Gastrointestinal Physiology: Organs and Functions

• Gastrointestinal Physiology is the study of the GI organs and their accessory organs
• The GI organs form a long twisting tube from the mouth to the anus
• Accessory organs secrete various substances into the GI lumen to aid in digestive processes

GI and Accessory Organs

• Mouth starts breaking down food
• Salivary glands include the parotid, sublingual, and submandibular glands
• The pharynx is part of the oral cavity that leads to the esophagus
• The esophagus is a long tube allowing food to go from mouth to stomach
• The liver secretes bile needed for digesting fats
• The gallbladder stores bile until needed when eating
• The stomach is a very muscular organ
• The pancreas has both endocrine and exocrine functions
• The large intestine (colon) is the last section of the GI Tract
• The small intestine consists of the duodenum, jejunum, and ileum

Stomach

• Stomach is a muscular organ that churns and breaks down food
• The lower esophageal sphincter (LES) prevents the backflow of stomach contents into the esophagus
• The cardia is the region of the stomach that receives food from the esophagus
• The fundus is the upper portion of the stomach
• The body makes up most of the stomach and is where most muscle movements happen
• The antrum is the lower part of the stomach where most muscle movements occur
• The pylorus is the region leading to the pyloric sphincter.
• The pyloric sphincter acts as a "gate," controlling the release of stomach contents into the small intestine for digestion
• Semiliquid food bolus, called chyme, can enter the duodenum because the sphincter opens slightly

Small Intestine

• The duodenum is about 25 cm long
• The jejunum is about 2.5 m long
• The ileum is about 3.5 m long
• The total length of the small intestine is 6-7 meters
• The small intestine is the initial part of the duodenum, then the jejunum, and lastly the ileum
• The function of the small intestine finishes the process of digestion that started in the mouth and continued in the stomach
• Most of the digestion of food happens in the small intestine
• The small intestine absorbs most of the nutrients
• The small intestine passes the residues on to the large intestine.

Large intestine/Colon

• The main function of the large intestine is to absorb water and electrolytes and store the feces until it is expelled from the body
• The colon is about 1.5 meters long
• Substance from the small intestine is mostly liquid as it enters the large intestine
• The large intestine absorbs a lot of liquid

Sphincters

• Sphincter muscles control the passage of food bolus and fluids from one part of the gut to another
• Sphincters decide when food bolus can move from one area to another and ensure it cannot return to where it came from
• The external anal sphincter and upper esophageal sphincter are under voluntary control and are regulated by the central nervous system
• Sphincter opens under voluntary control
• All other sphincters are smooth muscle and under involuntary control
• These sphincters cannot make conscious decisions

Layers of the GI Tract

• The wall of the GI tract consists of multiple layers of specialised tissue.
• The layers include:
  • Mucosa
  • Submucosa
  • Muscularis Mucosae
  • Epithelium
  • Lamina Propria
  • Lumen
• A food bolus resides in the lumen
• The stomach and small intestine produce folds that increase the absorptive surface area of the mucosa
• The mucosa is composed of the epithelium, lamina propria and muscularis mucosae
• Blood and lymphatic vessels in the lamina propria absorb the end products of digestion.
• The submucosa is a connective tissue layer containing large blood vessels and an extensive lymphatic system
• Epithelial cells play a role in nutrient absorption and the secretion of hormones and mucus
• Muscular mucosae, a thin muscle layer generates local movements.
• The circular and longitudinal muscle layers work together to coordinate the contractions necessary for moving and mixing the food bolus along the gut
• Sphincters are formed from the circular muscle layer
• The enteric nervous system (ENS) is comprised of two nerve layers, or intrinsic nervous system that controls locally what happens
• These layers are: the submucosal and the myenteric plexus
• The serosa covers the muscle layers

Intestinal Mucosa

• Intestinal mucosa is arranged into villi and crypts and they both have absorptive epithelial cells and cells that are important for secretion
• finger-like extensions (villi) increase surface area
• the epithelial cells are made at the bottom of the crypt and then travel up

Gasterointestinal Function Control

• There is neural control via the central control, parasympathetic and sympathetic autonomic nervous systems
• Intrinsic control by the enteric nervous system (ENS) is local
• Endocrine control is when enteroendocrine cells (EECs) secrete peptides that travel via blood stream to remote target organs, or travel long distances
• There is also Paracrine control, where EECs secrete peptides that act on target cells nearby
• The enteric nervous system (ENS) is comprised of two nerve layers, or intrinsic nervous system that controls locally what happens
• There is the myenteric plexus and the submucosal plexus
• They communicate with each other and with target organs
• Extrinsic innervation is mainly by the autonomic nervous system
• Intrinsic innervation is by the enteric nervous system (ENS)
• The sensory nervous system (neurons) are extremely important in the GI system

