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CHAPTER 14. Pancreas, Liver, And Gallbladder

The microscopic study of animal tissues and cells

Plate 14-1. The Pancreas 
Plate 14-2. The Liver 
Plate 14-3. The Gallbladder

We now turn to three organs-actually, huge glands – that are intimately associated with the proper functioning of the digestive tract: the pancreas, liver, and gallbladder.

The pancreas, located near the duodenum, does double duty as an endocrine and an exocrine organ. The endocrine portion, called the Islets of Langerhans, contains cells that secrete the hormones Insulin and Glucagon. The exocrine pancreas, described in this chapter, is a complex gland that contains many secretory units called acini arranged around a system of ducts. The ducts eventually combine to form the large pancreatic duct that carries pancreatic juice, a mixture of sodium bicarbonate and digestive enzymes, to the lumen of the duodenum of the small intestine. The microscopic anatomy of the pancreas is straightforward and needs little elaboration in this overview. (Chapter 1 provides a description of the functional unit of the exocrine pancreas, the pancreatic acinar cell.)

The gallbladder, a saclike structure appended to the liver, concentrates and stores Bile for use by the small intestine in fat digestion. The microanatomy of the gallbladder, like that of the pancreas, is straightforward (see Plate 14-3).

The microscopic anatomy of the liver, however, unlike that of the pancreas and gallbladder, is difficult to understand. To do so requires an understanding of the liver Lobule, a collection of efficiently placed vessels and cells that allows the liver to function as an extremely effective filter for the blood.

Thinking of the liver as a massive cross-flow filter helps in understanding its organization. The blood that leaves the digestive tract contains newly acquired macromolecules of all kinds. Were this blood to pass on to the rest of the body as is, individuals would become quite ill in short order, as there are many noxious substances that need to be treated before coming into contact with cells and tissues. The liver, then, is a sort of treatment plant placed in the path of the circulatory system between the gut and the rest of the body. The liver receives blood from the Portal Vein, a large vessel that drains the alimentary canal. The blood is guided through the liver by a series of very leaky capillaries called sinusoids, which are, in turn, in intimate contact with the cells of the liver itself, the hepatocytes. It is the hepatocytes that contain the elaborate enzymatic machinery that detoxifies noxious substances, packages Glucose into Glycogen, breaks down Hemoglobin from dead red blood cells, and makes Bile.

The liver has another, completely different blood supply-oxygenated blood, fresh from The heart and lungs, that carries essential nutrients and gases to the hepatocytes. This blood comes into the liver via the Hepatic Artery. After the Portal Vein and the hepatic aretery enter the liver, they branch many times to form smaller and smaller vessels that supply the lobules of the liver. At this level the microanatomy of the liver becomes complex and difficlut to understand.

The Lobule is best illustrated diagramatically. Figure 14-1 shows one segment of a Lobule that contains all of its major element. Three of these elements — the Portal Vein, the Hepatic Artery, and the Bile duct — are grouped together to form a Portal Triad. An ideal liver Lobule, seldom seen in any given histologic section, consists of a group of portal triads arranged in circular fashion around a single Central Vein. Blood enters the Lobule peripherally at the Portal Triad, flows centrally through the leaky sinusoids between rows of hepatocytes, and is collected by the Central Vein. The Central Vein, which carries blood away from the Lobule, connects with larger vessels that carry blood out of the liver and back into the general circulation. Materials are exchanged quite freely between the blood in the sinusoids and the hepatocytes. In addition, many macrophages, called Kupffer Cells in the liver, are present near the walls of the sinusoids, where they police the area for unwanted particulate matter (including dead red blood cells).

