ANATOMY 118/158  =  General Histology
Fall Quarter, 1998

GLANDS ASSOCIATED WITH THE DIGESTIVE TRACT:
LIVER, PANCREAS, AND SALIVARY GLANDS

Dr. Douglas Cooper
Last edited: 12/07/98

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OVERVIEW

The liver, pancreas and salivary glands are glands intimately associated with the anatomy and function of the digestive tract. The liver is not only the largest organ, other than skin, in the body (approximately 1.5 kilograms), but might also be said to have the most diverse roles of any organ in the body. Over 500 different functions are ascribed to the liver. Of its many critical roles, some are related to digestion and some are unrelated. For instance, the liver serves as an exocrine gland, secreting bile into the small intestine to help solubilize fats for digestion and absorption, but the liver also serves as an important storage organ and endocrine gland, secreting many important substances into the blood. The pancreas, too, has both exocrine and endocrine functions. It secretes a spectrum of digestive enzymes into the intestine to breakdown ingested material into smaller molecules for absorption, and it secretes hormones, such as insulin, into the blood. The salivary glands are more typical exocrine glands, secreting saliva into the oral cavity to lubricate and solubilize food, initiate digestion, and protect against microbes.

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LIVER


 Contents:
    Liver Objectives
    I.  Liver Introduction
    II.  Liver Anatomy
       A.  Capsule and internal connective tissue
       B.  Stroma
       C.  Gall bladder and biliary duct system
       D.  Blood supply
    III.  Functions Summarized
    IV. Clinical Correlations - Liver Regeneration
    V.  Liver Laboratory
   

LIVER OBJECTIVES

A. Describe the structure of the classical liver lobule, including the arrangement
      of hepatocytes, sinusoids, portal areas, and central vein.
B. Name the major structures found in the portal areas.
C. Describe the blood flow to the liver and lobule.
D. Describe the flow of bile from its origin at the hepatocyte to the intestine.
E. Describe the special features of liver sinusoids.
F. List the major hepatocyte organelles and a major function associated with each.
G. Describe the function and histological anatomy of the gallbladder.

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I. LIVER INTRODUCTION

The liver is a large, multi-lobed organ located at the top of the abdominal cavity immediately beneath the diaphragm. It serves as an interface between blood returning from the digestive tract (the portal venous system) and the rest of the bloodstream (via the hepatic venous system). Nutrients absorbed from the intestine and carried in the portal blood are processed and stored in the liver and then mobilized into the hepatic blood when needed by other organs. The liver also produces bile, an exocrine secretion passed through bile ducts into the gall bladder and so into the intestine. In addition, the liver plays a critical role in inactivating and eliminating many toxic substances absorbed from the intestine.

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II. LIVER ANATOMY

Liver anatomy is somewhat complex and unusual. Figures 16-11 and 16-12 (in Junquiera et al.) are good schematic diagrams that include most of the features discussed below. Keep them handy to help you understand the material below.

A. Capsule and internal connective tissue

A thin connective tissue capsule surrounds the liver. At one point the portal vein and hepatic artery enter and the lymphatics and bile ducts exit. These vessels and ducts are surrounded by a progressively thinner connective tissue sheath as they branch and penetrate throughout the liver stroma to individual portal spaces between each liver lobule. Only a thin reticular fiber network separates and supports each hepatocyte.

liver-piglobules.jpg (30721 bytes)

B. Stroma

The stroma of the liver is neatly packed with a basic architecture of polygonal columns, called liver lobules. In some animals (see figure above), but not humans, the connective tissue separating lobules is thick enough that they are easily distinguished by light microscopy. Portal spaces at the corners between lobules have more connective tissue surrounding portal triads composed of a portal venule bundled with a hepatic arteriole, and a bile duct. Small lymphatics and autonomic nerves also run through this space.

liver-triad.jpg (32797 bytes)

The human liver has three to six portal triads per liver lobule. The triads define the corners of the polygonal lobules, with the centers defined by a central vein. Radiating from the center to the lobule periphery are branching, anastamosing plates of hepatocytes, one or two cells thick, separated by capillaries, the liver sinusoids. This gives a spongelike architecture to the lobule. The sinusoids arise from terminal branches of the portal veins at the lobule periphery and terminate in the central vein. As the central vein progresses along the length of a lobule, it receives the inflow from more and more sinusoids and increases in diameter until joining a larger sublobular vein at the lobule base.

