Physiology, Digestion

Cellular Level

Digestion begins immediately in the oral cavity with both mechanical and chemical digestion. Mechanical digestion in the oral cavity consists of grinding food into smaller pieces by the teeth, a process called mastication. Chemical digestion in the mouth is minor but consists of salivary amylase (ptyalin, or alpha-amylase) and lingual lipase, both contained in the saliva. Salivary amylase is chemically identical to pancreatic amylase and digests starch into maltose and maltotriose, working at a pH optimum of 6.7 to 7.0. Lingual lipase, also contained in the saliva, hydrolyzes triglyceride ester bonds to form diacylglycerols and monoacylglycerols.[1] After sufficient digestion in the oral cavity, the partially digested foodstuff, or bolus, is swallowed into the esophagus. No digestion occurs in the esophagus.

After passage through the esophagus, the bolus enters the stomach and undergoes mechanical and chemical digestion. Mechanical digestion in the stomach occurs via peristaltic contractions of the smooth muscle from the fundus towards the contracted pylorus, termed propulsion. Once the bolus is near the pylorus, the antrum functions to grind the material by forceful peristaltic contractions that force the bolus against a tightly constricted pylorus. The churning by the antrum reduces the size of the food particles and is called grinding. Only particles smaller than 2mm in diameter can pass through the contracted pylorus into the duodenum. The rest of the bolus is pushed back towards the body of the stomach for further mechanical and chemical digestion. This backward movement of the bolus from the pylorus to the body is termed retropulsion and aids in mechanical digestion. This propulsion, grinding, and retropulsion sequence repeats until the food particles are small enough to pass through the pylorus into the duodenum. All chyme not pushed through the pylorus during active digestion is eventually swept into the duodenum through a relaxed pylorus by a series of strong peristaltic contractions in the stomach. This activity occurs during the inter-digestive phase called migrating motor complexes (MMCs) that move the bolus in an aboral fashion to prevent stagnation and bacterial accumulation.

There is significant chemical digestion in the stomach. Two types of glands in the gastric mucosa aid in chemical digestion: oxyntic glands and pyloric glands. Oxyntic glands are located in the body of the stomach and contain parietal cells and chief cells. Parietal cells secrete hydrochloric acid, concentrated to approximately 160 mmol/L and a pH of 0.8. Hydrochloric acid secreted by the parietal cells serves 3 main functions: 1) to create a hostile environment for pathogenic microorganisms taken in through the mouth, 2) to denature proteins and make them more accessible for enzymatic degradation by pepsin, and 3) to activate the zymogen pepsinogen to its active form, pepsin. Parietal cells also secrete intrinsic factor, which is necessary to absorb Vitamin B12 in the terminal ileum. Oxyntic glands also contain chief cells that secrete the zymogen pepsinogen. Pepsinogen is the precursor to the proteolytic enzyme pepsin and must be activated to pepsin by the acidic pH of the stomach (below 3.5) or from autoactivation by pepsin itself. Pepsin then acts on the internal peptide bonds of proteins at the optimal pH of 2 to 3. The pyloric glands are found in the antrum of the stomach and contain mucous cells and G-cells. Mucous cells secrete a bicarbonate-rich mucous onto the surface of the gastric mucosa to protect it from the stomach's acidic contents. The G-cells secrete gastrin, a hormone that acts in an endocrine fashion to stimulate the secretion of hydrochloric acid by parietal cells.[2] No digestion of carbohydrates occurs in the stomach.

