Introduction

The gastrointestinal system comprises the gastrointestinal tract and accessory organs. The gastrointestinal tract consists of the oral cavity, pharynx, esophagus, stomach, small intestine, large intestine, and anal canal. The accessory organs include the teeth, tongue, and glandular organs such as salivary glands, liver, gallbladder, and pancreas. The main functions of the GI system include ingestion and digestion of food, nutrient absorption, secretion of water and enzymes, and excretion of waste products.

Issues of Concern

The gastrointestinal system is complex, and the amount of material that could be covered is substantial. Therefore, this topic provides an overview of gastrointestinal tract physiology, with links to references that delve deeper into complex topics.

Cellular Level

There are 4 histologic layers of the gastrointestinal tract. From the lumen outward:

Mucosa 

The mucosa consists of a single layer of epithelium, which is highly folded to increase its surface area for absorption. The mucosa contains invaginations, which form tubular exocrine glands that secrete mucus, electrolytes, water, and digestive enzymes. It also houses endocrine glands that release gastrointestinal hormones such as cholecystokinin (CCK). The lamina propria, a connective tissue layer, supports the epithelium.

Submucosa

The submucosa, a connective tissue layer, houses blood and lymphatic vessels that support the gastrointestinal tract. The submucosal (Meissner) plexus is found in this layer.

Muscularis Externa 

The muscularis externa comprises 2 major smooth muscle layers: an inner circular and an outer longitudinal muscular layer. Between these 2 layers, the myenteric (Auerbach) plexus is found. The coordinated contraction of the muscular layers via the myenteric plexus controls peristalsis. Of note, the stomach contains a third muscular layer, the inner oblique, which assists in churning the stomach contents. 

Serosa and A dventitia

The serosa is a smooth membrane comprising a thin layer of connective tissue and a thin layer of cells that secrete serous fluid to lubricate internal structures. This lubricating fluid helps reduce friction during movement. The serosa covers intraperitoneal organs, while the adventitia covers retroperitoneal organs and serves to hold structures together rather than reduce friction between them.

Development

The digestive tube begins to form during the third week of gestation. During this time, gastrulation occurs, and 3 germ layers (ectoderm, mesoderm, and endoderm) are formed. The endoderm forms the epithelial lining of the gastrointestinal tract, gallbladder, pancreas, and liver. The mesoderm gives rise to the connective tissue and smooth muscle of the gut tube wall. The ectoderm separates into the surface ectoderm, neural tube, and neural crest. The neural crest forms the peripheral nervous system, including the enteric nervous system, which contains the neurons of the gastrointestinal tract.[1]

Function

The function of the digestive system is to digest and absorb food and then excrete the waste products with the help of the liver, gallbladder, pancreas, small intestine, large intestine, and rectum. Each of these organs plays a specific role in the digestive system. The oral cavity has 4 main functions. First, it provides sensory analysis of food material before swallowing and mechanical processing by the teeth, tongue, and palatal surfaces. The oral cavity also provides lubrication by mixing food material with mucus and salivary gland secretions, and limited digestion of carbohydrates and lipids.

The oral mucosa is lined by both keratinized (seen on the superior surface of the tongue and the hard palate) and nonkeratinized squamous epithelial cells (seen on the cheeks, lips, and inferior surface of the tongue), neither of which is known to aid in absorption, except for the mucosa inferior to the tongue. Functions of the tongue include mechanical processing of food material by compression, abrasion, and distortion; manipulation to assist in chewing and preparing material for swallowing; sensory analysis by touch, temperature, and taste receptors; and secretion of mucins and lingual lipase. The lingual lipase has a broad pH range and breaks down lipids (mainly triglycerides). A pH of 3.5 to 6 allows lingual lipase to work even in the stomach's acidic environment.[2]

Within the oral cavity, there are 3 pairs of salivary glands. The first pair is the parotid salivary glands, located inferior to the zygomatic arch and posterolateral to the mandible. The parotid glands produce serous secretions containing a large amount of salivary amylase, which breaks down carbohydrate complexes. Next are the sublingual salivary glands located on the floor of the mouth. The sublingual glands produce a mucous secretion that serves as both a buffer and a lubricant. The third is the submandibular salivary glands, located on the floor of the mouth within the mandibular groove. They function by secreting a mixture of buffers, glycoproteins called mucins, and salivary amylase.

