The exocrine units of the pancreas are tubuloacinar glands that are organized like bunches of grapes (Fig. 5.3), in a similar manner to the units in the salivary glands. The exocrine units surround the islets of Langerhans, the endocrine units of the pancreas. For this reason, destructive diseases such as chronic pancreatitis involve impairment of both exocrine and endocrine function. A thin layer of loose connective tissue surrounds the gland. Septa extend from this layer into the gland, dividing it into lobules and giving it an irregular surface. Larger areas of connective tissue surround the main ducts and the blood vessels and nerve fibres that penetrate the gland. Small mucous glands situated within the tissue surrounding the pancreatic duct secrete mucus into the duct.

The endocrine units, or islets of Langerhans, are most numerous in the tail region of the pancreas. They consist of clusters of cells which are surrounded by the pancreatic acini (Fig. 5.3). The islets vary considerably in size. As with all endocrine tissue, the hormones they produce are secreted into the blood. The major endocrine cell types present are: α, β, D and PP cells, which secrete glucagon, insulin, somatostatin, and pancreatic polypeptide, respectively (for more information, see Ch. 9). Different types of endocrine cells can be distinguished under the electron microscope by the different appearance of the granules within them. The islet cells have the general features of APUD cells (see Ch. 1). In addition, there are a few (<5%) small ‘clear’ cells with as yet no clearly defined function.

Glucagon and insulin, the hormones produced by the α and β cells, respectively, are taken up by the local blood vessels to act systemically. Somatostatin acts locally in a paracrine manner to inhibit the secretion of the α and β cells, as well as the exocrine secretions of the acinar and duct cells. Pancreatic polypeptide acts in a paracrine manner to inhibit the exocrine secretions of the pancreas.

Oxygenated blood is supplied to the pancreas by branches of the coeliac and superior mesenteric arteries. The pancreatico-duodenal artery lies between the duodenum and the head of the pancreas. The close proximity of these structures means that it would be hazardous to remove the pancreas without the duodenum, because the main arterial supply would inevitably be damaged. The blood drains from the pancreas via the portal vein to the liver. This arrangement is important for the transport of pancreatic hormones to the liver where they contribute to the control of energy metabolism, a topic discussed in Chapter 9. The acini and ducts are surrounded by separate capillary beds. Some of the capillaries that supply the islets converge to form efferent arterioles which then enter further capillary networks around the acini. This arrangement is important for the paracrine control of pancreatic exocrine secretion.

Cholinergic preganglionic fibres of the vagus nerve enter the pancreas. These synapse with postganglionic cholinergic nerve fibres which lie within the pancreatic tissue and innervate both acinar and islet cells. Postganglionic sympathetic nerves from the coeliac and superior mesenteric plexi innervate the pancreatic blood vessels as well as the acinar and duct cells.

Figure 5.3 shows the structure of a pancreatic lobule. The exocrine units of the pancreas, or pancreatins, each consist of a terminal acinar portion and a duct (Fig. 5.4). The duct that drains the acinus is known as an intercalated duct. These empty into larger intralobular ducts. The intralobular ducts in each lobule drain into a larger extralobular duct that empties the secretions of that lobule into still larger ducts, and the latter converge into the main collecting duct, the pancreatic duct.

