Flashcards in Gastrointestinal System Deck (153):
What is digestion?
Breaking down macromolecules (nutrients) into forms that can be transported across the epithelium.
What is absorption?
The transport of nutrients, water, ions, and vitamins across the epithelium.
What do you need in order to accomplish digestion and absorption?
- Secretion (release of enzymes into gut lumen)
- Motility (keep the gut contents moving)
What are some additional considerations in order to maintain proper GI function?
- The ability to digest macromolecules but not itself.
- The ability to allow entry of digested nutrients but not pathogens.
- The ability to maintain balance between water input/output.
Protection from pathogens is mediated by:
- Epithelial barrier
- Digestive enzymes
- Gut-Associated Lymphoid Tissue (GALT)
What is the purpose of GALT?
To react to pathogens but not to "foreign" proteins associated with food.
What are some sources of fluid input (into the GI tract)?
- Gastric secretions
- Pancreatic secretions
- Intestinal secretions
What are the 4 parts/sections of the stomach?
What are the 3 parts/sections of the small intestine?
What are the layers of the mucosal surface (from top to bottom)?
- Smooth muscle layers
What are the 3 layers of the mucosa (from top to bottom)?
- Lamina propria
- Muscularis mucosa
Which layer is a part of the submucosa?
Meissner's (submucosal) plexus
What are the 3 layers part of the smooth muscle layers?
- Circular muscle
- Auerbach's (myenteric) plexus
- Longitudinal muscle
How does the small intestine's microanatomy differ from the stomach's?
The small intestine does not have epithelium. Instead, it has villi and crypts.
It also has Peyer's patch (absent in stomach), and does not have lamina propria (present in stomach).
What are the 2 major patterns of contraction?
1) Peristalsis (moving food from mouth to anus)
2) Segmental contractions: Mixing/Churning (maximizing exposure to digestive enzymes and epithelium)
What is most gut muscle connected by?
Which regions of the gut contract tonically (minutes to hours)?
- Smooth muscle sphincters
- Anterior part of stomach
Which regions of the gut contract phasically (few seconds)?
- Posterior stomach
- Small intestine
What happens in the GI tract between meals? What happens during/after meals?
Between: Migrating motor complexes sweep slowly down tract
During/after: Peristaltic and segmental contractions
Where are single-unit smooth muscle cells most commonly found?
- Walls of GI and urinary tract
- Blood vessels
When do action potentials fire?
When slow wave potentials exceed threshold.
What are the force and duration of muscle contraction directly related to?
The amplitude and frequency of action potentials.
In the gut smooth muscle, what does it mean when the degree of contraction is graded according to the amount of Ca that enters?
Longer wave -> More time for Ca to enter -> Larger contraction
In the gut smooth muscle, what is the amplitude and duration of contraction influenced by?
- Neurotransmitters (autonomic input)
- Paracrine factors
How does the slow wave frequency vary in different regions of the GI tract?
More frequent in duodenum vs. stomach.
What are the interstitial cells of Cajal?
Pacemaker cells between smooth muscle layers that set the slow wave potential (which leads to contraction).
How are water and ions secreted into the gut?
- Via membrane transporters
- Following an osmotic gradient
- Passing between cells (paracellular)
True or False: The gut contains different channels/transporters than the kidney in order to secrete water and ions.
False. Still contain ENaC, Na/K-ATPase, NKCC, etc.
How does the pH of the lumen differ from the pH of parietal cells?
Lumen: pH = 1
Parietal cell: pH = 7.2
As H+ is secreted from the apical side, what happens to bicarb?
It is absorbed into the blood (basolateral side).
What is the purpose of secreting bicarb into the duodenum?
To neutralize acid arriving from the stomach.
What are acinar cells?
From the pancreas, and secrete enzymes.
What do the epithelial cells lining the pancreatic duct secrete?
What is the process of bicarb secretion?
1) CO2 enters the pancreatic duct cell or duodenal cell, and combines with H2O to produce bicarb and H+.
2) H+ is secreted out the basolateral side in exchange for Na+.
3) Cl- enters the cell via basolateral NKCC transporter and leaves via apical CFTR channel.
4) Bicarb is secreted out via apical Cl-/bicarb exchanger.
5) Cl- in lumen attracts water and Na+.
What does bicarb secretion require (high expression of ______)?
What is the process of NaCl secretion in the small intestine, colon, and salivary glands?
