Gastrointestinal System Flashcards
What are the functions of the gastrointestinal tract (GIT)
Transfers digested organic nutrients, minerals, and water from the external environment to internal environment. Plays a role in digestion and absorption.
What occurs during digestion in the gastrointestinal tract
Chemical alteration of food into absorbable molecules. GI motility, pH changes, biological detergents, and enzymes.
What occurs during absorption of the gastrointestinal tract
Movement of digested food from the intestine into the blood or lymphatic system.
What is excretion of the gastrointestinal tract
Non-absorbable components of food, bacteria, intestinal cells, hydrophobic molecules (drugs, cholesterol, and steroids).
How does host defense occur for the gastrointestinal system
GIT is continuous with the exterior of the body. It is a potential portal for harmful substances and microorganisms. We develop a highly developed immune system due to this.
What are the components of the gastrointestinal tract
Mouth, Pharynx, Esophagus, Stomach, Small intestine (Duodenum, Jejunum, Ileum), and the Large Intestine
What are the accessory organs are made of the gastrointestinal system
Pancreas, Liver, and Gall Bladder.
What is the structure of the GIT
Long muscular tube stretching from mouth to anus. It’s composition from mid-esophagus to anus is very similar with some exceptions.
What are the layers of the mucosa
Epithelial layer Lamina propria Muscularis mucosa Submucosa Muscularis externa Serosa
What is the epithelial layer of the mucosa
Epithelium is the layer of cells that lines all body cavities and surfaces. “Polarized” meaning that it is different at one surface compared to the other. Basolateral and apical arrangement. Different transport proteins at the apical structure compared to basolateral. Tight junctions confine transport proteins to specific membrane regions. Provides selective uptake of nutrients, electrolytes, and water. Prevents passage of harmful substances. Surface area is amplified by villi and crypts (+ microvilli). Stem cells in crypts divide and daughter cells migrate upwards toward the villous.
What is the lamina propria layer of the mucosa
Connective tissue, small blood vessels, nerve fibers, lymphatic vessels, and immune and inflammatory cells.
What is the muscularis mucosa layer
Thin layer of smooth muscle. Not involved in the contraction of the GIT. May be important in villi movement.
What is the submucosa layer of the mucosa
Plexus of nerve cell bodies. Relays information to and away from the mucosa. Also composed of connective tissue, blood, and lymphatic vessels.
What is the muscularis externa layer of mucosa
Thick inner layer of circular muscle which has fibers oriented to cause narrowing of lumen. Myenteric nerve plexus which has a network of nerve cells, which regulate muscle function. Thinner outer layer of longitudinal muscle which has fibers oriented to shorten muscle.
What is the serosa layer of the mucosa
Connective tissue, encases intestine and forms connection point to the abdominal wall.
What is the paracellular pathway
It is limited by the tight junction seal and water and small ions can diffuse through it.
What is the transcellular pathway.
It is a two-step process that requires a transport protein on the apical and basolateral surface of the cell.
How is blood supplied to the GIT
It is critical for carrying away water soluble absorbed nutrients for usage at other sites in the body. Blood perfuses intestine and then flows to the liver via the portal vein.
What is portal circulation
The portal vein drains blood from the digestive tract and empties directly into the liver. It is a circulation of nutrient-rich blood between the gut and the liver. This allows the liver to remove harmful substances and process nutrients.
Why is the liver an unusual organ
Liver is an unusual organ because it receives blood from both venous (portal) and arterial circulation. Liver receives less oxygenated blood, more nutrient rich blood than other organs.
How is the gastrointestinal processes regulated
Governed by the volume and composition of lumen
What are the reflexes of the GI tract initiated by
Distension of wall by volume of luminal contents, osmolarity of contents, pH of contents, and concentrations of specific digestion contents such as (monosaccharides, fatty acids, peptides, and amino acids).
What are the regulations of the GI processes propagated by
Mechanoreceptors: Activated by mechanical stimuli such as pressure and stretch
Osmoreceptors: Activated by changes in osmolarity
Chemoreceptors: Activated by the binding of specific chemicals.
What is the intrinsic neural regulation of the GI Processes
Enteric nervous system. Controls the activity of the secretomotor neurons; such as motility and secretory function. Contained completely within the walls of the GIT. Dense and complex network of neurons. Brain of the gut and can function independently of the CNS.
What are the nerve networks the intrinsic neural regulation
Myenteric plexus influences smooth muscle
Submucosal plexus influences secretion
What does the extrinsic neuronal regulation of the GI processes
There is parasympathetic and sympathetic processes
What does the extrinsic neuronal regulation of GI processes influences
Hunger, Sight/smell of food, and emotional state.
What is the parasympathetic reaction of the mouth
Stimulates flow of saliva
What is the parasympathetic reaction of the stomach
Stimulates peristalsis and secretion
What is the parasympathetic reaction of the liver
Stimulates releases of bile
What is the sympathetic reaction of the mouth
Stimulates flow of saliva
What is the sympathetic reaction of the stomach
Inhibits peristalsis and secretion
What is the sympathetic reaction of the liver
Conversion of glycogen to glucose
What are endocrine chemical messengers in the GI tract
Endocrines are hormone-secreting gland cell. They release hormones in the blood vessels. They target cells in one or more distant places in one body.
What are neurocrine chemical messengers in the GI tract
It impacts the nerve cell, releases a neurotransmitters. Neuron or effector cell near site of neurotransmitter release.
What are paracrine chemical messengers in the GI tract
Impacts the local cell. Releases a paracrine substance. Target cells near site of release of paracrine substance.
What are autocrine chemical messengers in the GI tract
Impacts the local cell. Releases the autocrine substances. Autocrine substances acts on the same cell that secreted the substance.
How do endocrine chemical messengers control GI activity
Chemical messenger passes from cell which produced it into blood and is carried blood to it (relatively distant) target
How do neurocrine chemical messengers control GI activity
Chemical messenger is released from a nerve, travels across a synapse and acts on a post-synaptic cell.
How do paracrine chemical messengers control the GI activity
Chemical messenger diffuses through intestinal fluid to nearby cells.
How do autocrine chemical messengers control GI activity
Chemical messenger acts on the cell which produced it.