Nerves controlling the GI System

• The neural control of the Gl system involves ENS, ANS and CNS
• The enteric nervous system (ENS), intrinsic to the gut, regulates Gl movements and secretions
• Comprising the myenteric and submucosal plexi, it communicates with end organs (smooth muscles, blood vessels, glands) coordinating essential gut functions.
• The parasympathetic branch of ANS is active during rest and digestion, innervating ENS neurons crucial for digestive functions.
• The sympathetic branch of the ANS inhibits gut activity via the ENS
• The sympathetic branch also has a slight direct inhibitory effect on intestinal smooth muscles and glands.
• Sensory neurons in the gut wall detect stimuli such as distention, chemicals, irritation, and pain.
• Sensory neurons send afferent fibers to the ENS and ANS, with some sensory fibers projecting to the dorsal root ganglia (DRG) of the spinal cord
• Sensory afferents elicit local reflexes within the gut wall via the ENS and trigger long reflexes relayed to the gut via the ANS from the higher centers in the CNS.
• The ENS is often called the "little brain"
• The ENS consists of 400-600 million neurons, and its diversity of neurons, glial cells and neurotransmitters is comparable to the CNS
• The extrinsic innervation also integrates well with the enteric nervous system and relates to the body
• Most of the extrinsic innervation is provided by afferent sensory neurons
• Preganglionic cholinergic fibers synapse on nicotinic ACh receptors on target tissues.
• Postganglionic fibers release norepinephrine (NE) and act on adrenergic receptors.

EECs

• Enteroendocrine cells (EECs) secrete peptides that travel far
• EECs are electrically excitable cells that detect sensory stimuli
• There are different types of peptides in the gut
• Peptides are always released into the blood (never the lumen side)
• Peptides are derived from amino acids
• They always function in the human body
• Peptides always act as hormones in some organ

Hormones

• Gastrin is secreted upon the sight, thought or smell of food, as well as when the food reaches the stomach due to sensing protein
• When stomach senses protein and food it release Gastrin
• The thought of, seeing and smelling food causes Gastrin release
• Secreted from G-Cells
• A major function of somatostatin is to make stomach contents acidic, and too acidic leads to appetite inhibition
• Gastrin/CCK² receptors are found in parietal and ECL cells
• There is 5-10 times more gastrin compared to CCK in the Gl system, so gastrin bind more to CCK² receptors

Cholecystokinin (CCK)

• Cholecystokinin (CCK) is released when small intestine senses fatty acids, monoglycerides, peptides, and amino acids
• Secreted from I-Cells
• CCK1 receptors bind to CCK
• Can bind to Gastrin/CCK2 receptors
• Binds specifically to CCK and mediates typical actions in the gut; gastrin cannot bind there

Secretin

• When duodenum senses acidity the the S-Cell releases secretin
• This is when contents of stomach enter the duodenum
• Secretin can be derived from the small intestine primarily in the duodenum
• Homologous to glucagon

Incretins: GIP & GLP-1

• GLP-1 secreting L-cells are in the jejunum, ileum and in the colon
• GIP secreting K cells are in duodenum and jejunum
• Colonic secretion of GLP-1 occurs when secondary metabolites appear, hours after ingestion of the meal.
• GIP and GLP-1 decreases blood glucose level in the blood
• GLP-1 also signals satiety to the CNS and slows gastric emptying
• Some of these drugs (ozempic) are also employed in the treatment of obesity, as it makes people feel full

Food Intake

• Food intake is controlled by several different peptides.
• NPY = neuropeptide Y, AgRP = agouti related peptide, POMC = propiomelanocortin and CART = cocaine and amphetamine-regulated transcript
• Food intake is modulated by higher brain areas, including those that signal reward and are involved in addictive behaviors
• Ghrelin stimulates appetite while Leptin inhibits it

Plasma levels of Ghrelin

• Plasma levels of Ghrelin are highest just before each daily meal.

Motilin

• Motilin is secreted during the interdigestive period mainly by M-cells of the duodenum and jejunum
• CNS Increased hunger appetite increasing hormone
• Motilin can stimulate the migrating myoelectric complex (MMC) (which is responsible for stomach movements during digestion), gastric emptying, and small intestine motility
• But it can also inhibit gastric accommodation doesn't allow anymore food
• Motilin regulates to the gall bladder to stimulate contraction and emptying
• Stimulates the pancreas to stimulate insulin secretion

Paracrine Agents

• These agents can inhibit gastric acid secretion, stimulate gastric acid secretion, and regulate Gl motility, secretion, involved in nausea