livlobul-schem.gif (162258 bytes)

 

liver-centvein.jpg (41041 bytes)

The liver sinusoids are unusual capillaries composed of a discontinuous layer of endothelial cells with large, irregular openings or fenestrations, about 100 nm in diameter. The basement membrane (basal lamina) under these endothelial cells is also incomplete. Between the sinusoids and the hepatocytes is a subendothelial space called the space of Disse. Microvilli from the hepatocytes protrude into this space. Blood plasma easily percolates through the sinusoidal fenestrations into the space of Disse and so makes intimate contact, facilitating exchange, with the hepatocyte.

liver-hi.jpg (53086 bytes)

On the lumenal surface of the endothelial cells, the sinusoids also contain scattered phagocytic Kuppfer cells. These are macrophages which ingest and degrade old erythrocytes and many kinds of debris in the blood. Breakdown of hemoglobin in these macrophages produces bilirubin, a yellowish, hydrophobic and somewhat toxic compound. Bilirubin is transported to the hepatocytes and there is modified to become more soluble and then excreted into the bile. When bilirubin excretion is impaired or production exceeds the liver's capacity to excrete it, it begins to accumulate in blood and peripheral tissues, causing jaundice.

lhepatocyte-schem.gif (102593 bytes)

Hepatocytes are large polyhedral cells 20-30 µm in diameter. They are technically epithelial cells, but very unusual in not sitting on a basement membrane and not being organized as a 2-dimensional sheet. Their cytoplasm is very rich in mitochondria, ribosomes, endoplasmic reticulum (both smooth and rough), Golgi complexes, peroxisomes, and lysosomes and appears eosinophic in H+E stained sections. The abundance of rough e.r. and Golgi reflects their active production of many important blood proteins, such as albumin and fibrinogen. The smooth e.r. carries out several important processes, including oxidation and conjugation required to detoxify various substances, and triglyceride and cholesterol metabolism prior to secretion. Many detoxified substances are excreted by way of the bile. Hepatocytes are also the body's main site for deamination of amino acids, producing urea which is transported into the blood and secreted by the kidneys.

The hepatocyte cytoplasm also contains granules of glycogen, a polysaccharide storage form of glucose, and lipid droplets, depots of triglycerides. Liver is the organ with primary responsibility for maintaining a constant blood glucose level. This is especially critical for brain function. Excess glucose is taken up and stored as glycogen. Glucose is produced by hydrolysis of glycogen, glycogenolysis, and by metabolism of amino acids or lipids, gluconeogenesis.

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C. Gall bladder and biliary duct system

Each hepatocyte is in contact with other hepatocytes and, via microvilli, with the wall of a sinusoid. Enclosed in each plane between adjacent hepatocytes is a tubular space called a bile canaliculus, which is the start of the bile duct system. Adjacent hepatocyte membranes are in close contact except for these little gaps, which are sealed by tight junctions. Thus, a canaliculus is a narrow sealed gap between the membranes of two hepatocytes. A few small microvilli protrude into the canaliculus from the hepatocytes. The canaliculi form an anastomosing tree draining toward bile ductules in the portal triads. The ductules are lined by simple cuboidal epithelium and merge to form the hepatic duct which, after joining the cystic duct, is called the common bile duct and conducts bile from the liver to the small intestine. The cystic duct is a branch of the hepatic duct which leads to the gall bladder, where excess bile is stored and concentrated. These ducts are lined by simple columnar epithelium.

bileduct.jpg (53881 bytes)

The gall bladder is a small pear-shaped organ attached to the underside of the liver. It, too, is lined by a simple columnar epithelium over a thin lamina propria and layer of circumferentially oriented smooth muscle, surrounded by connective tissue. The epithelial cells have microvilli on their apical surface and can absorb salt and water out of the stored bile to concentrate it. Dietary fats induce the release of cholecystokinin from specialized intestinal epithelial cells, and cholecystokinin triggers contraction of the gall bladder smooth muscle, so expelling bile into the intestine. Remarkably, the gall bladder can be removed, for instance when blocked with gall stones, with little effect on fat digestion and absorption.

liver-gallbl-hi.jpg (14134 bytes)

Bile is mostly composed of bile acids, lipids such as cholesterol, and bilirubin. The bile acids act as detergents, emulsifying lipids in the digestive tract and thus facilitating digestion by lipase and absorption. Bile acids are synthesized by the hepatocyte smooth e.r. by conjugation of cholic acid (derived from cholesterol) and amino acids, forming, for instance, glycocholic and taurocholic acids. Abnormal bile acid composition can form insoluble aggregates, gall stones, which can cause painful blockage of bile outflow.