What is the hormonal control of the GI activity
Endocrine cells are scattered throughout the epithelium of the stomach and small intestine. One surface each endocrine cell exposed to the GI lumen. The chemical substances in lumen stimulate cell to release hormones across opposite surface of the cell into blood vessels in lamina propria. Hormones travel through blood to target cells.
What are the best understood GI hormones
Secretin, Cholecystokinin (CCK), Gastrin, and Glucose-dependent insulinotropic peptide (GIP). Each participates in a feedback control system that regulates some aspect of the GI lumen. Most GI hormones affect more than one type of target cell.
What does Gastrin do
Major release site: Stomach antrum (G cells)
Major stimuli for release: Peptides/amino acids in stomach, parasympathetic nerves.
Major actions: Increase in HCl, and an increase in motility (stomach, ileum, and large intestine)
What does Secretin do
Major release site: Small intestine (S cells)
Major stimuli for release: Acid in small intestines (pH < 4.5)
Major actions: Decrease in HCl, decrease in stomach motility, and an increase in HCO3-/H2O from pancreas and in bile.
What does Cholecystokinin (CCK) do
Major release site: Small intestine (I cells)
Major stimuli for release: Digested fat/protein in small intestine
Major actions: Decrease in HCl, decrease in stomach motility, and an increase in enzymes from the pancreas and bile expulsion.
What does Glucose-dependent insulinotropic peptide (GIP) do
Major release site: Small intestine (K cells)
Major stimuli for release: Glucose or fat in the small intestine
Major actions: Increase in insulin
What is intestinal motility
Contraction and relaxation of the two outer smooth muscle layers of the GIT allows the movement of contents from one site to another. Two forms peristalsis and segmentation
What is peristalsis (propulsion)
Circular muscle contracts on the oral site of a bolus of food (longitudinal layer relaxes). Circular muscle contracts and moves toward the anus, propelling the contents of the lumen in that direction, as the ring moves, the circular muscle on the other side of the distended area relaxes (longitudinal muscle contracts), facilitating smooth passage of the bolus.
What is segmentation (mixing)
Contraction and relaxation of intestinal segments with little net movement of contents towards the large intestine. Mostly occurs in the small intestine. Allows mixing of contents with digestive enzymes. Slows transit time to allow absorption of nutrients and water.
What is the basic electrical rhythm of the GIT
GIT has pacemaker cells throughout the smooth muscle cells. Constantly undergoing spontaneous depolarization-repolarization cycles (slow waves). These slow waves are the basic electrical rhythm
What are the slow waves of the basic electrical rhythm
Slow waves propagated through the circular and longitudinal muscle layer through gap junctions. In the absence of neural/hormonal input spontaneous slow waves don’t result in significant contractions. Excitatory hormones/neurotransmitters further depolarize the membrane and bring it close to threshold.
How does the force and frequency of contractions are seen in the GI tract
The number of action potentials fired proportional to force of contraction. Frequency of contraction maintained by the basic electrical rhythm. Force of contraction mediated by neuronal and hormonal input.
What are the phases of the gastrointestinal control
- Cephalic (head)
- Gastric (stomach)
- Intestinal
What is the cephalic phase of the gastrointestinal control
Receptors in the heads are stimulated by sight, smell, taste, chewing of food, and emotional state. The parasympathetic fibers activate neurons int he GI nerve plexi.
What is the gastric phase of the gastrointestinal control
Receptors in the stomach stimulated by distension, acidity, amino acids, and peptides. Short and long neural reflexes mediate the response (gastrin and acetylcholine).
What is the intestinal phase of gastrointestinal phase
Receptors in intestine stimulated by distension, acidity, osmolarity, and digestive products. Mediated by short and long neural reflexes by hormones secretin, cholecystokinin, and glucose-dependent insulinotropic peptide (GIP). All of these are secreted by endocrine cells in the small intestine.
What controls food intake
Hypothalamus which contains the feeding and satiety centers.
What is the feeding center
Found in the hypothalamus, found in the lateral region. Activation of this region increase hunger. Animals with lesions in this area become anorexic and lose weight.
What is the satiety center
Found in the hypothalamus in the ventromedial region. Activation of this region makes you feel full. Animals with lesions in this area overeat and become obsese.
What are orexigenic factors
These increase intake. Neuropeptide Y, NPY will stimulate hunger. Ghrelin which synthesizes and releases from endocrine cells in the stomach during fasting, and stimulates the release of NPY and other neuropeptides in hypothalamus feeding center.
What are the anorexigenic factors
They decrease intake. Leptin (from adipose), insulin (from pancreas), peptide YY (from intestines), and melanocortin (from hypothalamus)
How is Water Intake regulated
- Increased plasma osmolarity
- Decrease plasma volume
- Dry mouth and throat will stimulate thirst
- Prevention of over-hydration
How does an increased plasma osmolarity impact water intake
Most important under physiological conditions. Osmoreceptors in thirst center within the hypothalamus. Vasopressin (antidiuretic hormone is released) causing a conservation of water at the kidneys
How can a decrease in plasma volume impact water intake
Stimulation of baroreceptors in cardiovascular system. Baroreceptors in kidney afferent arteries leading to activation of renin angiotensin system. Result is production of angiotension 2 which as a direct effect on the hypothalamus to increase thirst.
How can prevention of over-hydration impact water intake
Person stops drinking well before water is absorbed by GIT. Probably mediated by stimulus from mouth, throat, and GIT.
What are the three main salivary glands
Parotid glands which produce a serous secretion
Submandibular glands which produce a serous/mucous secretion
Sublingual glands which produce a mucous secretion
What composes Saliva
Water (96-99.5%, hypotonic, and slightly alkaline)
Electrolytes (Relatively rich in K+ and HCO3-, and relatively poor in Na+ and Cl-)
Digestive enzymes (amylase, lipase)
Glycoproteins (Mucin [mucin + water = mucuous]
Other components (Anti-microbial factors like lysozyme, lactoferrin, and others)
What are the functions of saliva
Moistens and lubricates food. Initiates digestion with amylase and lingual lipase. Dissolves a small amount of food to allow diffusion to taste buds which affects appetites and food intake. Antibacterial actions which prevents microbial colonization. Aids in speech. Buffering action which contains HCO3- which helps to neutralize acids.
