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271 Cards in this Set
- Front
- Back
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What are the structural components of the GI tract?
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Epithelial cells
Muscularis mucosa Circular muscle Longitudinal muscle Submucosal plexus (Meissner's plexus) and myenteric plexus |
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How is the epithelium of the GI tract specialized?
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Different regions are specialized for secretion or absorption
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What does the muscularis mucosa do?
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Contraction causes a change in the surface area for secretion or absorption
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What does the circular muscle of the GI tract do?
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Causes the lumen to decrease in diameter
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What does the longitudinal muscle of the GI tract do?
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Shortens a segment of the GI tract
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What are the functions of the submucosal plexus and the myenteric plexus?
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These make up the enteric nervous system of the gut
They integrate the motility, secretory, and endocrine functions of the GI tract |
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What is another name for the submucosal plexus?
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Meissner's plexus
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What is another name for the myenteric plexus?
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Auerbach's plexus
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Is the parasympathetic nervous system generally inhibitory or excitatory in the GI tract?
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Excitatory
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What nerves convey parasympathetic fibers to the gut?
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The vagus and pelvic nerves
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Where do parasympathetic fibers synapse in the gut?
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Both the submucosal and myenteric plexuses
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What specific structures are innervated by the vagus nerve?
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Esophagus
Stomach Pancreas Upper large intestine |
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What are vagovagal reflexes?
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Reflexes where both the afferent and efferent pathways are contained in the vagus nerve
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What specific structures are innervated by the pelvic nerve?
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Lower larger intestine
Rectum Anus |
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Is the sympathetic nervous system generally inhibitory or excitatory in the GI system?
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Inhibitory
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What is the pathway of sympathetic innervation?
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Fibers originate between T8 and L2
Synapse in the prevertebral ganglia Synapse in the myenteric and submucosal plexuses, as well as directly upon blood vessels and smooth muscle Cell bodies in the plexuses send information to smooth muscle, secretory, and endocrine cells |
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What does the enteric nervous system do?
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Coordinates and relays information from the parasympathetic and sympathetic systems to the GI tract
Uses local reflexes to relay information within the GI tract Controls most GI activity, especially motility and secretion, even if there is no extrinsic innervation? |
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What is the extrinsic innervation of the gut?
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Sympathetic and parasympathetic nervous system
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What is the intrinsic innervation of the gut?
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Enteric nervous system
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What does the myenteric plexus do?
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Controls motility of GI smooth muscle
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What does the submucosal plexus do?
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Controls secretion and blood flow
Receives sensory information from chemoreceptors and mechanoreceptors |
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What are GI hormones?
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Substances that are released from endocrine cells in the GI mucosa that travel via the portal circulation to systemic circulation, and then exert a physiologic action upon target cells
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What are the GI hormones?
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Gastrin
Cholecystokinin (CCK) Secretin Glucose-dependent insulinotropic peptide (GIP) |
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What are the types of gastrin, and what is the difference?
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Little gastrin -- 17 amino acids, secreted in response to a meal
Big gastrin -- 34 amino acids, not a dimer of little gastrin |
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Where is the biologic activity of gastrin located?
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The 4 C' amino acids
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What does gastrin do?
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Stimulates HCl secretion by parietal cells
Stimulates growth of the gastric mucosa by stimulating the synthesis of RNA and new protein |
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What is observed in patients with gastrin-secreting tumors?
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Hypertrophy and hyperplasia of the gastric mucosa
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Where is gastrin produced?
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G cells in the antrum of the stomach
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What causes gastrin to be produced?
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Small peptides and amino acids in the lumen of the stomach
Stomach distention Vagal stimulation mediated by gastrin-releasing peptide (GRP) |
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What amino acids are the most important gastrin secretagogues?
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Phenylalanine
Tryptophan |
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Why doesn't atropine block vagally mediated gastrin secretion?
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The mediator of the vagal effect (the neurotransmitter, if you will) is GRP, not ACh
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What inhibits gastrin secretion?
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H in the stomach lumen
Somatostatin |
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What is Zollinger-Ellison syndrome?
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Gastrinoma
Gastrin is secreted by non-B cell tumors of the pancreas |
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How does the structure of CCK compare to that of gastrin?
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33 amino acids
Homologous to gastrin Shares the same C' 5 amino acids with gastrin |
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Where is the biologic activity of CCK located?
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The C' 5 amino acids
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Why does CCK have some of gastrin's activity in addition to its own function?
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It contains the biologically active gastrin motif
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What does CCK do?