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D. Blood supply

The liver blood supply is unusual in the sense that it derives from two sources, the hepatic artery (20%) and the portal vein (80%). The portal vein carries oxygen-poor, nutrient-rich blood from the intestine, pancreas, and spleen. It branches to send portal venules to the portal triads, which branch again sending smaller venules around the periphery of the lobule. From these arise smaller venules that empty into the sinusoids. Oxygen is supplied to liver cells by the hepatic artery, which carries oxygen-rich blood from the aorta. It branches to form the interlobular arteries, which branch to empty directly into the sinusoids, thus mixing oxygen-rich arterial and nutrient-rich portal venous blood around the hepatocytes. The sinusoids conduct the blood centrally, converging into the central vein. Central veins leave the lobules at their base as the sublobular veins, which converge to form the hepatic veins and empty into the inferior vena cava.

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III. LIVER FUNCTIONS SUMMARIZED

A. Blood Protein Synthesis
    Clotting proteins such as fibrinogen.
    Transport proteins such as retinol binding protein (carries vitamin A),
        lipoproteins (carry lipids), and transferrin (carries iron).
    Albumin

B. Bile Acid Synthesis

C. Maintenance Of Blood Glucose Levels
    Uptake and storage as glycogen lowers blood glucose levels.
    Glycogenolysis and gluconeogenesis raise blood glucose levels.

D. Phagocytosis and Detoxification
    Kuppfer cell digestion of aged erythrocytes and blood proteins,
        other particulates and pathogens.
    Primary site for oxidation, conjugation, metabolism of many drugs and toxins.
    Secretion of bilirubin and other waste products into bile.

E. Amino Acid Catabolism
    Deamination of amino acids produces urea, excreted by the kidneys.

F. Storage
    e.g. glycogen, lipids, vitamin A, iron

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IV. CLINICAL CORRELATIONS - Liver Regeneration

The liver has a remarkable capacity to regenerate when injured or partially removed. Although liver cell proliferation is normally very slow, loss of hepatic tissue causes a great increase in proliferation, which continues until the original liver mass is replaced. This is a great advantage for liver transplants. The architecture of the regenerated liver is at first very similar to the original, but repeated damage, for instance due to alcoholism, causes cirrhosis, a syndrome of progressive disorganization, accumulation of connective (scar) tissue, and loss of liver function.

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V. LIVER LABORATORY

OBJECTIVES

Be able to identify and describe the arrangement and function of the components of a liver lobule, its dual blood supply, and the drainage of bile from the lobule to the gall bladder. Also, understand the organization of the gall bladder: its epithelium, loose connective tissue, circumferential smooth muscle, adventitia, and duct system.

LABORATORY

A. Lobules - Identify liver lobules in slides #70 and #72. Observe the organization of plates of hepatocytes running radially around central veins. Study the portal triads and identify the component bile duct, hepatic artery, and portal vein. Bile canaliculi between hepatocytes are too small to be easily resolved at 40X.

B. Sinusoids with Kupffer cells - Slide #71 was prepared after injection of a rat with monastral blue dye to highlight phagocytic Kupffer cells which ingested this colloidal material. Identify the Kupffer cells in the sinusoids and compare them to the endothelial cells and hepatocytes.

C. Bile ducts and gall bladder - Slide #72 includes a large section of gall bladder. The simple columnar epithelial lining has a few folds and pockets, but is mostly flat. These cells secrete mucus which lubricates and helps protect the cells from the stored bile. Beneath the epithelium is a thin lamina propria with immune cells, then a thin layer of circumferential smooth muscle cells, and then an outer layer of loose adventitia or, in some places, serosa. Don't confuse large hepatic veins with gall bladder!

liver-vein-gallbl.jpg (44035 bytes)

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SALIVARY GLANDS

 Contents:
    Salivary Glands Objectives
    I.  Introduction
    II. Anatomy
       A.   Connective tissue capsule and major ducts
       B.  Serous acini and mucous tubules
       C.  Duct system
    III.  Functions Summarized
    IV. Clinical Correlations - Dental Caries, Sjogren's
    V.  Laboratory
   

OBJECTIVES

A. Describe the location and histological structure of the three major salivary glands.
B. Describe the functional and histological differences between serous and mucous
        cells.
C. Explain how different proteins secreted by salivary glands control oral bacteria.