Altogether, these glands produce 1.0 to 1.5 liters of saliva each day.[3] Close to 99.4% of the saliva produced is water, and the remaining 0.6% consists of electrolytes, buffers, glycoproteins (mucins), antibodies, enzymes, and waste products. These function to lubricate the mouth to prevent friction between the mucosa of the oral cavity and the food material, moisten the food material for easy swallowing, and initiate lipid and carbohydrate complex digestion. The teeth provide a mechanical breakdown of food materials, for instance, the connective tissue of meat and plant fibers in vegetables. This process also saturates the salivary secretions and enzymes within the food material for better digestion. The pharynx serves as a passageway for food material to the esophagus. During swallowing, closure of the nasopharynx and larynx occurs to maintain the proper direction of food; a process achieved by cranial nerves IX and X. From the pharynx, food material goes to the esophagus.

The primary function of the esophagus is to transport food materials into the stomach via waves of contraction of its longitudinal and circular muscles, known as peristalsis. The upper one-third of the esophagus is predominantly skeletal muscle, the middle one-third is a mixture of skeletal and smooth muscle, and the lower one-third is primarily smooth muscle. However, during deglutition, the buccal phase is the only voluntary phase where one can still control the swallowing process. The skeletal muscles in the pharynx and upper esophagus are controlled by the swallow reflex; hence, the pharyngeal and esophageal phases of swallowing are under involuntary control via afferent and efferent fibers of glossopharyngeal and vagus nerves. The smooth muscles of the esophagus are arranged circularly and longitudinally and aid in peristaltic movement during swallowing.[4][5]

Once the food material arrives in the stomach, it can be temporarily stored and mechanically and chemically broken down by stomach acid and enzymes. The secretion of intrinsic factor by the stomach helps ensure appropriate absorption of vitamin B12.[6] The stomach's ability to store food stems from its compliance and capacity to change size. On average, the lesser curvature of the stomach has a length of approximately 10 cm, and the larger curvature has a length of roughly 40 cm. The stomach typically spans from vertebrae T7 to L3, allowing it to hold a large amount of food.

The stomach's ability to mechanically break down food is due to its sophisticated muscular structure. The stomach has 3 muscular layers: an inner oblique layer, a middle circular layer, and an external longitudinal layer. The contraction and relaxation of these 3 muscular layers of the stomach assist in the mixing and churning that are essential for the formation of chyme. Then the chemical breakdown of food material in the stomach is propagated by the gastric glands, produced mainly by the parietal cells, chief cells, G-cells, foveolar cells, and mucous neck cells.

The parietal cells secrete intrinsic factors and hydrochloric acid. The intrinsic factor produced is essential in the absorption of vitamin B12. It binds to B12, allowing for proper absorption at the ileum of the small intestine.[7] The hydrochloric acid produced by the parietal cell keeps the stomach pH between 1.5 and 2.0. The stomach acidity brought on by hydrochloric acid destroys most of the microorganisms ingested with food, denatures protein, breaks down plant cell walls, and is essential for the activation and function of pepsin, a protein-digesting enzyme secreted by chief cells. The chief cells produce a zymogen called pepsinogen, which gets activated at a pH between 1.5 and 2 to become pepsin. Pepsin is a protein-digesting enzyme. The foveolar and mucous neck cells produce mucus, protecting the gastric epithelium from corrosive acid.[8] The G cells are abundant within the pyloric section of the stomach. They produce gastrin, which stimulates secretions from the parietal and chief cells. Within the pyloric glands of the stomach, D cells produce somatostatin, which inhibits gastrin release.[9]

Chyme is directed to the small intestine, where digestion continues. Unlike the stomach, which has minor absorptive properties, 90% of food absorption occurs in the small intestine. The small intestine has 3 segments: the duodenum, the jejunum, and the ileum. The duodenum receives chyme from the stomach and digestive material from the pancreas and the liver. The jejunum is where the bulk of chemical digestion and absorption occurs. The ileum also has both digestive and absorptive functions. The ileum is the last segment of the small intestine and contains the ileocecal valve, a sphincter that controls the flow of material from the ileum to the cecum of the large intestine.