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Stimulates contraction of the gallbladder to release bile
Relaxes the sphincter of Oddi Stimulates growth of the exocrine pancreas Inhibits gastric emptying |
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What causes CCK to be released?
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Small peptides and amino acids in the intestinal lumen
Fatty acids and monoglycerides |
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Where is CCK produced?
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I cells of the duodenal and jejunal mucosa
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Why don't triglycerides stimulate CCK release?
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They cannot cross intestinal cell membranes
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What are the important structural features of secretin?
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27 amino acids
Homologous to glucagon All amino acids are required for activity |
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What does secretin do?
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Stimulates pancreatic bicarbonate secretion
Promotes growth of the exocrine pancreas Stimulates bicarbonate and water secretion by the liver Increases bile production Inhibits acid secretion by parietal cells |
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What stimulates secretin release?
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H in the duodenal lumen
Fatty acids in the duodenal lumen |
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What hormones is GIP homologous to?
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Secretin
Glucagon |
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What does GIP do?
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Stimulates insulin release in response to oral glucose (NOT intravenous glucose)
Inhibits acid secretion by parietal cells |
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What causes GIP to be released?
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Fatty acids in the duodenal lumen
Amino acids Oral glucose loads |
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What are paracrine factors?
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Released from endocrine cells
Instead of going into systemic circulation, they diffuse over short distances to act upon target cells |
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What are the GI paracrine factors?
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Somatostatin
Histamine |
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What does somatostatin do?
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Inhibits the release of all GI hormones
Inhibits gastric acid secretion? |
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Where is somatostatin produced?
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Cells throughout the GI tract
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Where is histamine produced?
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Mast cells of the gastric mucosa
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What causes GIP to be released?
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Fatty acids in the duodenal lumen
Amino acids Oral glucose loads |
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Where is GIP produced?
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Duodenum and jejunum
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What are the GI paracrine factors?
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Somatostatin
Histamine |
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What causes somatostatin to be produced?
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Acid in the lumen
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What does histamine do?
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Increases gastric acid secretion
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What are neurocrine factors?
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Molecules that are synthesized in the neurons of the GI tract
Move by axonal transport down the axon Released by action potentials in the nerves Diffuse across the synaptic cleft to act upon target cells |
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What are the GI neurocrine factors?
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Vasoactive intestinal peptide (VIP)
GRP (bombesin) Enkephalins |
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What hormone is VIP homologous to?
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Secretin
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Where is VIP produced?
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Neurons in the mucosa and smooth muscle of the GI tract
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What does VIP do?
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Relaxes the GI smooth muscle, including the lower esophageal sphincter
Stimulates pancreatic bicarbonate secretion Inhibits gastric acid secretion |
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What factor mediates pancreatic cholera?
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VIP
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Under what conditions might VIP be abnormally secreted?
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Pancreatic islet cell tumors
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Where is GRP produced?
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The vagus nerve branches innervating the G cells
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What does GRP do?
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Stimulates gastrin release from G cells
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What are the two enkephalins?
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Met-enkephalin
Leu-enkephalin |
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Where are the enkephalins produced?
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Nerves in the mucosa and smooth muscle of the GI tract
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What do enkephalins do?
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Stimulate contraction of GI smooth muscle, especially sphincters
Inhibits intestinal secretion of fluid and electrolytes |
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What sphincters are targeted by enkephalins?
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Lower esophageal
Pyloric Ileocecal |
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Why are opiates useful for treating diarrhea?
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They inhibit the intestinal secretion of fluid and electrolytes
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Where in the GI tract would you find skeletal muscle?
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Pharynx
Upper 1/3 of the esophagus External anal sphincter |
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What happens when you depolarize a ring of smooth muscle?
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It contracts, decreasing the diameter of that segment of GI tract
This is the basis for peristalsis |
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What is the difference between tonic and phasic contractions?
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Tonic -- sustained over long periods of time (minutes to hours)
Phasic -- occur over brief periods of time |
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What parts of the GI tract exhibit phasic contractions?
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Esophagus
Gastric antrum Small intestine |
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What parts of the GI tract exhibit tonic contractions?
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Lower esophageal sphincter
Orad stomach Ileocecal sphincter Internal anal sphincter |
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What are slow waves?
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Oscillating membrane potentials inherent to the GI smooth muscle
Occur spontaneously |
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Where do slow waves originate?
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The interstitial cells of Cajal
Serve as the pacemaker for the GI smooth muscle |
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Are slow waves and action potentials the same thing?