1) Na, K, and Cl enter via NKCC transporter.
2) Cl enters lumen through CFTR channel.
3) Na is reabsorbed
4) Negative Cl in lumen attracts positive Na by paracellular pathway.
5) Water follows.
What do crypt cells secrete?
Isotonic saline that mixes with mucus secreted by goblet cells to lubricate gut contents.
What is Cystic Fibrosis?
A mutation in gene that encodes in CFTR channel.
Leads to defects in Cl- and water transport.
What is the process of Cystic Fibrosis causing pancreatic damage?
1) Cl not transported into ducts.
2) Various effects, including decreased Na and water transport into ducts.
3) Mucus still produced but greatly thickened due to lack of water.
4) Blockage of pancreatic ducts.
5) Exocrine secretions of pancreas not released (bicarb, enzymes).
6) Back pressure/inflammation
7) Damage to pancreas.
Where are enzymes secreted by either exocrine glands or epithelial cells of stomach/small intestine synthesized? Where are the packaged? Where are they stored?
Synthesized by rough ER.
Packaged by Golgi.
Stored in cell.
Why are enzymes sometimes released as zymogens?
To prevent auto-digestion.
What is enzyme secretion regulated by?
Neural, hormonal, and paracrine signals.
What is enzyme secretion usually stimulated by?
Parasympathetic stimulation (via vagus).
What does mucus primarily consist of?
"Mucins", a mixture of glycoproteins.
What is mucus produced by?
- Serous cells in salivary glands.
- Mucous cells in stomach.
- Goblet cells in intestine.
What are some signals for mucus secretion?
- Parasympathetic stimulation.
- Various neuropeptides (of enteric nervous system).
- Cytokines (from immune cells in response to infection/inflammation).
What is saliva?
Complex hypo-osmotic fluid.
Made up of water, ions, mucus, proteins (enzymes, immunoglobulins).
What is the 2 step process of saliva secretion?
1) Fluid secreted by acinar cells similar to ECF (isotonic saline).
2) As it passes through ducts, epithelial cells take back Na and secrete K, eventually resembling ICF. Water remains in saliva (hypo osmotic).
How is saliva secretion stimulated?
Stimulated: Parasympathetic pathways
Inhibited: Sympathetic pathways
Where is the sphincter of Oddi located?
What is the organization of bile secretion through the hepatic lobule?
2) Bile Canaliculi
3) Bile ductules
4) Common hepatic duct & Gall bladder
5) Common bile duct
Where do most absorbed nutrients move into?
Capillaries in villi, then into the hepatic portal vein.
What must xenobiotics first pass through before reaching systemic circulation?
True or False: Fats also go into the blood vessels.
False. Fats go into the lymphatic system instead of blood.
The hepatic artery and the hepatic vein connect in which structure?
Sinusoids in the liver.
What are the key components of bile?
- Bile salts
- Bile pigments
What are some purposes of the liver?
- Glucose and fat metabolism.
- Protein synthesis.
- Hormone synthesis.
- Urea production.
What does the liver secrete into the duodenum?
- Bile salts
- Water, ions
What metabolites does the liver secrete into peripheral tissue?
- Plasma proteins
- Vitamin D, somatomedins
What is the organization of blood flow through the hepatic lobule?
1) Hepatic artery & Hepatic portal vein
3) Central vein
4) Hepatic vein
What does it mean when the sinusoids are "very aappy"?
A lot of plasma filtered out -> lymph.
A lot of proteins added in.
What is bilirubin responsible for?
- Normal color of feces.
- Normal color of urine.
How is bilirubin also an indication of injury/pathology?
- Responsible for the yellow phase of bruises.
- Responsible for the yellow pigmentation of jaundice (hyper bilirubin emia).
What is the process of hemoglobin, iron, and RBC turnover?
1) Iron ingested from diet.
2) Fe absorbed by active transport.
3) Transferrin protein transports Fe in plasma.
4) Bone marrow uses Fe to make Hb as part of RBC synthesis.
5) RBC's live about 120 days in the blood.
6) Spleen destroys old RBC's and converts Hb to bilirubin.
7) Bilirubin and metabolites are excreted in urine and feces.
8) Liver metabolizes bilirubin and excretes it in bile.
9) Liver stores excess Fe as ferritin.
Where does digestion occur?
In mouth, stomach, and small intestine.
Where does absorption occur?
Mostly in the small intestine, with some ions and water absorbed in large intestine.