The small intestine mucosa has villi, and each villus has multiple microvilli, which increase the surface area for optimal absorption.[10] There are extensive networks of capillaries within the villi that carry absorbed nutrients to the hepatic portal circulation. Also, many lymphatic capillaries called lacteals aid in chylomicron transportation to the venous circulation. The intestine has both endocrine and exocrine glands that produce hormones, enzymes, and alkaline mucinous material. Some hormones released by the small intestine are listed below:

• Gastrin is produced by G-cells in the upper small intestine (but primarily found in the stomach)
• Cholecystokinin (CCK) is produced by I-cells in the upper small intestine
• Secretin is produced by S-cells in the upper small intestine in response to decreased upper intestine pH
• Gastric inhibitory peptide (GIP) is produced by K-cells in the upper small intestine in response to fat, amino acids, and glucose
• Pro-glucagon is produced by L-cells in the distal ileum and colon in response to glucose and fat
• Somatostatin is produced by D-cells in the small intestine, including the stomach and pancreas
• Vasoactive intestinal polypeptide (VIP) is produced by parasympathetic ganglia in the small intestine in response to distension
• Motilin is produced by M-cells in the upper small intestine [11][12]

The enzymes produced by the small intestine include lipase for fat digestion, peptidase for peptide breakdown, and sucrase, maltase, and lactase for sucrose, maltose, and lactose breakdown, respectively. Brunner glands, primarily located in the duodenum, produce bicarbonate to neutralize acid.[13]

Within the duodenum, accessory digestive organs such as the liver and the pancreas release digestive secretions. The liver is the largest internal organ and gland in the human body. It has numerous functions, but as an accessory organ of the digestive system, it produces bile, which emulsifies fats and various lipids for optimal digestion. Bile produced in the liver is stored in the gallbladder. The gallbladder contracts to release bile into the duodenum when fat-containing food is present.[14]

The pancreas also has exocrine glands that are essential for digestion. The exocrine glands of the pancreas produce multiple enzyme precursors and enzymes, which include trypsinogen, chymotrypsinogen, and procarboxypeptidase, which are activated by enteropeptidase in the small intestine; active alpha-amylase; lipases and colipase, which act on triglycerides and phospholipids; and several other enzymes like ribonuclease, elastase, and collagenase.[15]

The unabsorbed and undigested food material progresses to the large intestine. At this point, it is called feces. The large intestine is about 6 feet long and comprises the cecum, ascending colon, transverse colon, descending colon, and sigmoid colon. The large intestine absorbs water and electrolytes.[16][17] Also, due to the trillions of microbes that live in the large intestine, these organisms can break down undigested food material. In addition, nutrients such as vitamin K are produced and absorbed in the large intestine.[18] Peristaltic contractions of the large intestine move feces into the rectum. In the rectum, stretch receptors signal for the defecation process to start, which includes a reflexive relaxation of the internal anal sphincter smooth muscle and conscious relaxation of the external anal sphincter skeletal muscle.[19]

Clinical Significance

Gastrointestinal system diseases can affect the mouth to the anal canal and can be caused by a variety of factors. For example, abnormalities of the oral cavity include salivary gland tumors such as pleomorphic adenoma, mucoepidermoid carcinoma, and Warthin tumor, all of which affect proper salivary content and production. The esophagus is subject to a wide range of pathologies: scleroderma, esophageal dysmotility, esophageal strictures, esophagitis, achalasia, and esophageal varices, all of which can affect the movement of food into the stomach.