I. SALIVARY GLANDS INTRODUCTION

Saliva is produced by small ("intrinsic") salivary glands scattered throughout the mouth and by three large, paired, ("extrinsic") salivary glands: the parotid, sublingual, and submaxillary glands. Each of these is composed of two basic types of cells: serous and mucous.

Serous cells are primarily responsible for producing a watery fluid rich in inorganic ions (calcium, phosphorus, sodium, potassium, chloride, etc.) and digestive enzymes. This mixture initiates solvation and digestion of food. Among the enzymes secreted are amylase, which hydrolyzes starch, and lysozyme, which hydrolyzes the walls of gram negative bacteria. Serous cells also secrete other defense proteins, including lactoferrin, which binds iron (a nutrient necessary for bacterial growth), and antibacterial peptides. The high concentration of inorganic ions secreted is important in keeping tooth minerals from dissolving. High levels of bicarbonate buffer acids ingested or produced by bacterial fermentation. Keeping the pH high is important for keeping the saliva supersaturated with calcium and phosphorus, preventing tooth demineralization and even driving remineralization to some extent.

Mucous cells produce mucus, a thicker fluid rich in mucin glycoproteins which help lubricate the oral cavity and ease swallowing.

Whereas the small scattered glands secrete almost continuously under local control, secretion from the large salivary glands is controlled by the autonomic nervous system. That's how the aromas wafting from the pizza parlor cause you to salivate. Total salivary secretion runs at a basal rate of about 1.0 ml/min, but is increased many fold during meals. Total daily flow is over a liter!

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II. SALIVARY GLAND ANATOMY

A.  Connective tissue capsule and major ducts

The large salivary glands are surrounded by a connective tissue capsule with septa that penetrate the body of the glands and divide them into lobules. Vessels and nerves enter the gland at the hilum and follow the septa as they progressively branch into the lobules. The parotid glands are by far the largest and are located subcutaneously on each side of the face just in front of the ear. For each a long duct, Stenson's duct, drains into the oral cavity opposite the second upper molar. The location of the other glands is more self-explanatory. The submaxillary (submandibular) glands lie on either side of the mouth between the maxilla (mandible) and the muscles forming the floor of the mouth. They drain by Wharton's ducts which open at the tip of the sublingual papilla next to the frenulum of the tongue. Deep under the tongue lie the sublingual glands on either side of the frenulum and these drain by major ducts which join the ducts of the submaxillary glands and by several smaller ducts that open individually.

submaxgross.jpg (36469 bytes)

B.  Serous acini and mucous tubules

saliv-schem.gif (91551 bytes)

Serous cells are typical polarized, secretory, epithelial cells arranged as wedges to form a sphere, called an acinus, around a central lumen. At one side a duct carries fluid out of the acinus and merges into a branching duct system such that many acini resemble a cluster of grapes attached to a branching stem. The broad base of pyramidal serous cells rests on a basement membrane surrounding each acinus. The apex of each serous cell has short microvilli facing into the acinar lumen. The lateral space between these cells is sealed by junctional complexes (tight junctions, adhering junctions, desmosomes, and gap junctions). Abundant rough e.r., Golgi, and protein-rich secretory vesicles (zymogen granules), give these cells a basophilic appearance by typical H+E staining.

Mucous cells are cuboidal to columnar epithelial cells arranged to form tubules with a central lumen. Their nucleus is oval and pressed toward the base of the cell by the abundant rough e.r., Golgi, and large secrtory vesicles. The mucus contents of the large secretory vesicles are not preserved by typical fixation and staining conditions, and the resultant empty spaces give the cells a pale, foamy appearance. Again, the base of mucous cells rests on a basement membrane, which ensheaths the tubule, and their apex faces the lumen.

The relative proportion of serous and mucous cells differ markedly in the major salivary glands. The parotid glands are primarily composed of serous cells forming a typical branched acinar gland structure.

The submaxillary (submandibular) glands are composed of a mixture of mucous cell tubules capped by serous cell acini and so are called tubuloacinar glands. The serous cells predominate and are easily distinguished from the mucous cells in a typical H+E stained section by their more basophilic cytoplasm and rounded nuclei.

