (25%) and nutrient-rich blood via the portal vein (75%). Both vessels enter the liver at the porta hepatis. Blood leaves the liver at the posterior aspect of the organ through the hepatic veins. Bile leaves the liver at the porta hepatis, by way of the hepatic ducts, to be delivered to the gallbladder for concentration and storage. Hepatocytes form hexagon-shaped classical lobules whose boundaries in human liver can only be approximated. The region where three classical lobules join each other, is known as a portal area which houses slender branches of the hepatic artery, tributaries of the relatively large portal vein, interlobular bile ducts, and lymph vessels. Each lobule has a single central vein which receives blood from every sinusoid of that lobule. As the central vein leaves the lobule, it terminates in the sublobular vein which eventually drains into the hepatic vein. For more information see the Liver section in Chapter 18 of Gartner and Hiatt: Color Textbook of Histology, 3rd ed. Philadelphia, W.B. Saunders, 2007. Figure 18–9 Liver. A, Gross anatomy of the liver. B, Liver lobules displaying the portal areas and the central vein. C, Portion of the liver lobule displaying the portal area, liver plates, sinusoids, and bile canaliculi.

5. Copyright 2007 by Saunders/Elsevier. All rights reserved. Liver Lobules There are three basic conceptualizations of the liver lobule. The classical liver lobule was the first to be defined histologically because the connective tissue arrangement in the pig liver afforded an obvious rationale. In this concept, blood flows from the periphery to the center of the lobule into the central vein. Bile, manufactured by liver cells, enters into small intercellular spaces, bile canaliculi, located between hepatocytes and flows to the periphery of the lobule to the interlobular bile ducts of the portal areas. To be consistent with lobules of other exocrine glands, delivering bile into a central lumen, the portal lobule was described as the triangular region whose center is the portal area and whose periphery is bounded by imaginary straight lines connecting the three surrounding central veins. A third conceptualization, known as the hepatic acinus (acinus of Rappaport) is based on blood flow. It is viewed as three poorly defined, concentric regions of hepatic parenchyma surrounding a distributing artery in the center. The outermost layer, zone 3, extends as far as the central vein and is the most oxygen-poor of the three zones. The remaining region is equally divided into two zones (1 and 2); zone 1 is the richest in oxygen. For more information see Three concepts of Liver Lobules section in Chapter 18 of Gartner and Hiatt: Color Textbook of Histology, 3rd ed. Philadelphia, W.B. Saunders, 2007. Figure 18–11 The three types of lobules in the liver: classical lobule, portal lobule, and hepatic acinus.

6. Copyright 2007 by Saunders/Elsevier. All rights reserved. Hepatocyte The plasma membranes of hepatocytes are said to have two domains, lateral and sinusoidal. The lateral domains form elaborate, intercellular spaces, 1 to 2 μ m in diameter, bile canaliculi, that conduct bile between hepatocytes to the periphery of the classical lobules. The sinusoidal domains of hepatocyte plasma membranes also have microvilli, which project into the space of Disse. It has been calculated that these microvilli increase the surface area of the sinusoidal domain by a factor of 6, facilitating the exchange of material between the hepatocyte and the plasma in the perisinusoidal space. Hepatocytes have an abundance of free ribosomes, RER, and Golgi apparatus. Each cell houses several sets of Golgi apparatuses, located near bile canaliculi. Each cell contains as many as 2000 mitochondria. Cells in zone 3 of the liver acinus have nearly twice as many, but smaller, mitochondria as liver cells in zone 1 of the liver acinus. Liver cells also have many endosomes, lysosomes, and peroxisomes. Cells in zone 3 of the liver acinus have the richest endowment of SER which increases in the presence of certain drugs and toxins because detoxification occurs within the cisternae of this organelle. Hepatocytes contain varying amounts of inclusions in the form of lipid droplets and glycogen. For more information see Hepatocytes section in Chapter 18 of Gartner and Hiatt: Color Textbook of Histology, 3rd ed. Philadelphia, W.B. Saunders, 2007. Figure 18–14 A hepatocyte and its sinusoidal and lateral domains. ER, endoplasmic reticulum. (From Lentz TL: Cell Fine Structure: An Atlas of Drawings of Whole-Cell Structure. Philadelphia, WB Saunders, 1971.)

7. Copyright 2007 by Saunders/Elsevier. All rights reserved. Liver Histophysiology The liver may have as many as 100 different functions, most of which are performed by the hepatocytes. Hepatocytes metabolize the end products of absorption from the alimentary canal, store them as inclusion products, and release them in response to hormonal and nervous signals. Liver cells also detoxify drugs and toxins and transfer secretory IgA from the space of Disse into bile. In addition, Kupffer cells phagocytose blood-borne foreign particulate matter and defunct erythrocytes. Bile contains bile salts, bilirubin glucuronide (bile pigment), phospholipids, lecithin, cholesterol, plasma electrolytes, and IgA. It emulsifies fat, eliminates approximately 80% of the cholesterol synthesized by the liver, and excretes blood-borne waste products such as bilirubin. Hepatocytes remove chylomicrons from the space of Disse and degrade them into fatty acids and glycerol. Additional responsibilities of the liver include the maintenance of normal blood glucose levels, deamination of amino acids and forming urea, as well as the synthesis of many blood proteins. Vitamin A is stored in the greatest amount in the liver, but vitamins D and B 12 are also present in substantial quantities. Drugs, such as barbiturates and antibiotics, and toxins are inactivated by microsomal mixed-function oxidases in hepatocytes. These drugs and toxins are usually inactivated in the cisterna of the SER by methylation, conjugation, or oxidation. Occasionally, detoxification occurs in peroxisomes rather than in the SER. Hepatocytes complex IgA with secretory component and release the secretory IgA into the bile canaliculi. Kupffer cells recognize and endocytose blood-borne microorganisms and also remove cellular debris and defunct erythrocytes from the blood. For more information see Histophysiology of the Liver section in Chapter 18 of Gartner and Hiatt: Color Textbook of Histology, 3rd ed. Philadelphia, W.B. Saunders, 2007. Figure 18–18 Hepatocyte function. SER, smooth endoplasmic epithelium. A, Protein synthesis and carbohydrate storage. B, Secretion of bile acids and bilirubin.