Each Lobule, then, positions hepatocytes and incoming blood in an ideal spatial array so that the hepatocytes can “treat” the blood before it is returned to the general circulation. Bile, made by hepatocytes from the breakdown of Hemoglobinand other materials, flows from the hepatocytes into tiny channels between them called Bile Canaliculi. These Bile Canaliculi are not distinct vessels with walls of their own, but are channels that are lined by the cell membranes of adjacent hepatocytes. The Bile Canaliculi carry the Bile outward from hepatocytes to the Portal Triad, where the Canaliculi join a branch of the Bile duct. The Bile duct caries Bile to the gallbladder, where it is stored and eventually released into the lumen of the small intestine.

The pancreas, a 9-in.-long digestive gland, is located next to the duodenum. Actually two glands in one, the pancreas has an endocrine portion that secretes hormones (Insulin and Glucagon) and an exocrine portion that secretes digestive enzymes. This plate will describe the exocrine pancreas.

The exocrine pancreas secretes copious amounts (1200 ml/day) of a watery substance called pancreatic juice, which is a mixture of sodium bicarbonate and digestive enzymes that travels through a system of pancreatic ducts and is released directly into the lumen of the duodenum. The sodium bicarbonate buffers the acidic Chyme that enters the duodenum from the stomach; the digestive enzymes – trypsm, Amylase, and Lipase – break down the proteins, starches, and fats delivered to the duodenum from the stomach.

Figures A and B at right are a matched pair of light and electron micrographs of serial sections taken through the exocrine pancreas of the squirrel monkey. The histologic organization of the pancreas – especially the interrelationship of the secretory acini to the ducts-is difficult to visualize by light microscopy alone. Repeated comparison of the light and electron images at right will simplify that task considerably.

The pancreas contains thousands of acini. Each Acinus is a near-spherical secretory unit-a ball of pyramid – shaped secretory cells (also called acinar cells) dedicated to the elaboration and release of digestive enzymes. The Nucleus (N) of the acinar cell is located at the base of the cell. The secretory products are tightly packaged into dark-staining zymogen granules (Z) located at the apical pole of the cell. The zymogen granules are produced by an extremely well developed system of rough encloplasmic reticulum (RER) that fills the broad base of the acinar cell. Under the light microscope (Figure A), the nuclei and zymogen granules are clearly visible; the Endoplasmic Reticulum, however, is recognizable only because of its intensely basophilic-staining characteristics, which are not readily apparent in a black-and-white photograph.

In the electron micrograph, however, all of the components that are difficult to resolve by light microscopy are evident (Figure B). The rough Endoplasmic Reticulum (RER) appears as a series of closely apposed parallel Cisternae. Interspersed among the Cisternae of the rough Endoplasmic Reticulum are many Mitochondria that supply ATP to fuel the energy-consuming process of protein synthesis. The digestive enzymes elaborated by the pancreatic acinar cell, like all enzymes, are made of protein. The pancreatic acinar cell, then, may be thought of as a protein factory – a cell that manufactures protein for export. The protein molecules are assembled from their constituent amino acids upon messenger RNAattached to the ribosomes; the assembled protein molecules are collected within the Cisternae of the rough ER, ready for their transfer to the Golgi Apparatus and subsequent packaging into membrane-limited zymogen granules.

Other cells found within the secretory acini of the exocrine pancreas are centroacinar cells. They are easy to identify in electron micrographs but can be difficult to spot in the light microscope. The same Centroacinar Cell has been identified (*) in Figures A and B at right. Close inspection of the Centroacinar Cellshown in Figure B will reveal that it is identical to the epithelial cells (E) that line the Pancreatic Duct (D). The cells appear similar because the centroacinar cells are really duct cells that interconnect each secretory Acinus with a duct. Quite frequently, the plane of section will include part of an Acinus and its duct. The cells of each Acinus are arranged radially around a tiny lumen (L) – often not evident by light microscopy but readily visible by electron microscopy (Figure B). Because the lumen is coextensive with a duct, the centroacinar cells, as their name suggests, will appear in the center of each Acinus.