Submax1.jpg (64108 bytes)

The sublingual glands are another tubuloacinar gland, but in this case mucous cells predominate. Acini are composed of both serous and mucous cells with the serous cells mostly displaced to the terminal portion of the acini as outpocketings. They appear as darkly staining crescents of cells (serous demilunes) around the ends of mucous tubules.

sublingual.jpg (49782 bytes)

In both serous acini and mucous tubules, myoepithelial cells lie scattered between the epithelial cells and the basement membrane. They are interconnected by gap junctions and desmosomes. Around serous acini, myoepithelial cells are highly branched and form an interconnected basket (hence sometimes called basket cells) surrounding the acinus. They are very thin and usually only their nuclei can be discerned in sections. Along mucous tubules, myoepithelial cells are elongated, spindle-shaped, arranged parallel to the long axis of the tubule, and very difficult to discern. The myoepithlelial cells contain the muscle contractile proteins, myosin and tropomyosin, and are innervated by parasympathetic nerves, which can stimulate them to contract, so helping to expel saliva.

The connective tissue of the salivary glands is rich in lymphocytes and plasma cells which secrete the immunoglobulin, IgA. This type of immunoglobulin is transported specifically through epithelial cells (transcytosis) into the lumen, and in this case is important for defense against oral pathogens.

C.  Duct system

The duct system in these glands starts with the acinar and tubular ends which empty into intercalated ducts lined by simple cuboidal epithelium.

saliv-intercduct2.jpg (36358 bytes)

These join to form intralobular ducts, also called striated ducts because infoldings of the basal membranes of their lining cells give the appearance of radial striations from the base to the nuclei of the cells.

striatedducthi.jpg (36330 bytes)

These ducts converge to join as interlobular ducts (or excretory ducts) in the connective tissue septa separating the gland lobules. The interlobular ducts are lined with stratified cuboidal epithelium becoming stratified columnar epithelium toward their distal ends. These ducts join to form the main duct of each gland, lined by stratified, non-keratininized, squamous epithelium, like the oral cavity into which they empty.

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III. SALIVARY GLAND FUNCTIONS SUMMARIZED

A. Lubrication
B. Solvation - aids digestion and taste
C. Digestion - particularly hydrolysis of starch by amylase
D. Defense - IgA, lysozyme, and lactoferrin secretion

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IV. CLINICAL CORRELATIONS - Dental Caries, Sjogren's syndrome

Saliva composition is a major factor influencing the bacterial flora of the mouth and the formation of dental caries and plaque. These are obviously topics central to your training that you will hear about many times, but a quick summary here seems appropriate. Saliva helps protect against tooth decay in several ways:

1. Saliva flow helps dilute and clear dietary sugars.
2. High pH (bicarbonate) buffers acids generated by bacterial fermentation.
3. Calcium and phosphorus supersaturation drives toward mineralization.
4. IgA from mucosal plasma cells is transcytosed into saliva.
5. Antimicrobial peptides and proteins, e.g. lysozyme and lactoferrin.

Given the above, its easy to understand why patients with impaired production of saliva are at greatly increased risk for tooth decay and other oral problems. Insufficient saliva production to the point of relative oral dryness is called xerostomia. One cause of this condition is Sjogren's syndrome, an autoimmune disease in which patients mount an immune attack against their own salivary and tear glands. Often their dentist is the first to suspect the disease, because of extensive and unexplained dental caries. More than 1 million people in the US, 80% female, suffer from Sjogren's syndrome. Other causes of xerostomia include radiation therapy of oral cancers, with resultant destruction of salivary gland epithelia, and some drugs, in particular anticholinergic drugs, but also some sedatives, anti-psychotics, and antihistamines. Salivary gland function also tends to decline with age, and the elderly are particularly susceptible to drug induced xerostomia.

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V. SALIVARY GLANDS LABORATORY

OBJECTIVES

Be able to identify and describe the arrangement and function of the mucous and serous secretory cells, the duct systems, and the major connective tissue cells. Be able to differentiate the submaxillary, parotid and sublingual glands.

