Pancreatic Enzymes Overview

Pancreatic Proteolytic Enzymes

• Pancreatic proteolytic enzymes are secreted in inactive forms: trypsinogen, chymotrypsinogen, and procarboxypeptidase.
• These enzymes are converted to their active forms in the duodenal lumen.
• Trypsinogen is converted to trypsin by enteropeptidase (enterokinase).
• Trypsin activates the other two enzymes, chymotrypsinogen and procarboxypeptidase, to chymotrypsin and carboxypeptidase respectively.
• Pepsinogen is another similar inactive enzyme to trypsinogen.

Pancreatic Amylase

• Digests carbohydrates.
• Cleaves polysaccharides into disaccharides.
• Salivary amylase also digests carbohydrates.

Pancreatic Lipase

• Digests fats.
• Hydrolyzes dietary triglycerides into monoglycerides (MG) and two fatty acids (2FA).

Pancreatic Aqueous Alkaline Secretion

• Pancreatic enzymes function best in a slightly alkaline environment.
• Acidic chyme emptied into the duodenum needs to be neutralized quickly.
• This allows optimal functioning of pancreatic enzymes and prevents acidic damage to the duodenal wall.
• Acidic chyme is neutralized by NaHCO3-rich fluid secreted by the pancreas into the duodenum.
• This aqueous NaHCO3 component is the largest part of pancreatic secretion.

Pancreatic Duct Secretion

• CFTR (Cystic Fibrosis Transmembrane conductance Regulator) channel is responsible for chloride (Cl-) secretion.
• Sodium (Na+) and potassium (K+) also play a role in the process.
• Net secretion of HCO3- and net absorption of H+ leads to pancreatic duct secretion.
• This secretion is different from salivary secretions, which are either isotonic or hypotonic.

Cystic Fibrosis

• Thickened secretions build up in pancreatic ducts, leading to the inability of pancreatic enzymes to reach the duodenum.
• This causes pancreatic exocrine failure in children.
• Insufficient pancreatic digestive enzymes released results in incomplete food digestion.
• The pancreas is a major source of lipase, so with pancreatic enzyme deficiency, fats are maldigested.
• Digestion of proteins and carbohydrates is less affected, however, because salivary, gastric, and small intestinal enzymes contribute towards their digestion.
• Symptoms of cystic fibrosis include:
  • Steatorrhea (excess undigested fat excreted in feces; stools are greasy, odorous, and float).
  • Poor weight gain.
• Children with cystic fibrosis may require pancreatic enzyme supplements.
• The ability to absorb fat-soluble vitamins (A, D, E, and K) is also decreased.

Regulation of Pancreatic Secretion

• Pancreatic exocrine secretion is mainly regulated by hormonal control.
• Major stimulation of pancreatic secretion occurs during the intestinal phase of digestion.
• As chyme enters the small intestine, pancreatic secretion is stimulated.
• Two major enterogastrones are released: secretin and cholecystokinin (CCK).

Secretin

• Secretin is released from S cells in the duodenum.
• Secretin stimulates the pancreas to secrete a bicarbonate-rich fluid that helps neutralize the acidic chyme entering the duodenum.

CCK

• CCK is released from I cells in the duodenum.
• CCK stimulates the pancreas to release digestive enzymes, including proteases, amylases, and lipases.
• It also stimulates gallbladder contraction and relaxation of the sphincter of Oddi, allowing bile to enter the duodenum for fat digestion.

Enzyme Secretion from Pancreatic Acinar Cells

• Gastrin, released during the cephalic and gastric phases, plays a role in enzyme secretion.
• Gastrin-releasing peptide (GRP), also known as bombesin, is important for this pathway.
• Secretin and CCK, released during the intestinal phase, also contribute to enzyme secretion.
• There is inhibitory regulation involved in this process.

Liver

• The liver is a vital organ that performs numerous functions, including:
  • Storage: Glycogen, fat, proteins, and vitamins.
  • Production of cellular fuel: Glucose and fatty acids.
  • Detoxification: Processing of harmful products ingested orally and drugs.
  • Removal: Bacteria and old red blood cells.
  • Synthesis: Plasma proteins and clotting factors (e.g. Prothrombin).
  • Activation: Vitamin D.
  • Secretion: Bile salts.
  • Excretion: Bilirubin.

Liver Structure

• Liver functional units are lobules – hexagonal tissue surrounding a central vein.
• The outer edge of the lobule has three vessels: Portal triad (hepatic artery, portal vein, and bile duct).

Bile Salts

• Bile salts are amphipathic; they have both hydrophilic and hydrophobic regions enabling them to interact with both water and fats.
• They are important in fat digestion by emulsifying fats, increasing their surface area for lipase action.
• Bile salts are reabsorbed from the small intestine and recycled into the liver, a process called the enterohepatic circulation.

Bilirubin

• Bilirubin is a yellow pigment and a waste product of heme breakdown from old red blood cells.
• It is not involved in digestion and is excreted in bile.
• Hepatocytes take up bilirubin, modify it for increased solubility, and excrete it into bile.
• Bacterial enzymes modify bilirubin in the intestines, giving feces its normal color.
• If bile secretions are blocked, fecal color will change to a more greyish color.
• Small amounts of bilirubin are reabsorbed from the intestines and excreted in urine, giving urine its typical color.

Cirrhosis

• Cirrhosis is prolonged hepatic inflammation, often associated with alcohol intake (over 60% of cases in the US).
• Damaged hepatocytes are replaced by connective tissue and collagen deposition, reducing active liver tissue and leading to chronic liver failure.
• Symptoms:
  • Jaundice.
  • Weight loss.
  • Abdominal pain.
  • Abdominal ascites (fluid retention).
• Treatment:
  • Abstinence from alcohol.
  • Diuretics.
  • Antibiotics.