How do acinar cells form saliva
With water, electrolytes, and proteins. The proteins are released by exocytosis. Cl-, bicarbonate and potassium ions are actively secreted. Na+ and H2O follow paracellularly via the (leaky) tight junctions. Initial secretion is isotonic (ionic composition comparable to plasma) due to leakiness of acinar cell layer. Myoepithelial cells contract and expel formed saliva from acinus into the duct.
How do ductal cells form saliva.
Ductal cells modify the initial saliva to a hypotonic and alkaline state. Net loss of Na+ and Cl- (active reabsorption). Addition of K+ and HCO3- (active secretion) - to a lesser extent. Duct cells are tightly joined and impermeable to H2O.
What is the role of saliva in digestion
Starch digestion is initiated in the mouth by amylase. Inhibited at acidic pH in stomach. 95% of carbohydrates digested in the small intestine by pancreatic amylase. Plant starch made up of glucose polymers-amylose and amylopectin. Lingual lipase causes the acid to stable and therefore active in stomach. Overall amylase and lingual lipase are minor pathways for digestion which may be important during pathological conditions and neonates.
What is salivary pathophysiology
Variety of conditions where salivary secretion is impaired through congenitally, autoimmune processes, side effects of drugs, and radiation treatments.
What are some consequences of salivary pathophysiology
Dry mouth, decrease oral pH (tooth decay, esophageal erosions), difficulty in lubricating and swallowing food (poor nutrition).
How to treat salivary pathophysiology
Frequent sips of water and fluoride
What is swallowing
Complex reflex initiated by pressure receptors in the walls of the pharynx. Stimulated by food/liquid entering the pharynx. Receptors send signals to the swallowing center in the brainstem. In turn signals to muscles in the: pharynx - throat passage common to food and air, esophagus, and respiratory muscles.
What is the larynx
Voice box, located between the pharynx and trachea.
What is the glottis
Area around the vocal cords - where air travels through
What is the epiglottis
Tissue flap that covers larynx and trachea during swallowing
What is the steps of swallowing
- Tongue pushes food bolus to the back of the pharynx
- Soft palate elevates to prevent food from entering the nasal passages. Impulses from the swallowing center. Inhibits respiration, raises the larynx and closes the glottis.
- Epiglottis covers the glottis to prevent food or liquid entering trachea
- Food descends into the esophagus.
What is the esophagus
Transfers food from mouth to stomach. 18-25 cm long tube. Skeletal muscle surrounds the upper third, smooth muscles surround the lower two-thirds. Food passes very rapidly, no absorption, mucous glands for lubrication. Exposed to rough/abrasive food contents but there is specialized epithelium to protect the esophagus.
What are the esophageal sphincters
Upper esophageal sphincter: Ring of skeletal muscle just below the pharynx
Lower esophageal sphincter: Ring of smooth muscle at the stomach.
The sphincters are closed when swallowing, vomiting, and burping
What are the esophageal phase of swallowing
- Relaxation of the upper esophageal sphincter
- Peristaltic waves move food bolus down the esophagus (one wave takes 5-9 seconds from the top to the stomach).
- Lower sphincter opens and allows food to pass into stomach
What happens when the upper esophageal sphincter relaxes
Food passes through, sphincter closes, glottis opens breathing resumes.
What happens when the lower sphincter opens and food enters the stomach
Once the food passes the sphincter the sphincter closes
What is the main driving force of swallowing
Peristalsis is along with gravity that assist but it is not necessary because you can swallow in zero gravity and when hanging upside down.
What is heart burn
The lower esophageal sphincter prevents gastric contents from reaching the esophagus.
What happens when acid reaches the esophagus
Stimulates peristalsis, increases salivary secretion, and results in neutralization and clearance.
How can heart burn occur
Due to an insufficient sphincter, after a big meal, and during pregnancy.
What is the stomach
Muscular saclike organ located between the esophagus and the small intestine
What are the functions of the stomach
Storage of food. Mechanical breakdown of food. Chemical breakdown of food. Reduces food to fragments of proteins, polysaccharides, droplets of fat, salt, and water “chyme.” Control the rate at which food enters the small intestine. Secretes “intrinsic factor” critical for absorption of Vitamin B12 in the ileum. Very little absorption across the stomach
How is food chemically broken down in the stomach
The stomach secretes pepsinogen which converts to pepsin which is the protein digesting enzyme. The stomach also secretes HCl for dissolving food, partially digesting macromolecules in food and sterilization of food.
Why is the intrinsic factor important in the stomach
Vitamin B12 is required for normal red blood cell formation. Lack of intrinsic factor results in pernicious anemia which is a red blood cell deficiency.
What are the components of the stomach
Fundus, Body and Antrum
What do the fundus and body do in the stomach
They are the thinner layers of smooth muscle and they secrete mucous, pepsinogen, and HCl
What does the antrum do in the stomach
It is the thicker smooth muscle layer and it secretes mucous, pepsinogen, and gastrin
What are the major exocrine secretions of the stomach
Substances secreted into ducts then on to an epithelial surface without passing into blood. They are mucuous, HCl and pepsinogen
What is the mucous secretion of the stomach
It is the protective coating over stomach epithelium to avoid “self-digesting”
What is the HCl secretion of the stomach
Hydrolysis of proteins
What is the Pepsinogen secretion of the stomach
Digestion of proteins
What are the minor secretions of the stomach
Intrinsic factor, gastrin, histamine, and somatostatin
What is the intrinsic factor secretion of the stomach
Responsible for Vitamin B12 absorption
What is the gastrin secretion of the stomach
Endocrine and it stimulates HCl production and stomach motility
What is the histamine secretion of the stomach
Paracrine, stimulates HCl production
What is the somatostatin secretion of the stomach
Paracrine, and it inhibts HCl production
What are the different types of cells in the stomach
Chief Cells Enteroendocrine Cells Enterochromaffin-like Cells D-Cells Parietal Cell
What are chief cells in the stomach
Gastric glands in all regions of the stomach. They secrete pepsinogen which is an inactive precursor to pepsin (zymogen), pepsinogen cleaved by acid to pepsin, and pepsin accelerates protein digestion
What are enteroendocrine cells in the stomach
Gastric glands in the antrum. Also known as G-cell. Secretes gastrin which is responsible for stimulating HCl production by parietal cell and stimulating GI motility.
What are enterochromaffin-like cells in the stomach
Gastric glands in all regions (more in antrum). It secretes histamine and stimulates HCl release.