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No
However, slow waves determine the pattern of action potentials, and therefore modulate the pattern of contraction Basically, the periodicity of the slow waves determines when action potentials can occur |
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How are slow waves produced?
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There is cyclic opening of Ca channels (which causes depolarization) followed by opening of K channels (which causes repolarization)
Depolarization brings the membrane potential close to threshold, increasing the probability that an action potential will occur Action potentials are produced on top of the background of slow waves, and initiate the contraction of smooth muscle cells |
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What is the frequency of slow waves throughout the GI tract?
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Varies, but for a given region it is constant and characteristic
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How do slow waves and action potentials differ in terms of their regulation?
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Action potentials are influenced by neural and hormonal input; slow waves are not
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What sets the maximum frequency of contractions for a given region of the GI tract?
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Slow wave frequency
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Where is slow wave frequency the lowest? Highest?
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Lowest: stomach (3/min)
Highest: duodenum (12/min) |
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What does chewing do to food?
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Mixes it with saliva to lubricate
Decreases the size of food particles to facilitate swallowing and digestion |
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How does the swallowing reflex work?
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Coordinated in the medulla
Mediated by the vagus and glossopharyngeal nerves |
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What is the sequence of events in swallowing?
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The nasopharynx closes and breathing is inhibited
The laryngeal muscles close the glottis and elevate the larynx Peristalsis begins in the pharynx to propel food toward the esophagus As this happens, the upper esophageal sphincter relaxes so the bolus can pass |
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How does the esophagus maintain a closed environment?
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Sphincters at both ends prevent air from entering (and the lower sphincter prevents gastric reflux)
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What is the intraesophageal pressure?
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Since the esophagus is in the thoracic cavity, intraesophageal pressure = thoracic pressure
Note that this pressure is lower than atmospheric pressure |
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What is the sequence of events in the esophagus after swallowing has been initiated?
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The upper esophageal sphincter relaxes to allow food to pass; it then contracts again to prevent reflux
A primary peristaltic contraction moves the bolus down, and gravity facilitates this A secondary persistaltic contraction occurs The lower esophageal sphincter relaxes to allow food to pass The stomach undergoes receptive relaxation |
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What is a primary peristaltic contraction?
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The creation of high pressure behind a bolus and low pressure in front of it
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What is a secondary peristaltic contraction?
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Clears the esophagus of any remaining food
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What causes the lower esophageal sphincter to relax?
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Parasympathetic stimulation
Mediated by the neurotransmitter VIP |
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What is gastroesophageal reflux and what causes it?
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Heartburn
Can occur if the tone of the lower esophageal sphincter is decreased This allows gastric contents to reflux into the esophagus |
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What causes achalasia?
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Food accumulates in the esophagus
The lower esophageal sphincter does not relax during swallowing to allow food passage |
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How many muscular layers does the stomach have?
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Three:
Inner circular Middle longitudinal Outer circular/oblique |
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What are the three anatomic divisions of the stomach?
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Fundus
Body Antrum |
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What is the orad stomach?
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The fundus and proximal body
This is the region that receives the ingested meal |
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What is the caudad stomach?
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The antrum and distal body
This is the region that contracts to mix food and propel it into the duodenum |
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What type of reflex is receptive relaxation of the stomach?
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Vasovagal
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What is receptive relaxation of the stomach?
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The orad region of the stomach relaxes to accommodate the ingested meal
CCK increases the distensibility of the stomach |
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What is retropulsion?
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A wave of contraction closes the distal antrum
This propels food back into the stomach to be mixed |
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How does the autonomic nervous system modulate the frequency of gastric contractions?
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Parasympathetic -- increases frequency
Sympathetic -- decreases frequency |
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What is the migrating myoelectric complex?
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Even during the fasting state, the stomach contracts every 90 minutes or so to clear the stomach of residual food
This is mediated by motilin |
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How does the stomach empty?
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The caudad region of the stomach contracts, which propels food into the duodenum
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How does the tonicity of stomach contents affect gastric emptying?
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Gastric emptying is fastest when stomach contents are isotonic
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How does fat affect gastric emptying?
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It inhibits it by stimulating the release of CCK
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How does acid in the duodenum affect gastric emptying?
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Inhibits it
H+ receptors in the duodenum signal to the gastric smooth muscle |
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What is the primary function of the small intestine?
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Digestion and absorption of nutrients
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What are the type of contractions observed in the small intestine?
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Segmentation contractions
Peristaltic contractions Gastroileal reflex |
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What are small intestinal segmentation contractions?