LABORATORY

The large salivary glands are each surrounded by a connective tissue capsule with septa that penetrate the body of the glands and divide them into lobules. Vessels and nerves enter the gland at the hilum and follow the septa as they progressively branch into the lobules. The duct system in these glands starts at each serous acinus or mucous tubule end which empty into intercalated ducts lined by simple cuboidal epithelium. These join to form intralobular ducts, also called striated ducts because infoldings of the basal membranes of their lining cells give the appearance of radial striations from the base to the almost central nuclei. These ducts converge to join as interlobular ducts (or excretory ducts) in the connective tissue septa separating the gland lobules. The interlobular ducts are lined with stratified cuboidal epithelium becoming stratified columnar epithelium toward their distal ends. These ducts join to form the main duct of each gland, lined by stratified, non-keratininized, squamous epithelium, like the oral cavity into which they empty.

A. Submaxillary - Slides #51 and #52 are sections of sumaxillary gland and clearly demonstrate the two types of salivary secretory cells. This gland is primarily composed of serous acini with fewer scattered mucous tubules, some showing serous demilune caps. Note the basal nuclei and granular appearance of the cytoplasm due to the stored secretory granules. The serous cell cytoplasm is somewhat basophilic due to abundant rough e.r., Golgi, and the protein-rich secretory vesicles (zymogen granules), whereas the mucous cell cytoplasm has a pale, foamy appearance, because mucin in the large secretory vesicles is not preserved by typical fixation and staining conditions. Try to find each type of duct from the smallest simple cuboidal intercalated ducts draining the acini into the intralobular striated ducts on into stratified cuboidal (to columnar) interlobular ducts in the connective tissue septa.

striatedduct.jpg (38113 bytes)

B. Parotid - The parotid gland is almost exclusively serous. On slide #53 the acini are intermixed with a large proportion of adipose cells. This might help you pick out the various ducts.

C. Sublingual - Mucous tubules predominate in the sublingual glands, slide #54, sometimes with caps of serous cells displaced to the terminal portion of the tubule as darkly staining crescents (demilunes), rather than as distinct acini. The abundance of immune cells, mostly plasma cells, in the connective tissue is especially apparent on this slide.

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PANCREAS

 Contents:
    Pancreas Objectives
    I.  Introduction
    II. Anatomy
       A.  Exocrine anatomy
       B.  Endocrine anatomy
    III.  Functions Summarized
    IV. Clinical Correlations - Acute Pancreatitis
    V.  Laboratory
   

PANCREAS OBJECTIVES

A. Describe the exocrine functions of the pancreas, including how pancreatic function
        is related to and influenced by secretions of the stomach and intestinal epithelium.
B. Describe the histological organization of the pancreas exocrine glands and ducts.
C. Describe the histological organization of the endocrine pancreas, and name two
        major hormones secreted by these cells.

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I.  PANCREAS INTRODUCTION

Like the liver and salivary glands, the pancreas is a lobulated organ surrounded by a thin connective tissue capsule, which extends into the stroma as thin septa. The pancreas, like the liver, is a mixed endocrine and exocrine gland, in this case secreting hormones, such as insulin, into the blood and digestive enzymes into the intestine. Unlike the liver, the pancreas has separate areas for its endocrine and exocrine functions. The endocrine portion is composed of distinct clusters of cells, called islets of Langerhans. The exocrine portion has a compound acinar structure. These exocrine cells secrete an enzyme-rich alkaline fluid into the duodenum via the pancreatic duct.

pancreas.jpg (36031 bytes)

Exocrine pancreatic secretion is continuous, but the rate is regulated primarily by the parasympathetic stimulation from the vagus nerve and by two hormones, secretin and cholecystokinin. These peptide hormones are produced by specialized epithelial cells (enteroendocrine cells) in the duodenum and secreted into the blood in response to a meal. Secretin stimulates pancreatic duct cells to produce a fluid high in bicarbonate and, hence, high in pH. This serves to neutralize the acidic chyme (partially digested food) entering the duodenum from the stomach. Cholecystokinin (mentioned in the liver section with regard to stimulation of bile flow), stimulates pancreatic acinar cells to produce a secretion rich in digestive enzymes, which function optimally at a neutral or slightly alkaline pH.

Among the many digestive enzymes secreted by the pancreas are proteases such as trypsin, chymotrypsin, and carboxypeptidase, nucleases, including both ribo- and deoxyribonucleases, lipases, and amylase. Many of these enzymes are released from the pancreas as inactive proenzymes (e.g. trypsinogen and chymotrypsinogen) and are only activated in the duodenum by action of other enzymes.

