Digestive System-2

Other organs that are part of the digestive system include the liver, gall bladder and pancreas.

The liver is the largest gland in the body; it is multifunctional. To understand the function of the liver it is necessary to understand the blood supply to the liver. It is supplied by the hepatic artery in the typical manner but it is the only digestive organ drained by the inferior vena cava. Other digestive organs such as the small intestine, parts of the large intestine, stomach and pancreas are drained by the hepatic portal system which takes the blood directly to the liver. Thus, the liver receives oxygen poor, nutrient rich blood from the hepatic portal system and oxygen rich blood from the hepatic artery.

General organization. Structurally the liver is divided into lobules by loose connective tissue septae. These septae are more prominent in some domestic animals than in others; the pig has the most prominent septae and they are readily apparent grossly. For a long time the lobule as defined by these septae was thought to be the basic functional unit of the liver but now it seems that another unit, i.e., the hepatic acinus, might better represent the functional unit of the liver. Both the hepatic lobule and the hepatic acinus will be described but first the basic histology of the liver will be described.

At low magnification the liver looks relatively homogeneous and on first examination little organization can be discerned. A closer look reveals the presence of "lobules" or groups of hepatocytes arranged around a blood vessel, the central vein, and defined by loose connective tissue in which the portal canals are found. This type of organization is most easily seen in the pig liver.

Hepatocytes are one of the primary functional cells of the liver. They are located in flat irregular plates that are arranged radially like the spokes of a wheel around a branch of the hepatic vein, called the central vein or central venule since it really has the structure of a venule.

Portal canal: Three structures are found gouped together in the loose connective tissue surrounding the plates of hepatocytes. These include branches of the hepatic artery, the hepatic portal vein (venule) and the intralobular bile ductule. This group of three structures has been called a portal triad but now is called a portal canal.

Portal canal:

branch of the hepatic artery
branch of the hepatic portal vein (venule)
section of an intralobular bile ductule

Micrographs of pig liver (Lab slide 61)
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Arrows indicate the borders of a lobule;
CV=central vein; PC=portal canal.
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Sinusoids are larger than conventional capillaries and less regular in shape. They are lined by thin endothelial cells (E). Also residing on the sinusoidal walls are macrophages called Kupffer cells (K). These are phagocytic cells that remove particulate material and old red blood cells from circulation. Kupffer cells are members of the mononuclear phagocyte system

Hepatocytes are arranged in rows that radiate out from the central vein. These rows are one cell wide and are surrounded by sinusoidal capillaries or sinusoids. This arrangement ensures that each hepatocyte is in very close contact with blood flowing through the sinusoids, i.e. bathed in blood.

The endothelial cells lining sinusoids are fenestrated and in most species lack a basal lamina. Gaps are also present between the endothelial cells. Taken together these two properties make the sinusoids extremely leaky and allow for the extremely close contact between the blood and the surface of hepatocytes. Many materials in the blood, except for whole blood cells, can pass between the spaces in the sinusoidal lining.

Although sinudoidal endothelial cells lie very close to hepatocytes, they do not actually make contact. A narrow space is present between the surface of the hepatocyte and the surface of the endothelial cell. This is called the space of Disse; it is filled with numerous microvilli from the hepatocytes. As in other areas of the body, these structures serve to increase the surface area of the cell membrane that comes in contact with the blood facilitating exchange of molecules between hepatocytes and the blood.

What is the basic functional unit of the liver?

Hepatic lobule: The hepatic lobule is defined as having a central vein (CV) at its center with its edges defined by portal canals (PC). This model only takes into consideration the flow of blood in one direction, i.e., from the branch of the hepatic artery located in the portal canal toward the central vein. Yet, in the liver, blood actually flows from branches of the hepatic artery in several directions. Thus, the hepatic lobule does not define a "functional unit" of the liver very well.

Hepatic acinus: More recent terminology identifies the hepatic acinus as the "functional unit" of the liver. This definition recognizes both the real pattern of blood flow in the liver and the role of hepatocytes as secretory cells, secreting bile.

The hepatic acinus has three zones. Hepatocytes in Zone 1 are the first to receive blood and it is high in oxygen. Hepatocytes in Zone 2 are the second cells to receive blood and it is lower in oxygen. Hepatocytes in Zone 3 are the last to receive blood from a branch of the hepatic artery and it is lowest in oxygen. Thus, the cells with the highest metabolic potential are found in Zone 1 and those with the least are found in Zone 3. Importantly, the cells in Zone 3 are the most susceptible to ischemic conditions due to the already low level of oxygen that reaches them through the blood.

Secretion of bile in the liver

Bile is produced and secreted by hepatocytes into a special "duct" called a bile canaliculus. This "duct" is actually just a space formed between two hepatocytes that is separated from the connective tissue space around the hepatocytes by the presence of tight junctions. The bile canaliculi empty into branches of the bile ductules which eventually empty into the hepatic duct that carries the bile out of the liver to the gall bladder for concentration and storage. In the duct system, bile flows in the direction opposite to the flow of blood in the sinusoids.

Pig liver (Lab slide 61). HPV = hepatic portal vein; HA = hepatic artery; BD= bile ductule. Note that bile flows in the direction of the arrows, from its production by hepatocytes through the bile canaliculi toward the bile ductule.

The gall bladder receives bile from the liver. Bile is composed of bile salts that emulsify fats forming water-soluble complexes with lipids (micelles) to facilitate the absorption of fat. Bile salts in the small intestine also activates lipases in the intestine.