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These are contractions that mix the intestinal contents
A section contracts and chyme is propelled forward AND backward This segment then relaxes and the food moves back into that region This causes mixing without any net forward motion of chyme |
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What are small intestinal peristaltic contractions?
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Highly coordinated contractions that propel chyme through the small intestine toward the colon
There is simultaneous contraction behind the bolus and relaxation in front of it, resulting in caudal propulsion |
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What stimulates peristaltic contractions of the small intestine?
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The enteric nervous system
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What is the gastroileal reflex?
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The presence of food in the stomach triggers peristalsis in the ileum, as well as relaxation of the ileocecal sphincter
This allows intestinal contents to be delivered to the colon |
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What factors mediate the gastroileal reflex?
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The extrinsic ANS
Possibly gastrin |
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What is the path of food within the large intestine?
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Cecum
Ascending colon Transverse colon Descending colon Sigmoid colon Rectum Anal canal |
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What are haustra?
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Sac-like segmentation within the large intestine
They are formed by segmentation contractions of the colon |
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How is colonic reflux into the ileum prevented?
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When the proximal colon is filled with fecal material, the ileocecal sphincter contracts
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Where does most colonic water absorption occur?
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The proximal colon
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How does the consistency of poop change as you go along the colon?
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Water is absorbed in the proximal colon
Feces become more solid as they move distally |
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What is responsible for the movement of feces?
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Mass movements of the colon
These movements cause colonic contents to move distally over long distances |
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How many mass movements do we typically experience?
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1-3 per day
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What are the types of contractions observed in the colon?
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Segmentation contractions -- mixing
Mass movements -- forward propulsion |
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What is the sequence of events for defecation?
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As the rectum fills with feces, it contracts and the internal anal sphincter relaxes
When the rectum is about 25% full, you feel the urge, but you can control the tone of the external anal sphincter When it is convenient to defect, you voluntarily relax the external anal sphincter The smooth muscle of the rectum contracts and poop is pushed out Intra-abdominal pressure is increased by expiring against a closed glottis (Valsalva maneuver) |
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What is the rectosphincteric reflex?
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Opening of the internal anal sphincter due to rectal distention
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What is the gastrocolic reflex?
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The presence of food in the stomach increases colonic motility and the frequency of mass movements
Food stretching the stomach produces a rapid parasympathetic component A slower hormonal component is mediated by CCK and gastrin |
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What are some disorders of the frequency of colonic segmentation contractions?
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Irritable bowel syndrome -- increased segmentation contractions; may occur after periods of stress and result in constipation
Diarrhea -- decreased segmentation contractions |
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What is Hirschprung's Disease?
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Also known as megacolon
There is no colonic enteric nervous system in one region This results in constriction of the involved segment There is huge dilation and accumulation of intestinal contents proximal to the constriction Produces severe constipation |
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What is the sequence of events for vomiting?
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A wave of peristalsis begins in the small intestine and moves the GI contents toward the stomach
Gastric contents are pushed into the esophagus Before the upper esophageal sphincter opens, retching occurs When/if you generate enough pressure to open the upper esophageal sphincter, vomiting occurs |
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What are the neurological regions involved in vomiting, and what triggers them?
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Vomiting center of the medulla: tickling the back of the throat, gastric distention, vestibular stimulation (motion sickness)
Chemoreceptor trigger zone in the fourth ventricle: stimulated by emetics, radiation, and vestibular stimulation |
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What are the functions of saliva?
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Initial starch digestion by amylase
Initial triglyceride digestion by lingual lipase Lubrication of food with mucous Protection of the mouth and esophagus by diluting and buffering ingested food |
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What is the chemical composition of saliva?
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Water
High K and HCO3 Low Na and Cl Overall hypotonic Amylase, lingual lipase, kallikrein |
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How does the chemical composition of saliva change with flow rate?
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As flow rate increases
Na, HCO3, Cl concentration increase Osmolarity increases K concentration decreases |
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When is saliva similar to the composition of plasma?
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At high salivary flow rates (up to 4 ml/min)
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What are the salivary glands?
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Parotid
Submandibular Sublingual |
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What is the structure of a salivary gland?
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There is an acinus (blind end) that is lined with acinar cells, which secrete the initial saliva
A branching duct system of columnar epithelium modifies the secretion |
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How is saliva ejected into the mouth?
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Myoepithelial cells lining the acini and ducts contract to expel the glandular contents
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What is the function of the salivary acinus?