True or False: Digestion and absorption are regulated.
False. Not directly regulated.
Which nutritional group constitutes half of caloric intake?
How can monosaccharides be absorbed?
Only via a membrane transporter.
How do artificial sweeteners work?
They interact with "sweet" receptors, but cannot be digested to a form than can cross into enterocytes (cells of the intestinal lining).
How are carbohydrates digested and absorbed?
1) Amylase is used to digest glucose polymers into disaccharides.
2) Maltase, sucrase, and lactase digest maltose, sucrose, and lactose into monosaccharides.
3) Glucose & galactose enter with Na, using SGLT, and exits using GLUT2.
4) Fructose enters using GLUT5, and also exits using GLUT2.
What is the process of protein digestion?
1) Endopeptidase (proteases) digests internal peptide bonds.
2) Exopeptidases digest terminal peptide bonds to release AA's.
What is the process of protein absorption?
1) Proteins are digested into peptides.
2) Di and tripeptides cotransport with H+.
3) AA's cotransport with Na+.
4) Small peptides are carried intact across the cell by transcytosis.
5) In the cell, di and tripeptdies and cleaved by peptidases to also become AA's.
6) All AA's are then transported out of the cell and into the blood stream to the liver. Uses Na antiport.
Which step of protein absorption only occurs in the first few hours-days of life, prior to "gut closure"?
Carrying small peptides intact, across the cell by transcytosis.
What are some examples of fats?
Triglycerides, cholesterol, phospholipids, long chain fatty acids, fat soluble vitamins.
In what form does fat leave the stomach?
As large droplets mixed with aqueous chyme.
Low surface area available to interact with enzymes.
How are fats broken down?
Through the action of bile salts (derivatives of cholesterol).
How are bile salts (bile acids) made?
1) Cholesterol is broken down into primary bile acids (cholic acid and chenodeoxycholic acid).
2) Primary bile acids are then modified by gut bacteria to become secondary bile acids.
3) Primary bile acids can also bypass modification and go straight to conjugation in the liver to become the final conjugated bile acid.
4) Secondary bile acids will also be conjugated in the liver.
What do bile salts do (wrt fat digestion)?
Coat lipids to make emulsions of large droplets.
The hydrophobic side associates with the lipid, and the polar side chain (hydrophilic) associates with water.
Which enzyme helps pancreatic lipases act on triglycerides?
Colipase, from pancreas.
True or False: All fats are digested into smaller components, EXCEPT cholesterol.
What is the process of fat absorption?
1) Bile salts coat fat droplets.
2) Pancreatic lipases and colipase break down fats into monoglycerides and fatty acids.
3) Monoglycerides and fatty acids diffuse from micelles and cross cell membranes.
4) Cholesterol is transported into cells.
5) Absorbed fats combine with cholesterol and proteins in intestinal cells to form chylomicrons.
6) Chylomicrons removed by lymphatic systems.
What happens to monoglycerides and free fatty acids in the smooth ER?
They recombine into triglycerides.
Do all fats enter the lymphatic system?
No, short fatty acids can travel solo, entering capillaries rather than lymph.
What is the process of nucleic acid digestion and absorption?
1) Gastric and pancreatic proteases break down nucleoproteins into nucleic acids.
2) Nucleases break down nucleic acids into nucleotides.
3) PO4- leaves, turning nucleotides into nucleosides.
4) Nucleosides are then absorbed by Na-coupled transport, and broken down to purines/pyrimidines and ribose/deoxyribose in tissues.
5) Various metabolic pathways.
How are vitamins absorbed?
Fat soluble: In small intestine along with fats.
Water soluble: In small intestine via membrane transporters.
Which vitamins are fat soluble?
Which vitamins are water soluble?
Fat soluble: A, D, E, K
Water soluble: C, most B's
What is the only exception in vitamin absorption?
What is it particularly important for?
B12. Absorbed in the ileum and requires protein secreted by gastric parietal cells (intrinsic factor).
Particularly important for RBC synthesis.
What happens if there is a deficiency of intrinsic factor?
Leads to deficiency of B12 that cannot be corrected by oral B12 supplementation.
What is the process of absorption of ions and water by small and large intestine?
1) Na enters cells by multiple pathways.
2) Na/K-ATPase pumps Na into ECF.
3) Water and K+ move through the cell into ECF by paracellular pathway.
True or False: The absorption of iron and calcium is regulated.