The majority of chemical digestion occurs in the small intestine. Digested chyme from the stomach passes through the pylorus and into the duodenum. Here, chyme mixes with secretions from the pancreas and the duodenum. Mechanical digestion still occurs to a minor extent as well. The pancreas produces many digestive enzymes, including pancreatic amylase, pancreatic lipase, trypsinogen, chymotrypsinogen, procarboxypeptidase, and proelastase.[3] These enzymes are separated from the stomach's acidic environment and function optimally in the more basic environment of the small intestine, where the pH ranges from 6 to 7 due to bicarbonate secreted by the pancreas. Pancreatic amylase, like salivary amylase, digests starch into maltose and maltotriose. Pancreatic lipase, secreted by the pancreas with an important coenzyme called colipase, functions to hydrolyze the ester bonds in triglycerides to form diacylglycerols and monoacylglycerols. Trypsinogen, chymotrypsinogen, procarboxypeptidase, and proelastase are all precursors to active peptidases. The pancreas does not secrete the active form of the peptidases; otherwise, autodigestion could occur, as is the pancreatitis case. Instead, trypsinogen, chymotrypsinogen, procarboxypeptidase, and proelastase convert to trypsin, chymotrypsin, carboxypeptidase, and elastase, respectively.[3] This conversion occurs as enterokinase, a duodenal enzyme, converts trypsinogen to trypsin. Trypsin can then convert chymotrypsinogen, procarboxypeptidase, and proelastase to their active forms. Trypsin, chymotrypsin, and elastase are all endopeptidases that hydrolyze internal peptide bonds of proteins, while carboxypeptidases are exopeptidases that hydrolyze terminal peptide bonds on proteins. These pancreatic zymogens leave the pancreas through the main pancreatic duct (of Wirsung) and join the common bile duct, forming the ampulla of Vater and emptying into the descending portion of the duodenum via the major duodenal papilla. The common bile duct carries bile made in the liver and stored in the gallbladder. Bile contains a mixture of bile salts, cholesterol, fatty acids, bilirubin, and electrolytes that help emulsify hydrophobic lipids in the small intestine, which is necessary for access and action by pancreatic lipase, which is hydrophilic.

Once in the duodenum, an activation cascade begins with enterokinase produced by the duodenum to activate trypsinogen to trypsin, and trypsin activates the other pancreatic peptidases. The duodenum also contributes digestive enzymes, such as disaccharidases and dipeptidase. The disaccharidases include maltase, lactase, and sucrase. Maltase cleaves the glycosidic bond in maltose, producing 2 glucose monomers, lactase cleaves the glycosidic bond in lactose, producing glucose and galactose, and sucrase cleaves the glycosidic bond in sucrose, producing glucose and fructose. Dipeptidase cleaves the peptide bond in dipeptides. At this point, the mouth, stomach, and small intestine have broken down fat in the form of triglycerides to fatty acids and monoacylglycerol, carbohydrates in the form of starch and disaccharides to monosaccharides, and large proteins into amino acids and oligopeptides. Thus, the digestive process has converted macronutrients into absorbable forms in the bloodstream for bodily use.[4]

Organ Systems Involved

The gastrointestinal system includes:

• Oral cavity
• Stomach
• Small intestine
• Liver
• Gall bladder
• Pancreas

Function

Digestion is a process that converts nutrients in ingested food into forms that the gastrointestinal tract can absorb. Proper digestion requires mechanical and chemical digestion and occurs in the oral cavity, stomach, and small intestine. Additionally, digestion requires secretions from accessory digestive organs such as the pancreas, liver, and gallbladder. The oral cavity, stomach, and small intestine are 3 separate digestive compartments with differing chemical environments. The oral cavity provides significant mechanical digestive functions and minor chemical digestion at a pH between 6.7 and 7.0. The oral cavity requires separation from the stomach's acidic environment with a pH of 0.8 to 3.5. As such, enzymes such as alpha-amylase secreted by salivary glands in the oral cavity and the pancreas cannot function in the stomach, and thus, digestion of carbohydrates does not occur in the stomach. However, in the stomach, significant digestion of proteins into polypeptides and oligopeptides occurs by the action of pepsin, which functions optimally at a pH of 2.0 to 3.0.

Minor digestion of lipids into fatty acids and monoacylglycerols also occurs by the action of gastric lipase secreted by chief cells in oxyntic glands of the body of the stomach. Importantly, the tonically constricted pylorus also separates this acidic environment of the stomach from the more basic environment of the small intestine. This creates an environment where the digestive enzymes produced by the pancreas and duodenum can function optimally at a pH of 6 to 7, a more basic environment than the stomach created by bicarbonate secreted by the pancreas. These separate yet coordinated digestive functions are essential to the body’s ability to absorb and utilize necessary nutrients. A defect in any aspect of this process can result in malabsorption and malnutrition, amongst other gastrointestinal pathologies.

Related Testing

Clinical tests for defects in digestion or deficiencies in digestive enzymes are often indicated after a patient presents with gastrointestinal symptoms. An example is testing for lactose intolerance due to a lactase defect or deficiency. Lactase is a disaccharidase produced by the pancreas that hydrolyzes the glycosidic bond in lactose to form the carbohydrate monomers glucose and galactose; this is necessary, as glucose and galactose are absorbable by the SGLT1 cotransporters on the luminal surface of enterocytes in the small intestine, but lactose cannot.[5] As such, in lactose intolerance, lactose remains undigested in the lumen of the small intestine and serves as an osmotic force that draws fluid into the lumen of the small intestine, causing osmotic diarrhea. A common test for lactose intolerance involves administering a bolus of lactose to the patient. Blood glucose levels are then measured at periodic intervals. In a patient with normal lactase function, blood glucose levels rise after oral administration of a lactose bolus because lactase digests lactose into glucose and galactose, which is absorbed into the bloodstream. Thus, blood glucose levels rise.

