Physiology, Gastrointestinal

Issues of Concern

The GI system is complex, and the amount of material that could be covered is substantial. Therefore, this article serves as an overview of GI tract physiology, with reference links diving deeper into complex topics.

Cellular Level

There are four histologic layers of the GI 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, which release Gi 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 GI tract. The submucosal (Meissner) plexus is found in this layer.

Muscularis Externa 

The muscularis externa comprises two major smooth muscle layers: an inner circular and an outer longitudinal muscular layer. Between these two layers is where 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 Adventitia

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 aids in reducing friction during movement. The serosa covers intraperitoneal organs, while the adventitia covers retroperitoneal organs and functions to hold structures together instead of reducing friction between them.

Development

The digestive tube begins to form during the third week of gestation. During this time, gastrulation occurs, and three germ layers (ectoderm, mesoderm, and endoderm) are formed.

The endoderm forms the epithelial lining of the GI 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 (ENS); the ENS contains the neurons of the GI 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 four main functions. First, it provides sensory analysis of food material before swallowing and mechanical processing via the action of 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 are 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 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 three 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 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 of 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 muscle, 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 the actions of stomach acids and enzymes. The secretion of intrinsic factor produced by the stomach helps appropriately absorb vitamin B12.[6] The ability of the stomach to store food stems from its compliance and ability 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, giving it the ultimate ability to hold on to a large amount of food.

The ability of the stomach to mechanically break down food materials is due to its sophisticated muscular dimensions. The stomach has three muscular layers: an inner oblique layer, a middle circular layer, and an external longitudinal layer. The contraction and relaxation of these three muscular layers of the stomach assist in the mixing and churning activities essential in the formation of chyme. Then the chemical breakdown of food material in the stomach is propagated by the gastric glands, produced majorly 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 to 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 to 2 to become pepsin. Pepsin is a protein-digesting enzyme. The foveolar and mucous neck cells produce mucous, protecting the gastric epithelium from acidic corrosion.[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 three 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 occur. The ileum also has digestion and absorption 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.[11][12]

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

The enzymes produced by the small intestine include lipase for fats digestion, peptidase for peptide breakdown, and sucrase, maltase, and lactase for sucrose, maltose, and lactose breakdown, respectively. Brunner glands, primarily found in the duodenum, produce bicarbonate for acid neutralization.[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 the food digestion process. 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 six 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] The peristaltic movement of the large intestine moves the 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 anywhere from the mouth to the anal canal and can be caused by any number of things. 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 are diseases that 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 preventing either the proper formation of intrinsic factor or its binding to vitamin B12, a nutrient vital in 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 supplemented food sources.

Diseases of the small and large bowel include celiac disease, tropical sprue, Whipple disease, Crohn disease, and ulcerative colitis, which impact digestion and absorption of food material. In addition to pathologic conditions, congenital disorders such as Hirschprung 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, Dublin-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 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 habitus, and stool color. Inquiries on any previous episodes of illness or related illnesses and 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 four quadrants of the abdomen must be inspected to appreciate the general abdominal contour.[22] Proper inspection allows for identifying 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 location of the different abdominal organs, as this determines the sounds heard and the pathologies that correlate. 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 in the areas overlying these organs serves the purpose of assessing the size of the liver and spleen and determining whether tenderness is present. Percussion of the abdomen can also identify any 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 thoroughly inspecting the anal area to identify skin lesions, scars, fistula tracts, or external hemorrhoids.[23] Careful palpation of the anal wall may help identify any hypertrophic papillae, inflamed crypts, strictures, and abnormal sphincter tone that might affect the normal passage of stool.[24]