However, for calcium, only transcellular transport is regulated. Paracellular is not.
How is iron absorption regulated?
1) Iron is brought through the apical side with H+, using DMT1.
2) Iron then diffuses out into the interstitium using Ferroportin.
How is calcium absorption regulated?
1) Ca is brought through the apical side using Ca channels.
2) Ca uses Na antiport or ATPase to travel through to the interstitium.
Where are "long" reflexes of GI function integrated?
What about "short" reflexes?
Long: In the CNS.
Short: Within gut (enteric nervous system).
What type of reflex are cephalic reflexes a part of?
"Long" reflexes, and more specifically, feedforward reflexes.
What are cephalic reflexes?
In response to sight, smell, thought of food, effects of emotion.
Which branch of the autonomic nervous system is responsible for excitatory pathways?
Which branch is responsible for inhibitory pathways?
Where do neurons in the submucosal plexus receive signals from?
What do they regulate?
They regulate secretion.
What do neurons in the myenteric plexus regulate?
Are reflexes involving gut peptides paracrine or endocrine?
Both. Some can even act on the brain and be produced there.
What do reflexes involving gut peptides have an effect on?
Motility (altered peristalsis, gastric emptying), and both endocrine and exocrine secretion.
What are some parallels between the enteric and central nervous systems?
1) ENS has intrinsic neurons that lie entirely within gut (similar to interneurons of CNS).
2) ENS releases more than 30 different neurotransmitters and neuromodulators. Similar to molecules used in CNS.
3) Has glial support cells, similar to astrocytes of CNS.
4) Diffusion barrier-capillaries surrounding ganglia are not very permeable, similar to blood-brain barrier.
5) Acts as an integrating center.
If the enteric nervous system can act as its own integrating center, what does that mean?
Gut function can be regulated without the CNS.
What did Pavlov research wrt endocrinology?
Acid chyme passing into the duodenum would cause pancreatic juice to secrete into the duodenum.
Thought that pancreas secretion was controlled only by the vagus nerve. Vagal afferents from duodenum -> brain -> vagal efferents to pancreas.
How did Bayliss and Starling contribute to our understanding of endocrinology?
They carefully dissected away all nerves surrounding the pancreas and duodenum, but when they put acid in the duodenum, the pancreas still secreted.
Therefore, the acid itself caused release of signal from duodenum into blood.
They collected the lining of the duodenum, added acid to it, and injected it intravenously. There was indeed pancreatic secretion.
Which factor from the intestine stimulates pancreatic secretion?
What are the major targets of the gastrin family?
Stomach, intestine, and accessory organs.
What are the targets of the secretin family?
Endo and exocrine targets.
What is the target of motilin, and what does it do?
It acts on gut smooth muscle, and regulates migrating motor complexes.
What is the purpose of saliva? What is it made of?
Soften and lubricate food.
It is made of salivary amylase and some lipase.
What is mastication?
What is deglutition?
Transferring food from the mouth to the stomach.
What is the swallowing reflex?
1) Tongue pushes bolus against soft palate and back of mouth, triggering swallowing reflex.
2) Breathing inhibited as bolus passes closed airway.
3) Food moves downward into esophagus, propelled by peristaltic waves and aided by gravity.
What is the purpose of the epiglottis during swallowing?
It folds down to help keep swallowed material out of the airway.
Where is the swallowing reflex integrated?
In the medulla.
Which structure is responsible for guarding the entry into the stomach?
The lower esophageal sphincter, a tonically contracted ring of smooth muscle.
What happens if the lower esophageal sphincter is not closed?
Acid from the stomach can splash up into the lower esophagus.
This can happen during respiration (when intrathoracic pressure drops), or during the churning of stomach (heartburn).
What is another name for heartburn?
Gastroesophageal reflux disease (GERD).
What happens during the anticipation of food/presence of food in mouth?
1) Anticipation/presence of food.
2) Activation of neurons in medulla.
3) Efferent signals to salivary glands.
4) Autonomic signals via vagus to ENS.
5) Increase motility and secretion in stomach, intestine, and accessory organs.
What is the cephalic phase initiated with?
Initiated with long vagal reflex.
What is the gastric phase?
Once food enters stomach, series of short reflexes.
What are the 3 functions of the stomach?
1) Storage: Neurally mediated "receptive relaxation" of upper stomach.
2) Digestion: Mechanical and chemical processing into chyme.