What are D-cells in the stomach
Gastric glands in all regions (more in antrum). Secretes somatostatin and it has negative regulation of HCl secretion
What is a parietal cell in the stomach
Found in gastric glands contained in the fundus/body regions. Also known as an oxyntic cell. Secretes HCl and intrinsic factors. Canaliculi increase the surface area of the cells and maximize secretion to the stomach lumen.
What is the role of the parietal cell in the stomach
Responsible for acid secretion, acid secretion requires energy-lots of mitochondria, and actively secreting cell has better defined “canaliculus”
What ensures the acidification of the stomach lumen
- H+/K+ ATPase
- Carbonic anhydrase (CA)
- Cl-/HCO3- exchanger - responsible for secondary active transport
- K+ channels
- Cl- channels
What is the role of H+/K+ ATPase in the acidification of the stomach lumen
It is in the luminal membrane, it pumps H+ into the lumen exchange for K+ into the cell. It did this through active transport and it was electroneutral.
What is the role of carbonic anhydrase in the acidification of the lumen
Catalyses the formation of H2CO3 from H2O and CO2. H2CO3 dissociates into H+ (for secretion into lumen) and HCO3-
What is the role of the Cl-/HCO3- exchanger in the acidification of the stomach lumen
Excess HO- is effluxed from the cell as HCO3- in exchange for Cl-. This is a critical step (in conjunction with carbonic anhydrase) for maintenance of neutral cellular pH
What is the role of K+ channels in the acidification of the stomach lumen
K+ is recycled back into the stomach lumen. This is done through diffusion through a channel and there is a loss of positive charge (which is compensated by Cl- secretion)
What is the role of the Cl- channels of the acidification of the stomach lumen
Cl- leaks back into the stomach lumen. There is diffusion through the channel and it compensates for loss of positive charge through K+ channels.
What are the four chemical messengers that regulate acid secretion of the parietal cell
Gastrin (gastric hormone)
Acetylcholine (neurotransmitter)
Histamine (paracrine)
Somatostatin (paracrine) - the only messenger that inhibits the release of HCl, gastrin, and histamine.
How is pepsinogen secreted by chief cells
Stimulation by enteric nervous system and there is parallels release of HCl.
What is advantage of inactive precursor secretion
Makes sure that we don’t go through with self-digestion. Pepsin is active only at low pH - irreversibly inactivated when it enters the small intestine.
What aer the Phases of the Gastric Secretion
- Cephalic Phase - Anticipatory, excitatory, and mainly via the vagus nerve.
- Gastric Phase - Major phase, excitatory, and mainly via gastrin
- Intestinal phase - Mainly inhibitory, due to the presence of acid, fat, digestion productions and hypertonic solutions in the duodenum
How does acetylcholine regulate gastric secretions
Acetylcholine also increases acid secretion by the parietal cell by stimulating the release of gastrin from G-cells, and stimulating the release of histamine from enterochromaffin like cells, and inhibiting somatostatin release from D-cells.
How does somatostain regulate gastric secretion
Somatostatin inhibits acid secretion by parietal cell.
How does gastrin regulate gastric secretion
Gastrin also increases acid secretion by the parietal cell by stimulating histamine release
What happens when acid secretion happens at a high rate
Parasympathetic input will be reduced during the cephalic phase. Negative feedback occurs for gastrin production and the acid inhibits release. Somatostatin release increases due to reduced parasympathetic inhibition of D-cell and direction stimulation of somatostatin release by acid. Somatostatin then directly inhibits acid secretion from parietal cell, inhibits histamine release from enterochromaffin-like cells, and inhibits gastrin release from G-cell.
How is the stomach flexible
Empty stomach is small (50 mL) diameter larger than the small intestine. Consumption of meal will lead to smooth muscle relexation which will lead to stomach increasing to about 1.5 L without increasing pressure.
How does gastric motility occur
Food stimulates peristaltic waves whcih are weak contraction in the body of the stomach. This causes a powerful contraction in the antrum which mixes luminal contents and causes the closure of the pyloric sphincter
What happens when the pyloric sphincter is closed in the stomach
Small amounts of stomach contents released to the duodenum, and most antral contents are forced backward towards the body of the stomach resulting in mixing of contents with enzymes and acid.
What is the electrical basis of stomach motility
The stomach has pacemaker cells in the smooth muscle layers which causes spontaneous slow waves of depolarization and replorization. Excitatory hormones and neurotransmitters further depolarize and determine the strength of a stomach contraction
What can trigger the vomiting center in the medulla
Psychogenic factors such as sights and smells
GIT disturbances such as infection, distension, and obstruction
Motion sickness or an inner ear infection
Alcohol and toxins which trigger chemoreceptors in the GIT or brain
Pressure on the central nervous system
What happens when the vomiting center is triggered in the medulla.
- Nausa, Salivation, and breath held in mid-inspiration
- Glottis closes off trachea
- Lower esophageal sphincter and esophagus relaxes
- Diaphgram and abdominal muscles contract
- Reverse peristalsis moves upper intestinal contents into the stomach
- Stomach contents move up through esophagus and out through the mouth
- The soft palate is raised to avoid vomit coming out of the nose
What are the benefits of vomitting
Removal of harmful substances prior to absorption such as bacteria and toxins. Nausea and feeling bad should prevent individual from consuming noxious substances again.
What are the consequences of vomiting
Dehydration, loss of salts (electrolyte imbalance), metabolic alkalosis due to loss of H+, and acid erosion of tooth enamel.
What are ulcers
A damaged/eroded area of GIT mucosa, usually in acidic regions. This can occur in the esophagus, stomach, or most commonly in the duodenum.
What can cause ulcers
Imbalance between “agressive” factors (acid, pepsin), and “protective” factors (mucus, HCO3-)
Helicobacter pylori infection - causes chronic inflammation and erosion
NSAIDS (aspirin, ibuprofen) - decreases prostaglandin production
Smoking
Excessive alcohol
Stress
Gastrinomas
How can you treat ulcers
Antibiotics
H+/K+ ATPase inhibitor
Histamine (H2) antagonist
Prostaglandin type drugs
What is gastric bypass surgery
In extremely obese patients a surgery will be performed that results in the bypassing of the stomach and rooting the food directly to the small intestine.