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Produces an initial saliva that has a composition similar to plasma
This initial saliva is isotonic and has the same electrolyte concentrations as plasma |
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What is the function of the salivary duct?
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Modification of the initial saliva
Na and Cl are reabsorbed K and HCO3 are secreted Saliva becomes hypotonic because the ducts are relatively impermeable to water |
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How does aldosterone affect salivary composition?
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It acts upon the ductal cells to increase Na reabsorption and K secretion, just like in the distal tubule of the nephron
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Why is saliva most like plasma at high flow rates?
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There is less time for absorption and secretion to occur, so Na, K, and Cl concentrations will be the same as in plasma
This is not true for HCO3, which is selectively stimulated when salivation is stimulated |
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What controls saliva production?
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Parasympathetic and sympathetic stimulation
GI hormones do NOT affect salivation |
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What is the effect of parasympathetic stimulation upon salivation flow rate? Sympathetic stimulation?
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They BOTH increase flow rate, but parasympathetic stimulation is more important
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What is the parasympathetic innervation to the salivary glands?
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CN VII and IX
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How does parasympathetic stimulation facilitate salivation?
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Transport processes in the acinar and ductal cells are increased
Vasodilation is induced |
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What is the parasympathetic signaling pathway for the induction of salivation?
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Activation of muscarinic receptors on acinar and ductal cells
IP3 is produced Intracellular [Ca] increases |
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Why does atropine cause dry mouth?
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It is an anticholinergic drug, and cholinergic signaling stimulates salivation
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How does sympathetic stimulation facilitate salivation?
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Increases the production of saliva
Promotes the growth of salivary glands |
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What is the sympathetic signaling pathway for the induction of salivation?
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Activation of B-adrenergic receptors on acinar and ductal cells
cAMP concentration increases |
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What environmental factors increase saliva production?
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Food in the mouth
Smell Conditioned reflexes Nausea These things all act through activation of the parasympathetic nervous system |
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What environmental factors decrease saliva production?
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Sleep
Dehydration Fear Anticholinergic drugs These things all act through the inhibition of the parasympathetic nervous system |
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What are the secretory cells of the stomach?
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Parietal cells: located in the body, secrete HCl and intrinsic factor
Chief cells: located in the body, produce pepsinogen G cells: located in the antrum, produce gastrin |
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What is the mechanism of gastric acid secretion?
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In the parietal cells, carbonic anhydrase catalyzes the conversion of CO2 and water to H and HCO3
H is secreted into the stomach lumen through the H-K ATPase Cl is also secreted along with H, so the final secretion product is HCl The HCO3 is absorbed into the bloodstream in exchange for Cl via the Cl-HCO3 exchanger |
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How does omeprazole work?
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It inhibits the H-K ATPase and blocks H secretion by the parietal cells
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What is the alkaline tide?
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As acid is secreted into the stomach, base is absorbed into the bloodstream, which causes plasma pH to increase
This HCO3 will eventually be secreted by the pancreas |
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How does vomiting contribute to metabolic alkalosis?
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Gastric acid never reaches the small intestine
Therefore, there is no stimulus for pancreatic HCO3 secretion The arterial blood becomes alkaline |
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What is the DIRECT pathway for vagal stimulation of gastric acid secretion?
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The vagus nerve innervates the parietal cells and stimulates them
ACh binds to M3 muscarinic receptors IP3 is generated and intracellular [Ca] increases |
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What is the INDIRECT pathway for vagal stimulation of gastric acid secretion?
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The vagus nerve innervates G cells
Gastric secretion is stimulated The neurotransmitter is GRP |
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How does atropine inhibit gastric acid secretion?
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It is a cholinergic muscarinic antagonist, so it blocks the direct vagal pathway
However, it has no effect upon the direct pathways |
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What effect would a vagotomy have upon parasympathetic stimulation of gastric acid secretion?
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It would eliminate both the direct and the indirect pathways
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What is the pathway for gastrin stimulation of acid secretion?
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Gastrin interacts with the CCK8 receptor on parietal cells
Generates IP3/Ca |
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What is the pathway for histamine stimulation of acid secretion?
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Histamine binds H2 receptors on the parietal cell membranes
Adenylyl cyclase is activated via a Gs protein cAMP is produced |
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How does cimetidine work?
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Blocks the H2 receptor so histamine cannot stimulate acid secretion
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What is potentiation?
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When the response to two simultaneous stimulants is greater than the sum of responses to the stimulants given alone
This means that low concentrations of stimulants given together can produce maximal effects |
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What factors inhibit gastric acid secretion?