The acinus is a rounded structure consisting of mainly pyramidal epithelial cells (Fig. 5.4). These cells secrete the digestive enzymes of the pancreatic juice. They display polarized features that are common to secretory cells (Fig. 5.3). The nucleus of the acinar cell is situated at the base of the cell. The cytoplasm in the basal region can be stained with haematoxylin or basic dyes due to the presence of rough endoplasmic reticulum, the site of production of the digestive enzymes. Small mitochondria are situated throughout the cell. The apical portion of the cell contains the Golgi apparatus, and numerous zymogen granules that contain the pancreatic enzymes or their precursors. The apical region therefore stains with acid dyes such as eosin. Microvilli extend from the apical surface of the acinar cell into the lumen. The apical poles of neighbouring cells are joined by tight junctions, known as zonulae adherens. These junctions separate the fluid in the lumen of the acinus from the fluid in the intercellular spaces that bathes the basolateral surfaces of the cells. The tight junctions are impermeable to macromolecules, such as digestive enzymes, in the luminal fluid, but permit the exchange of water and ions between the interstitial spaces and the lumen of the acinus. Disruption of these junctions may be an aetiological factor in the development of chronic pancreatitis. Gap junctions between neighbouring cells allow rapid changes in membrane potential to be transmitted between the cells. They also permit the exchange of low molecular weight molecules (<1400kDa mass) between cells.

The intercalated duct begins within the acinus. This is a unique feature of secretory glands. The upper duct cells within the acinus are known as centroacinar cells (Fig. 5.4). These stain lightly with eosin. They are squamous cells with a centrally placed nucleus. These cells are continuous with those of the short intercalated duct that lies outside the acinus and drains it. The intercalated ducts are lined by flattened squamous epithelial cells. The neighbouring duct cells are joined by tight junctions, as in the acinus. These separate the duct lumen from the intercellular spaces and function to exclude large molecules from the spaces. They also have gap junctions that permit the transmission of membrane electrical changes between the cells. These ducts lead into the intralobular ducts that are lined with cuboidal or low columnar epithelium. Larger ducts contain interlobular connective tissue cells and APUD cells.

The cells of the upper ducts secrete an isotonic juice which is rich in bicarbonate but contains only traces of enzymes. There is a continuous resting secretion of this juice, but it can be stimulated up to 14-fold during a meal. It contains Na⁺, K⁺, HCO₃⁻, Mg²⁺, Ca²⁺, Cl⁻ and other ions present in concentrations similar to those of plasma. It therefore resembles an ultrafiltrate of plasma, but is alkaline by virtue of its high HCO₃⁻ content.

The pancreatic juice arriving in the duodenum is mixed with the chyme by contractions of the smooth muscle of the small intestine. The function of the alkaline pancreatic secretion, together with the other alkaline secretions (bile and intestinal juices) that act in the small intestine, is to neutralize the acid chyme arriving from the stomach. This is important for several reasons:

The mechanisms involved in the production of intracellular HCO₃⁻ in the centroacinar and upper duct cells are illustrated in Figure 5.5. The initial intracellular step involves the reaction of CO₂ with water. Secreted H⁺ ions react with HCO₃⁻ ions in the blood perfusing the gland and this generates CO₂, some of which diffuses into the duct cell. More than 90% of the HCO₃⁻ in pancreatic juice is derived from blood CO₂. In the cell, the CO₂ combines with intracellular water to generate carbonic acid, in a reaction catalysed by carbonic anhydrase II, an enzyme present in the centroacinar and upper duct cells. The carbonic acid dissociates to give HCO₃⁻ and H⁺. Whilst bicarbonate is being secreted the partial pressure of CO₂ (pCO₂) in the cells is lower than in the blood as it is being used up in the production of HCO₃⁻ ions, and the higher the rate of secretion the greater the downhill gradient for diffusion of CO₂ into the cell. The HCO₃⁻ ions are secreted across the luminal membrane by Cl⁻/HCO₃⁻ exchange, and the H⁺ ions are secreted into the blood. Thus for every HCO₃⁻ ion that is secreted into the duct lumen one H⁺ ion is secreted into the blood. Therefore the blood flowing through the pancreas becomes transiently acid when it is secreting HCO₃⁻. The H⁺ ions in the blood help to neutralize the ‘alkaline tide’ produced during a meal by the secreting stomach (see Ch. 3), by combining with plasma HCO₃⁻ to produce CO₂. In conditions where a patient is provided with a pancreatic fistula, loss of HCO₃⁻ must be carefully monitored (Box 5.1).