What are the problems that can occur with gastric bypass surgery
Lack of intrinsic factor release, less acid treatment with food, and difficulty regulating the amount of food reaching the small intestine
How do patients ensure that gastric bypass surgery is successful
Vitamin B12 injections and eating smaller meals.
What does the exocrine pancreas do
Produces secretions that go into gut. Source for most enzymes required for meal digestion such as carbohydrates, protein, fat, and nucleic acid. Enzymes are produced in excess and this is notably because problems with digestion and absorption will occur if this function falls below 10%. Critical for secreting HCO3- into the duodenum for the neutralization of stomach acid which is critical for enzyme function
What does the endocrine pancres do
It is non-digestive and produces hormones that regulate the entire body. It’s primary hormone release is insulin
What is the anatomy of the exocrine pancreas
Secretion of substances into ducts that drain onto an epithelial surface
What is the anatomy of the endocrine pancreas
Ductless gland, secretion occurs across epithelial basolateral surface for diffusion into blood.
What are the pancreatic ducts
Very similar to salivary glands, they are acinar cells that produce and secrete digestive enzymes through exocytosis. The duct cells secrete H2O and HCO3-.
What are pancreatic juices
Isotonic, alkaline, and 1-2 L made per day. It contains electrolytes and digestive enzymes.
What are the electrolytes in pancreatic juices
High HCO3-, low Cl-.
HCO3- and H2O was secreted mainly but the duct cells. HCO3- neutralizes gastric acid in the duodenum
What are the digestive enzymes responsible for in pancreatic juices
Essential for digestion of proteins, carbohydrates, fats, and nucleic acids. Secreted by acinar cells. Proteolytic enzymes stored and secreted in inactive forms; activation occurs in the duodenum,
How is HCO3- made in the pancreatic duct cells
- Chloride channel (CFTR) opens
- Cl- in lumen exchanged for HCO3- in cell
- H2O and Na+ follow paracellularly in response to electrochemical gradient across epithelium
- Neutral pH of cytosol is maintained by exchange of H+ (exported from cell) for Na+ (imported) - this is used in combination with carbonic anhydrase
What happens to the alkaline and acid tides after you consume a big meal
Parietal cell in the stomach are producing lots of acid, large amount of HCO3- pumped across the basolateral surface into blood stream. This referred to as alkaline tide.
Duct cells in pancreas are producing and secreting HCO3-, large amounts of H+ being pumped across the basolater surface into blood stream. This is referred to as acid tide.
HCO3- from stomach and H+ from pancreas eventually meet up in the portal vein
What is the digestive function of the pancreas
Source for most enzymes required for meal digestion, acinar cells synthesize and pack pro-enzymes into zymogen granules that are stored at the apical pore of the cell, and appropriate neurohormonal input results in their exocytosis into the lumen of the duct.
What would happen if we didn’t have a pancreas
Starvation would occur without the pancreas
What do amylolytic enzymes do
Digest starches into sugars
What do lipases do
Digest triglycerides into free fatty acids and monoglycerides
What do nucleases do
Digest nucleic acids into free molecules
How are digestive enzymes secreted from the pancreas
Most enzymes secreted as inactive forms that are activated in the duodenum. Enterokinase-enzyme embedded in the luminal membrane of the duodenum. It cleaves trypsinogen to trypsin. Trypsin is a protease and activates other proteases.
How is autodigestion prevented
Storage of digestive enzymes as inactive proforms and these can’t normally be activated unless they reach the intestine. Pancreas also secretes a variety of trypsin inhibitors to antagonize any prematurely activated trypsin. Trypsin can degrade itself if activated prior to reaching the intestine.
How is the pancreas related to cystic fibrosis
The Cl- channel involved in HCO3- secretion in the pancreas is the channel that is mutated in the disease cystic fibrosis. CF patients can suffer from “pancreatic insufficiency”
What is “pancreatic insufficiency” in cystic fibrosis
Still produce all the digestive enzymes. HCO3- and H2O secretion is minimal, and enzymes do not get flushed from ducts and therefore do not reach the intestine. Retained proteolytic enzymes can result in pancreatic autodigestion. Must receive supplements of digestive enzymes and antacids to allow for adequate nutrition.
What is trypsinogen
It is an inactive enzyme
Activated by: Enterokinase
Active Enzyme: Trypsin
Action: Endopeptidases (hydrolyze interior peptide bones of proteins and polypeptides)
End-products: Mixture of peptides and amino acids
What is Chymotrypsinogen
An inactive enzyme
Activated by: Trypsin
Active enzyme: Chymotrypsin
Action: Endopeptidases (hydrolyze interior peptide bonds of proteins and polypeptides)
End-products: Mixture of peptides and amino acids
What is Pro-elastase
An inactive enzyme
Activated by: Trypsin
Active enzyme: Elastase
Action: Endopeptidases (hydrolyze interior peptide bondes of proteins and polypeptides)
End-products: Mixture of peptides and amino acids
Whati s Pro-carboxy peptidases A and B
An inactive enzyme
Activated by Trypsin
Active enzyme: Carboxypeptidase A and B
Action: Exopeptidases (hydrolyze bonds at C-terminal end)
End-products: Mixture of peptides and amino acids
What is amylase
An active enzyme
Action: Cleaves starches to sugars (same as salivary amylase)
End-Products: Maltose, maltotriose, and alpha-limit dextrins
What is lipase
An active enzyme
Action: Hydrolyze triglycerides
End-products: Free fatty acids and 2-monoglycerides
What is Prephospholipase A2
An inactive enzyme
Activated by: Trypsin
Action: Hydrolyzes phospholipids
End-products: Free fatty acids and lysophospholipids
What is cholesterolesterase
An active enzyme
Action: Hydrolyzes cholesterol-esters
End-products: Free fatty acids and cholesterol
How can CCK regulate pancreatic juice secretion
Fatty acids and amino acids in the small intestine triggers CCK secretion from cells in small intestine into blood. The CCK stimulates when the pancreas to increase digestive enzyme secretion and gall bladder contraction. Fats and amino acids are absorbed and stimulation of CCK release is stopped - due to the removal
What happens during gall bladder contraction
Release of bile acids for fat breakdown. Relaxation of the sphincter of Oddi.