Further along the gastrointestinal tract, gastritis involves inflammation of the stomach. This condition can vary, depending on the duration of symptoms. Gastritis may have an acute onset caused by NSAIDs or mucosal ischemia. Chronic causes of gastritis are typically due to Helicobacter pylori or autoimmune disease. One such cause of autoimmune disease is pernicious anemia, a condition that prevents either the proper formation of intrinsic factor or its binding to vitamin B12, a nutrient vital for physiologic processes such as DNA and RNA synthesis, hematopoiesis, and neurologic function.[20] Vitamin B12 deficiency can also be attributed to a lack of dietary intake, as the nutrient must be acquired through animal products or fortified food sources.

Diseases of the small and large bowel include celiac disease, tropical sprue, Whipple disease, Crohn disease, and ulcerative colitis, which impact the digestion and absorption of food material. In addition to pathologic conditions, congenital disorders such as Hirschsprung disease, biliary atresia, intestinal atresia, intestinal malrotation, and pyloric stenosis occur during infancy. They may be life-threatening as adequate nutrients cannot be absorbed.

Within the accessory organs of the gastrointestinal tract, there are hereditary hyperbilirubinemia disorders such as Gilbert syndrome, Dubin-Johnson syndrome, and Crigler-Najjar syndrome. The commonality among these conditions is the impairment of normal processes that allow proper uptake, conjugation, and excretion of bilirubin waste products. Other accessory organ pathologies include hemochromatosis, Wilson disease, biliary tract diseases, and pancreatitis. Diseases of the gallbladder prevent proper storage of bile from the liver, leading to malabsorption in the gut. Examples of these conditions include cholelithiasis, choledocholithiasis, and cholecystitis.

These diseases warrant a proper workup, starting with a thorough history and physical examination. Obtaining a history of present illness is essential to the diagnosis of gastrointestinal system disease and clarification of questions regarding the location and duration of the pain, radiation, or changes in intensity, precipitating factors, associated symptoms such as fever, chills, nausea, vomiting, changes in bowel habit, and stool color. Inquiries into any prior episodes of illness or related illnesses, prior surgeries, medication lists, and allergies are crucial.[21]

A proper and thorough physical examination is imperative in the workup of gastrointestinal system diseases. All 4 quadrants of the abdomen must be inspected to appreciate the general abdominal contour.[22] Proper inspection allows for the identification of any surgical scars, bulges, hemangiomas, or dilated veins of a caput medusae when present. Patients may be asked to cough to check for abdominal herniation. After inspection, auscultation is performed to detect any abnormal bowel sounds, rubs, or bruits. It is necessary to consider the anatomical locations of the different abdominal organs, as these determine the sounds heard and the associated pathologies. For example, auscultating the right upper quadrant checks for liver rubs and bowel sounds, while listening to the left upper quadrant examines rubs or bruits within the splenic region. The sounds' pitch, intensity, and duration should also be appreciated during auscultation.

Palpation of the abdomen starts at the right upper quadrant to outline the size of the liver and detect signs of tenderness. The left upper quadrant, periumbilical, left, and right lower quadrants are subsequently palpated to identify any unusual masses or signs of discomfort. The liver and spleen are solid organs that, when percussed, elicit a dull sound. Percussing the abdomen over these organs assesses liver and spleen size and determines whether tenderness is present. Abdominal percussion can also identify abnormal gas collection or ascites. The principle behind this technique is to compare the sounds elicited over a particular area with the normal, expected findings. The rectal exam begins with a thorough inspection of the anal area to identify skin lesions, scars, fistula tracts, or external hemorrhoids.[23] Careful palpation of the anal wall may help identify hypertrophic papillae, inflamed crypts, strictures, and abnormal sphincter tone that might affect normal stool passage.[24]

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Disclosure: Ifeanyichukwu Ogobuiro declares no relevant financial relationships with ineligible companies.

Disclosure: Justin Gonzales declares no relevant financial relationships with ineligible companies.

Disclosure: Karlie Shumway declares no relevant financial relationships with ineligible companies.

Disclosure: Faiz Tuma declares no relevant financial relationships with ineligible companies.