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Low pH (less than 3.0)
Somatostatin Prostaglandins |
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How does acidic pH inhibit gastric acid secretion?
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As acid is produced, the pH of the stomach decreases
When it goes below 3.0, a negative feedback loop inhibits further acid production |
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How does somatostatin inhibit gastric acid secretion?
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Direct pathway -- binds to receptors on the parietal cells that are coupled to adenylyl cyclase by a Gi protein, which decreases cAMP levels (opposes the histamine pathway)
Indirect pathway -- inhibits release of histamine and gastrin |
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How do prostaglandins inhibit gastric acid secretion?
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They activate a Gi protein, which inhibits adenylyl cyclase and decreases cAMP levels
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What is peptic ulcer disease?
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Ulcerative lesions of the gastric or duodenal mucosa
Can occur when the mucous barrier is breached or when there is excessive production of H and pepsin Protective factors: mucous, HCO3, prostaglandins, mucosal blood flow, growth factors Damaging factors: H, pepsin, H pylori, NSAIDs, stress, smoking, alcohol |
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How do gastric ulcers impact gastric acid secretion?
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Acid secretion is decreased because the secreted H leaks back through the damaged mucosa and inhibits its own production via a negative feedback loop
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How do gastric ulcers impact gastrin production?
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Gastrin secretion is increased because low acid concentrations stimulates the G cells
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What bacteria is a major cause of gastric ulcers?
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Helicobacter pylori
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How does H pylori survive in the acidic environment of the stomach?
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It produces urease, which converts urea to NH3
This establishes a zone of neutrality in the otherwise-acidic stomach |
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How does H pylori cause gastric ulcers?
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Colonizes the gastric mucosa
Releases damaging cytotoxins |
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What is the diagnostic test for H pylori infection?
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You drink a solution of 13C-urea
If you have H pylori, it will be converted to 13CO2 by bacterial urease, and this can be measured in the expired air |
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How do duodenal ulcers impact gastric acid secretion?
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Acid secretion is increased
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How do duodenal ulcers impact gastrin production?
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Gastrin production in response to a meal is increased, but the baseline level may be normal
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How does H pylori infection in the duodenum alter GI hormonal signaling?
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Somatostatin secretion is inhibited, so gastric acid secretion is stimulated
Intestinal absorption of bicarbonate is inhibited |
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What is Zollinger-Ellison syndrome?
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A gastrin-secreting tumor of the pancreas causes increased acid secretion
Acid secretion continues unchecked because the gastrin secreted by the tumor is not subject to acid-mediated negative feedback |
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Why is cimetidine such a good acid inhibitor?
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It blocks histamine stimulation
It also blocks histamine's potentiation of ACh |
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What kinds of things are found in pancreatic secretion? (in general)
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HCO3 to neutralize the acidic chyme that is delivered to the duodenum
Digestive enzymes |
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How does the composition of pancreatic secretion compare to plasma?
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Same Na and K concentrations as plasma
Much higher HCO3 Much lower Cl Isotonic Contains lipase, amylase, and proteases |
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How does the composition of pancreatic secretion change with flow rate?
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At low flow rates, the pancreatic juice is made mostly of Na and Cl
At high flow rates, the secretion is mostly Na and HCO3 Pancreatic secretions are isotonic, regardless of flow rate |
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What do the acinar cells of the pancreatic glands do?
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They produce the initial pancreatic secretion, which is mostly Na and Cl
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What do the ductal cells of the pancreatic glands do?
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Secrete HCO3 and absorb Cl via Cl-HCO3 antiport in the luminal membrane
The ducts are permeable to water, so water flows in to increase the volume and make the secretion isosmotic |
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What does secretin do?
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Acts upon the pancreatic ductal cells to increase HCO3 secretion
Thus, when acid enters the duodenum, HCO3 is released into the lumen to neutralize it |
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What second messenger does secretin use?
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cAMP
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How does CCK act upon the pancreas?
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Causes the acinar cells to increase production of amylase, lipase, and proteases
Potentiates the effect of secretin on the ductal cells |
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What second messenger does CCK use?
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IP3 and increased intracellular Ca
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How does ACh affect pancreatic secretion?
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ACh is released in response to acid and partly digested food in the duodenal lumen
Stimulates enzyme secretion by the acinar cells Potentiates the effect of secretin on HCO3 secretion |
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What is cystic fibrosis?