Plate 14-1
Plate 14-1. Figures A and B. Matched pair of light and electron micrographs of serial thick and thin sections through the pancreas of the monkey. A, pancreatic acinar cell; C, capillary; D, Pancreatic Duct; E, epithelium of duct; RER, rough Endoplasmic Reticulum; L, lumen of Acinus; N, Nucleus of acinar cell; V, vein (Fig. A only); Z, zymogen granules; *, Centroacinar Cell. Figure A, 1,800 X; Figure B, 2,800 X

The liver is a vital organ, essential for life. Its thousands of functions center mostly around taking up molecules and macromolecules from the blood, enzymatically modifying them, and eventually returning them to the bloodstream in different forms for distribution to and use by the rest of the body’s cells and tissues. After a meal high in sugar, for example, the liver extracts Glucose from the blood, converts it into Glycogen for storage, and maintains stores of Glycogen within its cells (the hepatocytes) for future use. When blood sugar levels fall below normal limits, however, liver cells convert Glycogen into Glucose and release it back into the bloodstream.

The liver enzymatically modifies the biochemistry of many substances, such as carbohydrates, proteins, Lipids, and steroids. In addition, the liver manufactures and secretes Bile – a fluid that, when released into the small intestine by the gallbladder, functions in fat digestion. In all of these processes save Bile secretion, interaction between liver cells and blood is crucial. The necessary interactions between liver cells and circulating blood provide the central principle around which the microanatomy of the liver is organized.

The Hepatocyte, or liver cell, is the individual unit of structure of the liver. As illustrated in Figure A, hepatocytes (H) are strung together in cords to form a simple Cuboidal Epithelium. Each cord of cells borders on a blood vessel, a Sinusoid, which is a large, leaky capillary with big holes in its endothelial lining that permit free passage of Plasma through its wall. The sinusoids (S) all converge on a Central Vein (CV) that receives blood from the sinusoids (arrows) and carries it away to large vessels that, in turn, return it to the heart.

The blood flowing from the sinusoids toward the central vein comes from two sources, the Portal Vein and the Hepatic Artery, illustrated in Figures B and C. The portal vein (PV) bears blood collected from the gut and the spleen and delivers it for filtering and processing to the hepatocytes via the sinusoids. The Hepatic Artery (HA) brings in fresh oxygenated blood to nourish the liver cells. Within the liver, the Portal Vein and the hepatic artery usually run side by side-along with the Bile duct-to form a structure called the Portal Triad. The liver, which in humans weighs 3 lbs, includes far more vessels than the single examples illustrated at right; there are thousands of central veins and many more thousands of portal triads. Central veins and portal triads are grouped into extremely efficient histologic units of structure called lobules. (See the overview for a diagram and a description of the liver Lobule.)

Blood flows through the liver rapidly. In humans, about 1 L of blood percolates through the liver sinusoids every minute. Given a total blood volume of 7 L, this flow rate is highly significant and underlines the importance of the liver to life.

Where, in this scheme, does the production and flow of Bile fit? Hepatocytes make Bile from Bile salts that are by-products of Hemoglobin catabolism. Hepatocytes release Bile into tiny channels, called Bile Canaliculi (*) (Figure A), that are spaces between each Hepatocyte and its neighbor. Bile flows from the hepatocytes outward toward the Bile ducts that are located at the periphery of the liver Lobulein the Portal Triad (see Figures B and C). The Bile ducts, in turn, carry the Bile to the gallbladder, which stores Bile and releases it into the lumen of the small intestine.