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II.  PANCREAS ANATOMY

II.A.  EXOCINE ANATOMY

pancreas-acinus.jpg (49012 bytes)

The exocrine pancreas is composed of closely packed acini draining into a series of branched ducts. The acini are composed of several wedge-shaped serous cells surrounding a central lumen. These are typical polarized secretory cells with a spherical nucleus and a basophilic cytoplasm. Eosinophilic secretory vesicles rich in digestive enzymes (zymogen granules) may be seen toward the apex of each acinar cell. The base of each pyramidal acinar cell lies on the basement membrane which surrounds each acinus. Beneath this basement membrane is a rich capillary network.

pancrexo1.jpg (37773 bytes)

Intercalated ducts lined by simple cuboidal epithelium drain the lumens of the acini into interlobular ducts lined by simple cuboidal to columnar epithelium, which drain into the pancreatic duct. A unique feature of the exocrine pancreas is the presence of centroacinar cells which occur where the intercalated ducts penetrate the acini. The centroacinar cells are pale cells with a central nucleus that are the intra-acinar portion of the intercalated ducts.

pancrexoduct.jpg (38729 bytes)

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II.B.  ENDOCRINE ANATOMY

pancendo1.jpg (59519 bytes)

Interspersed among the exocrine acinar glands are lightly staining, spherical clusters of cells without ducts, acini, or obvious zymogen granules: the endocrine islets of Langerhans. At least 4 different kinds of cells in these clusters, specialized to produce different hormones. Alpha cells stain deep pink by H+E and produce glucagon, which stimulates glycogenolysis and lipolysis in other tissues to raise blood glucose levels. Beta cells stain stain light pink and produce insulin, which has many effects, such as promoting other tissues (particularly liver muscle and adipose tissue) to take up and metabolize glucose, lowering blood sugar levels. Dysfunction or destruction of the beta cells is one of the many causes of diabetes. Excess blood sugar (hyperglycemia) causes excretion of abnormally large volumes of urine rich in glucose. The kinds of islet cells are less numerous and difficult to pick out without special staining techniques. They produce several other hormones. These interspersed endocrine cells are arranged as cords separated by a network of fenestrated capillaries. Both the endocrine cells and the blood vessels are innervated by autonomic nerves.

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III.   FUNCTIONS SUMMARIZED

A. Exocrine
        High pH fluid rich in digestive proenzymes secreted into the duodenum
        Neutralizes acidic chyme from stomach
        Activated enzymes digest proteins, carbohydrates, lipids, and nucleic acids

B. Endocine
        Glucagon - raises blood glucose by stimulating glycogenolysis and lipolysis
        Insulin - lowers blood glucose by stimulating uptake and metabolism

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IV.  CLINICAL CORRELATIONS - Acute Pancreatitis

The release of pancreatic enzymes as inactive proenzymes is important, because if activated prematurely, these powerful lytic enzymes would digest the pancreas. This can happen in acute pancreatitis, caused by infection or injury.

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V. PANCREAS LABORATORY

OBJECTIVES

Be able to identify and describe the organization of both the exocrine and endocrine portions, the major functions and secretory products of each, and the organization of the exocrine ducts.

LABORATORY

A. Exocrine - Most of the pancreas is composed of the exocrine acini. On slides #67- 69 these cells appear as clusters of cells with basal nuclei and very eosinophilic cytoplasm due to many zymogen granules, too small to be resolved. What is in the granules? In some acini you should see pale centroacinar cells, closely resembling the simple cuboidal exocrine duct cells, but appearing to reside almost in the center of the acini. These cells and the intralobular ducts are especially apparent on slide #69. The pancreas is divided into lobules by thin connective tissue septa carrying blood vessels, nerves, lymphatics, and interlobular ducts. These are especially apparent on slide #68. The ducts are lined by simple cuboidal to columnar (in the largest ducts) epithelium.

panc-exo.jpg (32764 bytes)

B. Endocrine - A few scattered clumps of paler staining, loosely organized cells are also seen in slides #67- 69. These are the endocrine islets of Langerhans. The cells are not organized as acini and do not secrete into ducts. Instead, they are interpsersed with a rich plexus of fenestrated capillaries. You may be able to discern pinker staining alpha cells from paler beta cells. What do each of these cells secrete?

 

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Copyright 1997 Regents of the University of California. All Rights Reserved.

Last updated 12/07/98
Douglas N.W. Cooper, Ph.D.       cooper@cgl.ucsf.edu


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