The Pancreas and Liver

Hello :) In this post, we'll be discussing the roles of the pancreas and liver. I'll describe the general structure of the exocrine pancreas, list the main enzymes produced by the pancreas and what they do. I'll also explain the mechanisms of pancreatic duct secretion and the neurohormonal regulation of secretion. We'll also go over the structure of the liver, as well as take a look at bile salts and bilirubin.

Just briefly before we begin, it's important to understand the general role of the pancreas and liver. Digesta that is emptied from the stomach (or abomasum in ruminants) enters the duodenum. Here it is modified by secretions from the exocrine pancreas and liver. The bicarbonate secreted in pancreatic fluids is particularly important because it works to neutralise the acidic digesta which has come from the stomach. This spares the duodenal mucosa from acid damage and provides an optimum pH for pancreatic enzyme activity.

The Structure of the Exocrine Pancreas

The exocrine pancreas is arranged anatomically like a salivary gland. Its functional unit is the acinius and draining ductule. The acinar cells synthesise and secrete digestive enzymes which are stored in the zymogen granules positioned on the apical side of the cells. The basolateral membrane of the cells have receptors for hormones and neurotransmitters that regulate secretion. Duct epithelial cells are responsible for secreting bicarbonate ions. The basolateral membrane of the duct epithelial cells also have receptors for hormones and neurotransmitters that regulate secretion. Fluid flows along these ducts and empties into the duodenum.

Pancreatic Enzymes

 The proteolytic enzymes include trypsin, chymotrypsin and carboxypeptidase. These are secreted in their inactive forms. Trypsinogen is converted to trypsin by an enzyme called enterokinase. Trypsin then activates the other two proteolytic enzymes. Trypsin and chymotrypsin split the proteins into peptides but do not release individual amino acids. Carboxypeptidase splits some proteins into the component amino acids. The acinar cells which secrete the proteolytic enzymes also produce a trypsin inhibitor which prevents these enzymes from damaging the pancreas. 

The amylase enzymes include α-amylase which is secreted by the pancreas and the salivary glands. These digest starch to maltose and maltotriose while complete hydrolysis to monosaccharides is done by the brush border enzymes in the small intestine. The secretion of amylase is stimulated by diets high in starch.

The main lipolytic enzyme is lipase which is important in fat digestion. However, in order for fats to be digested bile salts are also required. In the presence of bile salts the hydrolysis of fats by lipase allows for the formation of water-soluble micelles. The secretion of lipase is stimulated by diets high in fat or high in protein.

 The Mechanisms of Pancreatic Duct Secretion

 Bicarbonate, water and electrolytes are mainly secreted from the epithelial cells of the duct system. As the concentration of bicarbonate increases in the fluid, the concentration of Cl- decreases. In addition to bicarbonate, pancreatic fluid also contains water, sodium and potassium.

 

 The mechanism of secretion is as follows: 

• Carbon dioxide enters the duct cell and mixes with water. 
• This is converted to carbonic acid by carbonic anhydrase. Carbonic acid then breaks down into H+ and HCO3-.
• This bicarbonate exits the apical membrane of the cell through a HCO3-/Cl- counter transporter. Bicarbonate also enters the cell through the basolateral membrane through a type 1 sodium/bicarbonate co transporter (NBC-1) and exits the cell in the same way. 
• Cl- exits through the cystic fibrosis transmembrane conductance regulator (CFTR).
• The H+ exits the basolateral membrane via a type 1 sodium-hydrogen exchanger (NHE-1). Here the H+ combines with HCO3- to form carbonic acid which breaks up into carbon dioxide and water. This carbon dioxide enters the cell through the first step. 
• A Na+/K+ pump also exists on the basolateral membrane. This exports Na+ out the cell and creates a concentration gradient which allows the NBC-1 and NHE-1 transporters to work. 

  

The faster the pancreatic fluid flows through the ducts, the more bicarbonate and less chloride will be present in the fluid. However, the concentrations of sodium and potassium will remain the same. Sodium concentrations will remain fairly high while potassium concentrations are low.

Cholecystokinin (CCK) and Acetylcholine are the main regulators of pancreatic enzyme secretion. In the cephalic and gastric phases of pancreatic secretion, vagal cholinergic nerve fibres stimulate M3 receptors in the acnini and this stimulates enzyme secretion. During these phases of secretion, only small amounts of  water and electrolytes are secreted. During the intestinal phase of secretion, secretin is released from S cells in response to H+ in the gastric chyme entering the duodenum. This stimulates copius amounts of bicarbonate and water to be secreted from the ducts. Secretin induced secretion requires sholinergic input. Also during the intestinal phase, CCK is released from I cells in response to fat entering in the gastric chyme. This mediates acinar enzyme secretion and also requires cholinergic input.  

The Liver

The liver receives blood from both the hepatic artery and portal vein and in healthy animals uses about 25% of the cardiac output. The liver performs many functions, particularly the metabolism of carbohydrates, proteins and fats, and secretes bile. Bile has an important role in the digestion of fats. The liver is also the body's first line of defence against toxins and other chemicals absorbed via the GIT. 

Structure

The liver consists of sheets of six-sided hepatocytes which are arranged into lobules and bathed by sinusoidal blood on two sides. Bile flows through cannaliculi which are situated between each row of hepatocytes. The composition of bile is changed within the biliary ducts by the addition of water and bicarbonate. This website has a diagram of the microscopic structure of the liver which you may find useful :)

Blood flows towards the central vein of the lobule while bile flows in the opposite direction.

Bile Acids

Bile acids are synthesised from cholesterol by hepatocytes and thus have a chemical structure which is similar to cholesterol. Bile acids have both a hydrophilic and hydrophobic side and this enables them to make lipids soluble in water (they emulsify them). The representative bile acid is Cholic acid, its structure is shown below. 

The Structure of Cholic Acid

In the liver the bile acids are conjugated with taurine or glycine, this decreases the dissociation constant which means they are excreted in the bile as bile salts. 

Because bile salts are not fat soluble they remain in the lumen of the small intestine and this allows them to form micelles which are important in fat absorption. The bile salts are reabsorbed through an active process in the distal ileum or are degraded to secondary bile acids by intestinal bacteria. 95% of bile acids are recycled to the liver via portal circulation.  

When the bile is produced by the hepatocytes it has a similar ionic composition to blood. However, the volume and ionic composition is altered during the flow through the ducts and storage in the gall bladder. In ducts, secretin stimulates the secretion of bicarbonate while in the gall bladder bile is concentrated by the active reabsorption of sodium, chloride and bicarbonate (which causes water to follow). 

Bilirubin

Bilirubin is a product of the breakdown of haemoproteins from erythrocytes which are too old. The iron from the haemoglobin is recycled but the haeme pigments are broken down to bilirubin which is water insoluble. Thus, it is transported in the blood bound to albumin. It is then absorbed by the cells of the liver and conjugated into glucuronides. These are secreted in the bile and reduced by intestinal bacteria to form urobilinogen. Urobiliniogen is absorbed by the small intestine and is excreted in the urine or oxidised to stercobilin (this is responsible for the brown colour of stool). 

That's it for this post, please feel free to leave any questions or suggestions in the comments section below :)