3) Protection: Against microbes (acid) and itself (mucus-bicarb barrier).
What is the purpose of chief cells?
What are 2 examples of chief cells?
Pepsin: Digest proteins.
Gastric lipase: Digest fats.
What is the purpose of somatostatin from D cells?
Inhibit gastric acid secretion.
What is the purpose of enterochromaffin-like cells?
What is an example of this type of cell?
Stimulates gastric acid secretion.
What are the functions of parietal cells?
- Activates pepsin
- Denatures proteins
How is gastrin from G cells triggered, and what is their function?
Triggered by both long and short loop reflexes.
They have multiple roles.
What is the process of integration between the cephalic and gastric phases?
1) Food or cephalic reflexes initiate gastric secretion.
2) Gastrin stimulates acid secretion by direct action on parietal cells or indirectly through histamine.
3) Acid stimulates short reflex secretion of pepsinogen.
4) Somatostatin release by H+ is feedback signal that modulates acid and pepsin release.
What is a peptic ulcer?
Breakdown of mucus-bicarb barrier.
Acid and pepsin damage mucosal surface, creating holes that extend into submucosa and muscularis layers.
What are some treatments for ulcers?
- Antacids, which neutralize gastric acid.
- H2 receptor antagonists, which block histamine action.
- Proton pump inhibitors, which block H+/K+-ATPase.
What is the process of stimulation of parietal cell acid secretion?
Gastrin, histamine, and ACh cause the internal H+/K+-ATPases to become external.
What is the intestinal phase?
Begins with controlled entry of chyme into the small intestine.
Sensors in duodenum feed back to stomach to control delivery of chyme, feed forward to intestine to promote digestion, motility, and nutrient utilization.
During the intestinal phase, what is the purpose of bicarb and which cells is it secreted from?
Secreted from the pancreas (duct cells), and neutralizes chyme.
During the intestinal phase, what is the purpose of mucus and which cells is it secreted from?
Secreted from goblet cells, and is for protection and lubrication.
During the intestinal phase, what is the purpose of bile and where is it secreted from?
Secreted from the gall bladder (liver) and the major function is fat digestion.
During the intestinal phase, what is the purpose of enzymes (as zymogens) and where is it secreted from?
Secreted from the pancreas brush border, and is a major factor in digestion.
What do CCK's stimulate the release of?
Bile and enzymes (as zymogens).
What is the enterohepatic circulation of bile salts?
Bile salts are released into duodenum, absorbed in terminal ileum, enter portal circulation, and travel back to liver.
True or False: Bile salts cannot be recycled during meals.
False. They are recycled several times during a meal.
How are pancreatic zymogens activated?
1) Pancreatic secretions are secreted into the lumen of the small intestine.
2) Enteropeptidase in brush border activates trypsin (from trypsinogen).
3) Trypsin activates zymogens and turns them into activated enzymes.
What does the defecation reflex begin with?
Distension of rectal wall.
What is the site of fluid secretion?
What is the role of the large intestine?
Removes most of the remaining water -> Formation of feces.
When does an ileocecal valve relax?
Each time a peristaltic wave reaches it, or when food leaves the stomach.
What is the gastroileal reflex?
When food leaves the stomach.
What is diarrhea?
An imbalance between intestinal absorption and secretion.
What is osmotic diarrhea?
Unabsorbed osmotically active solutes.
Due to undigested lactose, sorbitol, or Olestra (fake fat), or osmotic laxatives.
What is secretory diarrhea?
When bacterial toxins increase Cl- secretion.
Diarrhea can be adaptive (flushing out infection), but it can also lead to ________?
Dehydration and/or metabolic acidosis.
What is cholera?
An intestinal infection due to contaminated food/water.
How does cholera affect the Ga subunit?
The Ga is irreversibly modified by addition of an ADP-ribosyl group. The modified Ga can bind GTP but cannot hydrolyze it. As a result, there is an excessive, nonregulated rise in cAMP level.
What is the process of intracellular trafficking of cholera toxin (CT)?
1) Enters cell via pentameric B subunits.
2) Travels in retrograde direction through Golgi.
3) Sequence on A2 subunit recognized as signal to be shuttled to ER.
4) Mimics a misfolded protein and gets dumped out into cytosol.
5) Intead, A1 subunit modifies Ga subunit - remains bound to GTP.
6) Persistent activation of adenylyl cyclase and elevation of cAMP.
7) Sustained activation of CFTR channel.