In a patient with defective or deficient lactase, a rise in blood glucose levels after oral administration of a lactose bolus does not occur because lactose remains undigested in the lumen of the small intestine, and no glucose enters the bloodstream. A second test for lactose intolerance involves a similar administration of oral lactose and then a measurement of hydrogen gas levels in the breath. In a patient with lactose intolerance, lactose remains undigested and passes into the colon. Colonic bacteria can use lactose as an energy source, producing hydrogen gas as a byproduct.[6] This production of hydrogen gas by colonic bacteria not only causes bloating and flatulence but is also measurable during exhalation. Thus, a patient with lactose intolerance shows increased hydrogen gas levels in the breath after administration of oral lactose, whereas a patient with normal lactase function does not.[7]

Clinical Significance

Defects in any aspect of digestion can result in uncomfortable gastrointestinal symptoms and the inability to absorb certain nutrients. Several digestion defects are discussed below.

As mentioned previously, lactose intolerance results from defective or deficient lactase and can result in bloating, flatulence, diarrhea, and the inability to acquire glucose and galactose from lactose. Management can involve avoiding dairy products, which contain significant amounts of lactose. In this case, supplemental calcium may be necessary. Additionally, beta-galactosidase (lactase) tablets are available as supplements for people who are lactose intolerant.

Paralytic ileus is a condition where the normal peristaltic movements of the gastrointestinal tract are inhibited due to abdominal surgery or anticholinergics. Inhibitory neurons in the myenteric plexus between the inner circular and outer longitudinal muscle layers of the gastrointestinal tract release excessive vasoactive intestinal peptide (VIP) or nitric oxide (NO), inhibitory neurotransmitters that prevent peristalsis. Anticholinergics can interfere with the action of acetylcholine, a stimulatory neurotransmitter from the parasympathetic nervous system that stimulates peristalsis. In both cases, peristalsis is inhibited, hindering food's movement and mechanical digestion through the gastrointestinal tract.

Sjogren syndrome is an autoimmune condition that destroys the salivary and lacrimal glands. Without the production of saliva, the patient develops xerostomia or dry mouth. The lack of saliva results in difficulty speaking and swallowing, dental caries, and halitosis.[8]

Zollinger-Ellison syndrome is a condition where a gastrinoma produces excessive gastrin, leading to overstimulation of gastric parietal cells and excessive hydrochloric acid production. This can result in ulceration of the lining of the gastrointestinal tract, extreme discomfort, and hematemesis. Treatment includes proton pump inhibitors such as omeprazole, H2 receptor antagonists such as ranitidine, and removal of the offending tumor.[9]

Aside from respiratory effects, cystic fibrosis also affects the digestive tract. In cystic fibrosis, the CFTR chloride channel is defective. This channel is important in the pancreas for transporting chloride into the lumen of the pancreatic ducts to draw Na and water into the lumen. This makes the pancreatic secretions less viscous and allows their passage through the duct of Wirsung and into the duodenum. If this CFTR chloride channel is defective, as in cystic fibrosis, the pancreatic secretions become extremely viscous and clog the pancreatic ducts.[10] This prevents the digestion of proteins, fats, and carbohydrates in the lumen of the small intestine but also causes premature activation of pancreatic digestive enzymes within the pancreas, causing autodigestion and pancreatitis. The inability to digest fats can lead to steatorrhea and fat-soluble vitamin deficiencies. Patients with pancreatic insufficiency secondary to cystic fibrosis or other causes can take oral pancreatic enzyme supplements to aid digestion.

Cholelithiasis, or gallstones, are solidified particles of bile that can obstruct the common bile duct. This results in the inability of bile to enter the lumen of the duodenum, and, as such, fats are not emulsified. Pancreatic lipase cannot access the triglycerides, and fats remain undigested. This also results in steatorrhea and can lead to deficiencies in fat-soluble vitamins. Treatment often involves the removal of the gallbladder or cholecystectomy.[11]