How does secretin regulate pancreatic HCO3- secretion
Acid enters the duodenum from the stomach. Reduced pH triggers secretin secretion from cells in small intestine into blood. The secretin stimualtes pancreas (duct cells) to increase HCO3- secretion and liver (duct cells) to increase HCO3- secretion. The stomach acid is neutralized, and stimulation of secretin release is stopped.
What are the phases of pancreatic secretion
- Cephalic Phase
- Gastric Phase
- Intestinal Phase
What is the cephalic phase of pancreatic secretion
Minor phase but sight, smell, taste and any other sense will stimulate pancreatic secretion via the parasympathetic nerves
What is the gastric phase of pancreatic secretion
Minor phase but distension of stomach will stimulate pancreatic secretion via the parasympathetic nerves
What is the intestinal phase of pancreatic secretion
Major phase of regulation. Acid from stomach in duodenum in secretin release. Digested fat and protein duodenum results in CCK release.
What is the liver
The largest internal organ of the body, receives 25% of the cardiac out, contains 4 different lobes, and extends across the entire abdominal cavity
What is the structure of a hepatic lobule in a liver
Hexagonal structure with a central vein running through the center, and portal triads at each corner
What is the structure of a portal triad of a liver
Portal triad composed of branches of hepatic artery, portal vein, and bile duct
What are the cell types that are present in the liver
Epithelial cells
Kupffer cells
Endothelial cells
What are the epithelial cells in the liver
Hepatocytes and Bile duct epithelium or cholangiocytes
What do hepatocytes do in the liver
Account for ~70% of the cells in the liver and is important for synthesizing many different components of bile
What do bile duct epithelium cells do in the liver
Account for 3-5% of the cells in the liver and they modify the components of the bile
What are Kupffer cells in the liver
They act as macrophages
What do endothelial cells do in the liver
They are lining the sinusoids and they are “fenestrated” and are thus very leaky
What are the major functions of the liver
Exocrine Gland - Formation and secretion of bile
Metabolism and storage of nutrients - Liver matches supply to demand
Deactivation and detoxification - Drugs, hormones, waste products, toxicants
Production of circulating proteins - Blood coagulation factors, lipoproteins
What are the constituents of bile
- Bile acids
- Cholesterol
- Salts and water
- Phospholipids
- Bile pigments
- Trace metals.
What is the role of bile in fat digestion
Pancreatic lipase is a water-soluble enzyme and can only work at the surface of lipid droplets. Large lipid droplets need to be made smaller for efficient access by lipase. This process is called emulsification.
What does emulsification require
Mechanical disruption to make droplets smaller through GI motility, and emulsifying agent to prevent droplets from re-aggregating into amphipathic bile acids and phospholipids
What are the micelles that can be formed in fat digestion
Bile acids can also form “mixed micelles” with phospholipids and products of lipase digestion (free fatty acids and monoglycerides). “Micelle” is a soluble cluster of amphipathic molecules with nonpolar groups in the middle and polar groups on the outer layer
What is the micelle function
Fatty acids and monoglycerides are insoluble in water. Micelles keep monoglycerides and fatty acids in small soluble aggregates. The equilibrium between the micelle and free fatty acid monoglycerides. Micelles are like a “holding station” for small non-soluble lipids.
Where is bile formed
Hepatocytes, Bile duct cells and Gall bladder
What role does hepatocytes form in bile formation
Produce and secrete bile acids, also secrete phospholipids, bile pigments, and all the components are secreted through primary active transport
How is bile formed in the bile duct cells
They add HCO3- (and other salts) and H2O to bile
How is bile formed in gall bladder
Stores and concentrates the bile between meals then expels it into the duodenum after a meal.
What is the enterohepatic circulation of bile acids
There is 20-40g of bile acids are released into the intestine each day, ~0.5g is lost in the feces. This recycling of bile acids occurs through the enterohepatic circulation. This allows for the secretion rate to greatly exceed the synthesis rate.
What are the steps of the bile acid recycling
- Bile acids are released by the liver/gall bladder into the duodenum for fat digestion
- Bile acids are reabsorbed across the small intestine (ileum) into the portal circulation
- Bile acids are transported back into hepatocytes
What factors can impact the enterohepatic circulation
Dietary fiber can squester the bile acids preventing the cycling back to the liver resulting in them being lost in feces. Certain drugs and toxins can also undergo enterohepatic circulation.
How does secretin impact the hepatobiliary secretion during intestinal phase
Secretin is produced and released by S-cells in the duodenum which are stimulated by acid in the duodenum. Secretin increases HCO3- secretion by the bile duct cells (and the pancreas)
How does cholecystokinin (CCK) impact the hepatobiliary secretion during intestinal phase
Produced by the I-cells in the duodenum and jejunum which is stimulated by digested fats/proteins in the upper small intestine. CCK increases the contraction of the gall bladder and relaxes the sphincter of Oddi and bile is released into the duodenum.
What are gallstones
Majority are “cholesterol stones”. Cholesterol is water insoluble and only kept in solution in bile through the formation of micelles with bile acids and phospholipids. If the concentration of cholesterol in bile becomes high relative to bile acids, cholesterol starts to precipitate out, “nucleating” agent also required.
What are pigment stones
Less common and caused by excessive hemolysis (red blood cell breakdown) which increases the concentration in bile, and pigments form precipitages with Ca2+
What are the consequences of gallstones
Depends on location of stones; may cause obstruction/infection of gallbladder, liver, or pancreas. Pain, nausea, jaundice, malabsorption of fats and fat-soluble vitamins.
What is the treatment of gallstones
Cholecystectomy (removal of gallbladder)
Removal of stones
Drugs to dissolve gallstones
What is the small intestine
Located between the stomach and the large intestine. Tube of 2.4cm in diameter, 3m in length. It is divided into three sections the duodenum, jejunum, and ileum.
What are the major functions of the small intestine
Digestion and absorption of protein, fat, carbohydrate, electrolytes, water, minerals, and vitamins.
What is the duodenum responsible for
Mixing of pancreatic digestive enzymes and bile with food. Absorption of nutrients, iron, and calcium. Release of endocrine hormones secretin and CCK.