Plate 14-2
Plate 14-2. Figure A. Light micrograph of portion of liver Lobule showing radial organization of hepatocytes and sinusoids around the central vein. CV, Central Vein; H, Hepatocyte; S, Sinusoid; arrows, points of entry of sinusoids into Central Vein; *, Bile canaliculus, 300 X

Figures B and C. Matched pair of light and electron micrographs of serial sections taken through Portal Triad of monkey liver Lobule. BID, Bile duct; H, Hepatocyte; HA, Hepatic Artery; PV, Portal Vein; S, Sinusoid. Figure B, 600 X; Figure C, 1,000 X

The gallbladder is a pear-shaped sac attached to the liver. Its primary function is to concentrate and store the Bile produced by the hepatocytes of the liver. Under appropriate conditions of stimulation, the gallbladder releases its contents into the small intestine. There, Bile emulsifies fats, reducing them to micelles of triglyceride suitable for uptake by the columnar absorptive cells of the intestinal Mucosa.

The relationship between the function of the gallbladder and its microanatomic structure is evident in Figures A and B at right, a matched pair of light and electron micrographs of serial thick and thin sections through the gallbladder of the squirrel monkey. The wall of the gallbladder contains a Mucosa (MUC), a muscularis externa (ME), and an adventifia (AD). There is no Submucosa. The Mucosaconsists of a simple columnar epithelium (E) that lies atop a well-developed lamina propria (LP) made of loose connective tissue. The Muscularis Externa, not nearly as powerful as that of the intestine, consists of Smooth Muscle fibers set in many orientations – some circular, some longitudinal, most oblique. The Muscularis Externa is surrounded by an envelope of connective tissue, the Adventitia.

The epithelial cells that line the Mucosa are all alike and are well suited to perform their major function-concentrating Bile received from the liver. In many respects, the epithelial cells lining the gallbladder resemble the columnar absorptive cells of the small intestine; they possess a brush border consisting of Microvilli (arrow) and they lack the extensive system of rough endoplasmic reticulurn and Golgi Apparatus generally associated with cells actively engaged in the synthesis of protein for export.

The gallbladder, capable of concentrating Bile from 3 to 11 times, does so by removing water. From the level of the Nucleus to the Basement Membrane(arrowhead), the Plasma membrane that lines the lateral cell surface is thrown into a prominent and highly convoluted series of lateral infoldings (*). In addition, that same cell surface has, built into its structure, ATP – dependent transport enzymes that pump sodium chloride against an osmotic gradient. When the gallbladder starts to concentrate Bile, which it does largely by the process of water resorption, the epithelial cells pump large quantities of sodium chloride into the intercellular spaces between the epithelial cells, creating an osmotic gradient that pulls water out of the Bile and into the intercellular spaces. The intercellular spaces greatly distend, as is readily apparent in electron micrographs taken of gallbladders active in water resorption. Water then passes from the intercellular spaces into the Lamina Propria and enters the bloodstream through the many capillaries (C) that course through the Lamina Propria. This elaborate biochemical process requires energy, which is supplied in the form of ATP made by Mitochondria. Hence, the epithelial cells of the gallbladder contain many Mitochondria (M), as seen in Figure B.

Once the Bile has been concentrated, it is ready for transport into the lumen of the duodenum. When a person eats a fatty meal, which requires Bile for its emulsification, the intestinal Mucosa releases a hormone, Cholecystokinin, into the bloodstream. When Cholecystokinin reaches the gallbladder, it stimulates the Smooth Muscle fibers (S) of the Muscularis Externa to contract. (For this reason, patients with gallstones are advised to avoid eating fatty meals.) Muscular contraction forces the concentrated Bile out of the gallbladder, through the common Bile duct, and into the duodenum. In humans, from 0.5 L to 1 L of Bileflows from the gallbladder into the duodenum every day.


Figure 14-3
Figure 14-3. Figures A and B. Matched pair of light and electron micrographs through the wall of the gallbladder of the monkey. AD, Adventitia; C, capillary; E, epithelium; F, Fibroblast; L, lumen of gallbladder; LP, Lamina Propria; M, mitochondrion (Figure B); ME, muscularis externa; MUC, access; S, Smooth Muscle Fiber; *, lateral infoldings; arrow, brush border; arrowhead, location of Basement Membrane. Figure A, 1,600 X; Figure B, 2,000 X