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A disorder of pancreatic secretion
A mutation in the CFTR gene causes a defect in Cl channels Associated with pancreatic enzyme insufficiency, which results in malabsorption and steatorrhea |
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What are the main components of bile?
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Bile salts
Phospholipids Cholesterol Bile pigments (bilirubin) |
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How do bile salts aid in absorption?
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They are amphipathic molecules, so they orient themselves around lipid molecules and keep them dispersed in micelles
This is known as emulsification |
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What are micelles?
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Above a critical micellar concentration, bile salts form micelles
The bile salts are positioned on the outside of the micelle with their hydrophilic portions dissolved in the aqueous luminal fluid Free fatty acids and monoglycerides are present inside the micelle, and have been essentially solubilized for intestinal absorption |
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Where is bile produced?
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The liver
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Where is bile stored?
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It drains to the gallbladder via the hepatic ducts, and is stored/concentrated there until release
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What are choleretic agents?
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Things that stimulate the formation of bile
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How is bile formed?
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Hepatocytes synthesize primary bile acids (cholic acid and chenodeoxycholic acid) from cholesterol
In the intestine, the bacteria convert some primary bile acid to secondary bile acids (deoxycholic acid and lithocholic acid) Bile acids are conjugated with glycine or taurine to form bile salts (taurocholic acid, etc) Electrolytes and water are added to the bile During the interdigestive period, the gallbladder is relaxed and fills with bile. The sphincter of Oddi is closed |
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When is new bile made?
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Some bile is reabsorbed, and some is lost in the feces
New bile is made to compensate for fecal loss |
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How does the gallbladder concentrate bile?
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Isosmotic absorption of solutes and water
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What hormones mediate contraction of the gallbladder?
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CCK
ACh |
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How do secreted bile acids circulate back to the liver?
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The terminal ileum has an Na-bile cotransporter, which is secondary active
Since bile acids aren't recirculated until the terminal ileum, they are present for maximal lipid absorption throughout the upper small intestine |
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How does ileal resection affect bile recirculation?
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Bile acids are no longer recirculated to the liver and are secreted in the feces
This depletes the bile acid pool and impairs fat absorption, which causes steatorrhea |
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What is the intestinal brush border?
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The intestinal mucosa has villi, and the villi have microvilli; these microvilli are the brush border
This increases the absorptive surface area |
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What types of sugars are absorbed
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Monosaccharides
Therefore, carbohydrates must be digested to monosaccharides before absorption can occur |
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What are the three monosaccharides that can be absorbed?
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Glucose
Galactose Fructose |
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What does amylase do?
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Hydrolyzes the 1,4-glycosidic bonds in starch
This gives maltose, maltotriose, and branched structures known as alpha-limit dextrins |
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Where is amylase found?
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Saliva and pancreatic secretion
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Where are maltase, a-dextrinase, and sucrase found?
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In the intestinal brush border
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What do maltase, a-dextrinase, and sucrase do?
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They digest the oligosaccharide amylase digestion products to glucose monomers
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What does lactase do?
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Cleaves lactose to glucose and galactose
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What does trehalase do?
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Cleaves trehalose to glucose
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What does sucrase do?
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Cleaves sucrase to glucose and fructose
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How are glucose and galactose absorbed?
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They are transported into the cells by Na-dependent transport via SGLT1
The sugar is transported uphill and Na is transported downhill The sugar is then transported into the blood by facilitated diffusion using GLUT2 The Na-K ATPase maintains the Na gradient |
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What would happen to glucose and galactose absorption if you poisoned the Na-K ATPase?
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It would be abolished because it requires the Na gradient established by the ATPase
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How is fructose absorbed?
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Transported by facilitated diffusion (GLUT5)
Therefore, it cannot be absorbed against a concentration gradient |
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What is lactose intolerance?
|
Brush border lactase doesn't work
You cannot hydrolyze lactose to glucose and galactose Nonabsorbed lactose and water remain in the lumen of the GI tract and cause osmotic diarrhea |
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What do endopeptidases do?
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Degrade proteins by hydrolyzing interior peptide bonds
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What do exopeptidases do?
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Hydrolyze one amino acid at a time from the C' of proteins and peptides
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What is the zymogen precursor of pepsin?
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Pepsinogen
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What activates pepsinogen to pepsin?
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Gastric acid
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What is the optimum pH for pepsin's function?
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1-3
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What happens to pepsin when pH exceeds 5?