What is the jejunum responsible for
Digestion and absorption
What is the ileum responsible for
Digestion and absorption primarily of bile acids and vitamin B12
What happens to chyme in the small intestine
Most of the chyme entering the small intestine is digested and absorbed in the first 25% of the small intestine (duodenum and jejunum)
How is the surface area of the small intestine increased
There is folds that increase surface area of the intestine. Villi, Crypts, Microvilli, and Enterocytes will further increase the surface area.
What makes up the structure of a villus in the small intestine
These stem cells differentiate into Paneth cells, Endocrine cells, Enterocytes, and Goblet cells. Once they reach the top of the villus they will be sloughed off and released into feces.
What do enterocytes do
They are an absorptive cell which are responsible for absorbing nutrients. They will have things coming from the intestinal lumen into cell for absorption to take place. They contain brush border enzymes.
What are goblet cells in the small intestine
Scattered through the small intestines epithelial layer. It is full of bubbles of exocytic vesicles filled with mucin.
What are the enteroendocrine cells in the small intestine
Scattered through the small intestine epithelial layer. Responsible for releasing hormones such as secretin and CCK. Across the basolateral layer across the interstitial space and into circulation
What do Paneth cells do in the small intestine
They have exocytic vesicles that are filled with antibacterial proteins. These antibacterial proteins that are released into the gastrointestinal lumen to reduce bacterial growth in the small intestine.
What is a brush border enzyme
Enzyme is anchored to the brush border with catalytic activities in the lumen. This is important for breaking down carbohydrates and peptides into sugars and amino acids prior to transport across the enterocyte.
What does brush border mean
Small projections (Microvilli) of epithelial cells covering the villi of the small intestine, major absorptive surface of the small intestine.
How are carbohydrates digested
Starch is broken down into maltose, maltotriose, and alpha-limit dextrins by salivary and pancreatic amylases. These are broken down to monosaccharide glucose by brush border enzymes. Other sugars in diet table sugar (sucrose) and milk sugar (lactose) are also broken down by brush border enzymes.
How is Glucose and Galactose absorbed internally
These sugars work their way from the intestinal lumen with the help of transporters into the epithelial cells. From the epithelial cells it using enterocytes to transport it into the blood.
How is Fructose internally absorbed
This is facilitated compared to other sugars and it easily makes it way from the intestinal lumen, epithelial cells, and blood.
What is lactose
The milk sugar lactose is digested by brush border enzyme lactase in the small intestine into the monosaccharide’s glucose and galactose.
What causes lactose intolerance.
All mammals including humans lose lactase expression (to varying degrees) post-weaning from milk. So they can’t completely digest lactose.
What happens when someone is lactose intolerant
Results in decreased water absorption in the gut (presence of lactose produces an osmotic gradient). Lactose-containing fluid passes on to large intestines and bacteria digest lactose. This will cause gas (colon distension, pain) and diarrhea.
How can you treat lactose intolerance
Can come lactase pills with meal or ingest “lactose free” dairy products that has been pre-treated with lactase.
How is protein digested into the small intestine
Proteins are broken down by pepsin in the stomach, and in the small intestine by pancreatic proteases. Once digested, free amino acids are absorbed by secondary active transport coupled to Na+. Small peptides can also be absorbed by different secondary active transport proteins coupled to H+. Amino acids then undergo facilitated diffusion across the basolateral surface of the enterocyte.
What are carboxypeptidases
Enzyme that is pancreatic protease
What is aminopeptidases
A brush border enzyme that is in the small intestine
How is fat digested into the small intestine
Products of lipase are incorporated into micelles which are in dynamic state-breaking down and reforming. As micelles breakdown, they will release fatty acids and monoglycerides that can then go across the small intestine epithelium. Once absorbed by the enterocyte fatty acids and monoglycerides are processed by the endoplasmic reticulum back into triglycerides
What happens to fat once it makes into into the endoplasmic reticulum
Within the endoplasmic reticulum triglycerides aggregate into lipid droplets coated with amphipathic proteins. Lipid droplets packaged in the Golgi and secreted via exocytosis. Extracellular fat droplets know as “chylomicrons”
What is chylomicron
Chylomicron contains triglycerides, phospholipids, fat soluble vitamins, and cholesterol. The large chylomicron enters the lymphatic system.
How is iron absorbed into the small intestine
Iron is the oxygen binding component in red blood cells and a key component of many enzymes. Iron (as Fe2+) is actively transported into the enterocyte and incorporated into the protein ferritin.
What happens to iron that is not stored from the small intestine
Iron that is not stored is released on the blood side of the enterocyte and transported through the blood attached to the plasma protein transferrin.
What happens to iron when it is bound to ferritin
Iron that remains in the enterocyte bound to ferritin is excreted from the body when the enterocytes slough off the villi tips.
What happens when iron supplies are ample
When iron stores are ample in the body expression of ferritin protein is upregulated resulting in a reduced absorption of iron.
What happens when irons stores are depelted
When iron stores are depleted the production of intestinal ferritin decrease resulting in increased absorption
What happens when you have iron toxicity
When the body has excess iron this can result in toxicity, including skin pigmentation, and heart failure. This can be caused by genetic defects in absorption control pathways, adult males/post-menopausal women excessively supplementing, poisoned children.
What is the treatment of iron toxicity
Bloodletting and sometimes self-imposed vomiting and diarrhea through use of laxatives
What is iron-reduced anemia
Redcued number and/or size of red blood cells. The symptoms are tiredness, light-headedness, and headaches. It is caused by not enough iron in the diet, loss of iron through blood loss, poor iron absorption and intestinal diseases.
What is the treatments for iron-deficiency anemia
Iron supplements, iron infusions, iron salts, vitamin B12, heme iron, and iron in its Fe2+ form
Why are water and electrolytes important for the small intestine
Control of fluid in intestine is critical for GI function which permits contact between food and digestive enzymes. Diffusion of digested nutrients to absorption. Fluidity provides for transmit without damage to the epithelium.
How does the small intestine handles fluid
Intestine handles large quantities of fluids each day, some of it front the diet. Majority from the intestine and organs is drained and reabsorbed by the small intestine
How much fluid is handled by the GI tract each day?