Gall bladder structure. The gall bladder is a sac that is lined with a simple columnar epithelium and has a tunica muscularis containing smooth muscle that is innervated by both the parasympathetic and sympathetic branches of the autonomic nervous system.

Tunics (layers) of the Gall Bladder

Tunica mucosa: When the gall bladder is empty, this layer is extremely folded. When full, this layer is smoother but still has some short folds.
- lamina epithelialis: composed of simple columnar epithelial cells with numerous microvilli on their luminal surfaces and connected by tight junctions near luminal surfaces.
- lamina propria: composed of loose connective tissue rich in reticular and elastic fibers to support the large shape changes that occur in the lamina epithelialisl; lamina propria may contain simple tubuloalveolar glands especially in ruminants. May be mucous or serous depending on species.
- lamina muscularis mucosae: not present
Tunica submucosa: present and typical
Tunica muscularis: contains much smooth muscle, poorly organized
Tunica serosa: present and typical

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Micrographs of dog gall bladder (Lab slide 63)

The pancreas contains both exocrine and endocrine components that secrete digestive enzymes and peptide hormones respectively. These two components are very different structurally and functionally but are intermingled within the gland. However, the organization of the exocrine part into acini make it fairly easy to recognize in histological sections as does the organization of the endocrine part around areas of high vascularity.

The exocrine pancreas. The exocrine portion of the pancreas is a compound acinar gland. It has many small lobules, each of which is surrounded by connective tissue septa through which run blood vessels, nerves, lymphatics, and interlobular ducts. Exocrine secretion by the pancreas is controlled by hormones and nerves. When the hormone, secretin, is released from neuroendocrine cells in the duodenum of the small intestine, the pancreas secretion is watery and rich in bicarbonate. This "basic" secretion helps to neutralize the acidic chyme as it comes into the small intestine. In addition, when cholecystokinin-pancreozymin (CCK) is released by neuroendocrine cells in the duodenum the pancreas secretes a product rich in enzymes that breakdown proteins, carbohydrates, lipids and nucleic acids in the lumen of the small intestine. Gastrin which is secreted by pyloric neuroendocrine cells also results in a pancreatic secretion rich in digestive enzymes. Two of the digestive enzymes secreted by the pancreas are trypsin and chymotrypsin; they are secreted as non-active, pro- or zymogen forms and are subsequently activated by enterokinase in the lumen of the duodenum to avoid digestion of the pancreatic acinar cells.

A compound acinar gland.

Acini: The secretory cells of the pancreas are arranged around a small lumen. The pancreatic acinar cells produce the digestive enzymes in the typical pattern of protein synthesis. However these cells are highly active in protein synthesis for export and this high activity is reflected in their bizonal staining properties with the typical dyes used for histology, i.e., hematoxylin and eosin. The basal region of these secretory cells usually stains intensely with hematoxylin reflecting the presence of large amounts of endoplasmic reticulum where the protein is being synthesized on ribosomes. These proteins move from the rough endoplasmic reticulum to the Golgi apparatus where they are glycosylated, then from the Golgi as secretory granules. In these granules the enzymes are found in an inactive or zymogen form. They are activated after release in to the duct system. The presence of numerous zymogen granules containing high concentrations of protein is reflected in the intense eosin staining in the apical region of the secretory cells. These granules are most abundant during fasting or between meals and least abundant after a meal has been ingested.
Ducts: The secretory product of the acinar cells is carried out of the pancreas by a duct system as in other exocrine glands.

The first part of the duct system is called the intercalated duct or intralobular duct. It is lined with cuboidal epithelial cells that secrete bicarbonate ion into the secretory product. This duct actually extends into the acinar lumen, where its walls consist of the pale staining centroacinar cells .

intercalated ducts have very little connective tissue around them but they lead into larger interlobular ducts which lie within more prominent connective tissue septa. Interlobular ducts are lined with a low columnar epithelium that may contain goblet cells. Interlobular ducts empty into the main pancreatic ducts that exit the pancreas.

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Micrograph of rabbit pancreas (Lab slide U). C=center of acinus.
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Micrograph of rabbit pancreas (Lab slide U). C=center of acinus. Note pale-stained centroacinar cell that forms the beginning of the lining of the intercalated or interlobular duct.

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Micrograph of rabbit pancreas (Lab slide U). Note the smaller intralobular duct as compared with the much larger interlobular duct.

The cells of the endocrine portion of the pancreas are arranged either in round-to-oval shaped areas rich in blood vessels known as the islets of Langerhans or they may be scattered throughout the exocrine portions of the pancreas near the acini or ducts. There are several different types of cells in the islet or other regions, each secreting a different peptide hormone. It is not possible to distinguish among these cells with routine hematoxylin and eosin stain used for histological preparations. Immunocytochemistry is necessary to identify which cells are secreting a particular peptide. This is done by staining with an antibody made to the specific peptide that is combined with a label that can be visualized at the light microscopic level such as immunoperoxidase.

Examples of peptide hormones secreted by the endocrine pancreas:

insulin - increases uptake of glucose by most cells; reduces blood level
glucagon - decreases uptake of glucose; increases blood level
somatostatin - many effects of gastrointestinal function; may inhibit insulin and glucagon secretion
vasoactive intestinal peptide
pancreatic polypeptide
motilin, serotonin, substance P

Micrograph of rabbit pancreas (Lab slide U) showing a typical islet of Langerhans, the endocrine part of the pancreas.