8-9 liters each day. Only 100 mL is lost in feces. The majority of the fluid is absorbed into the blood from the small intestines
How is water absorbed into the small intestine
Predominantly depends on Na+ gradients generated during secondary active nutrient uptake of glucose and galactose
How is water secreted from the small intestine
Predominantly depends on Cl- gradients generated by the secondary active Na+/K+/2Cl- transporter. Generally, this happens in the crypt cells
What is Cholera
Occurs after eating food or drinking water contaminated with Vibrio cholerae bacteria. It causes vomiting and excessive diarrhea - upwards of 20 litres of stool per day versus the normal 0.1 litre). This can lead to dehydration, electrolyte imbalance and death if left untreated
How does the bacteria Vibrio cholerae impact the intestines
Vibrio cholerae produce a toxin that drastically increases the production of cAMP in the cyrpt epithelium of the small intestine. This results in the activation of the Cl- channel and excessive secretion of Cl- in the gut lumen, water follows leading to diarrhea.
How is cholerae treated
Consumption of clean water containing salt and glucose through fluid replacement. Intravenous fluids.
How does the small intestine move during digestion
Most common motion in small intestine during digestion is “segmentation? There is continuous division and subdivision of intestinal contents. The frequency of contraction set by basic electrical rhythm. Contraction force is determined by neurohormonal input. There is a slow net migration towards the large intestine
How is the continuous division and subdivision of intestinal contents during digestion
Mechanical breakdown of food which increases surface area and mixing of food with digestive enzymes.
What is the frequency of contractions in the small intestine during digestion
12 contractions per minute in the duodenum
9 contractions per minute in the ileum
What is the motility of the small intestine after absorption
The contractions of the small intestine stops and is replaced by a pattern of peristaltic activity called the migrating myoelectric complex. This begins in lower portion of the stomach travels about 2 feet along the small intestine and then dies out. Next overlapping wave starts further down the small intestine, and this is repeated along the small intestine which takes roughly 2 hours and then repeats.
What is the purpose of the migrating myoelectric complex
It pushes any undigested material from the small to the large intestne and prevents from remaining in the small intestine
How is the migrating myoelectric complex regulated
The intestinal hormone motilitn which is released by cells in the small intestine through tone initiated the migrating myoelectric complex. When you eat it inhibits the release of motilin and the MMC will cease when next meal is consumed.
What is the large intestine
Tube of approximately 6.5 centimetres in diameter and 1.5 metes in length. It was made up of the cecum/appendix, ascending/transverse/descending/sigmoidal colon, rectum, and anus
What is the ileocecal valve
The valve between the large and small intestine, the sphincter between the cecum and ileum. It opens when the ileum contracts (post-meal), and closes when intestine is distended. It retains large intestine contents including bacteria
What is the cecum/appendix in the large intestine
No apparent function in humans. In some other species it is well developed and contains commensal bacteria important for digesting complex carbohydrates.
What is the major functions of the colon
Reabsorption, reservoir for the storage of wastes and indigestible materials prior to elimination by defecation, and absorption of products of bacterial metabolism
What does the rectum do
Reservoir for feces
What does the anus do
It has two sphincters (inner and outer) to control defecation
What are the large intestine cell types
Large intestine only contains crypts (no villi) so the surface area is much lower than the small intestine. The cells that make up the large intestine are absorptive cells/enterocytes, goblet cells, paneth cells, and endocrine cells.
What are the stem cells in the large intestine
Stem cells are found in the crypts and they will differentiate into one of the four different epithelial cell types.
What is the ecosystem of bacteria in the large intestine
It is the “gut microbiome” and the healthy adult gut contains over 1000 species of bacteria. They can liberate short chain fatty acids from dietary fibre that are absorbed. They can also absorb vitamines that are. The ecosystem can be influenced by diet, medications, and bowel function. It had a large implication on health.
What can cause problems in the ecosystem of the large intestine
Obesity, allergies, clostridium difficile infection, inflammatory bowel disease, toxicant metabolism and malabsorption
What is Clostridium difficile infection
It is an antibiotic-resistant infection that can lead to issues with integrity in the gastrointestinal tract wall and it is treated with a poop transplant
How is water absorbed in the large intestine
Predominantly depends on Na+ gradients generated by Na+/K+ ATPase
What is the secretion of water in the large intestine
Predominantly depends on Cl- gradients generated by secondary Na+/K+/2Cl-
What is motility in the large intestine
Mixing the contents and retaining them for optimal salvage of fluid and bacterial products.
What is mixing in the large intestine
Segmentation that is much slower with the basic electrical rhythm and allows for retention in the colon for 18-24 hours.
What is propulsion of the large intestine
Occurs three to four times a day there is a wave of intense contraction known as a “mass movement” spreads rapidly over the large intestine, pushing content towards the anus. Occurs after eating and prior to defecation
What is feces
Feces made up of water, undigested food, bacteria, and sloughed epithelial cells.
What is defecation
Initiating by the mass movement of large intestine contents into the rectum. They rectum distends and mechanoreceptor activated.
What is the reflex of defecation
Rectum contracts, internal anal sphincter relaxes and the outer anal sphincter contracts. There is an increased peristaltic activity in the sigmoid colon, increasing pressures results in reflex relaxation of the external anal sphincter. The feces is then voided.
How can the brain override the reflex of defecation
After toilet training, brain can override the reflex relaxation of the outer sphincter resulting in delayed defecation. This causes reverse peristalsis then occurs, and rectal contents move back into the sigmoidal colon.
What happens during water secretion in the large intestine
Water secretion depends on the Cl- gradient generated by the secondary active transport by NKCC1 (Na+/K+/2Cl- transporter)
What is aminopeptidase
Brush border enzyme
Where are chylomicrons found during fat digestion and absorption
Chylomicrons are released across the basolateral surface of the enterocyte, and enters the lymphatic system by diffusing into lacteals.
What is true about acetylcholine and acid secretion
Acetylcholine can increase acid secretion by inhibiting somatostatin release
What hormones make a person feel hungry and therefore increase food intake
Neuropeptide Y
What does gastrointestinal motility do during segmentation
Segmentation slows the transit time of the small intestine contents to allow for the absorption of nutrients
How is secretin stimulated
Secretin release is stimulated mainly by acid in duodenum
How is the extrinsic neuronal regulation of the gastrointestinal tract influenced
Influences the gastrointestinal tract through the autonomic nervous system
Which enzyme is responsible for activating trypsinogen to trypsin and where does it occur
Enterokinase is responsible for activating trypsinogen to trypsin in the duodenum