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It becomes denatured
Therefore, as bicarbonate is secreted into the intestine, the pH increases and pepsin is inactivated |
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What are the proteases produced by the pancreas?
|
Trypsin
Chymotrypsin Elastase Carboxypeptidase A Carboxypeptidase B |
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What catalyzes the conversion of trypsinogen to trypsin?
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Enterokinase, a brush border enzyme
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How are the pancreatic proteases activated?
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Trypsinogen is activated to trypsin
Trypsin activates the rest of the zymogens (including trypsinogen) |
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How are the pancreatic proteases inactivated?
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They will eventually degrade each other, and are absorbed along with dietary proteins
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What sorts of protein digestive products can be absorbed?
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Single amino acids
Dipeptides Tripeptides |
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How are free amino acids absorbed?
|
Na-dependent amino acid cotransport occurs across the luminal membrane
The amino acids are then delivered to the blood by facilitated diffusion This diffusion utilizes four separate carriers for neutral, acidic, basic, and imino amino acids |
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How are dipeptides and tripeptides absorbed?
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H-dependent cotransport of peptides occurs across the luminal membrane
The peptides are hydrolyzed to amino acids by cytoplasmic peptidases Amino acids are delivered to the blood by facilitated diffusion |
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Is the absorption of free amino acids faster or slower than the absorption of di and tripeptides?
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Slower
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Where does lipid digestion take place?
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Stomach
Small intestine |
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How are lipids digested in the stomach?
|
Mixing breaks lipids into droplets, which increases the surface area for digestion by pancreatic enzymes
Lingual lipase digests some TAGs to monoglycerides and fatty acids CCK slows gastric emptying, so there is plenty of time for digestion to proceed to completion |
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How are lipids digested in the small intestine?
|
Bile acids emulsify lipids to increase the surface area for digestion
Pancreatic lipases hydrolyze lipids to fatty acids, monoglycerides, cholesterol, and lysolecithin The hydrophobic digestion produces are solubilized by bile acids in micelles |
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What are the pancreatic lipases?
|
Pancreatic lipase
Cholesterol ester hydrolase Phospholipase A2 |
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How are lipids absorbed?
|
Micelles bring the products of lipid digestion to the absorptive surface of the small intestine
Fatty acids, monoglycerides, and cholesterol diffuse across the luminal membrane into the cells These digestion products are then re-esterified to glycerol, cholesterol, and phospholipids Packaged with apoproteins into chylomicrons Chylomicrons are transported out by exocytosis They go into the lymph vessels and are added to the bloodstream via the thoracic duct |
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What is abetalipoproteinemia?
|
Lack of apoprotein B
You can no longer transport chylomicrons out of the intestinal cells |
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What is pancreatic disease?
|
Pancreatitis, cystic fibrosis
The pancreas can't produce enough digestive enzymes for lipid digestion |
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What is the primary symptom of lipid malabsorption?
|
Steatorrhea
|
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How does gastrin hypersecretion contribute to lipid malabsorption?
|
Acid secretion increases
Duodenal pH decreases This inactivates pancreatic lipase |
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How does ileal resection contribute to lipid malabsorption?
|
Bile acids do not recirculate to the liver
This depletes the bile acid pool |
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How does bacterial overgrowth contribute to lipid malabsorption?
|
This can lead to deconjugation of bile acids
The bile acids are absorbed too early in the upper small intestine Now bile acids are not present throughout the small intestine to aid in lipid absorption |
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How do the number of intestinal cells affect lipid absorption?
|
If you don't have enough cells, obviously you won't have enough absorption
Somehow this is relevant in the case of tropical sprue |
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How does abetalipoproteinemia contribute to lipid abnormality?
|
You can no longer form chylomicrons
|
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How do electrolytes and water cross the intestinal epithelium?
|
Cellular route -- crosses the cell membrane
Paracellular route -- moves between cells, across tight junctions |
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How are epithelial cells attached to each other at the luminal membrane?
|
Tight junctions
|
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How does the permeability of epithelial tight junctions vary throughout the GI tract?
|
They can be tight/impermeable, such as in the colon
They can also be leaky/permeable, such as in the small intestine and gallbladder |
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How is Na absorbed across the apical membrane of the small and large intestine?
|
It always moves down its electrochemical gradient via:
Passive diffusion through Na channels Na-glucose cotransport Na-amino acid cotransport Na-Cl cotransport Na-H exchange |
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|
What Na transport mechanisms are the most important in the small intestine?
|
Na-glucose cotransport
Na-amino acid cotransport Na-H exchange |
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|
What Na transport mechanisms are most important in the colon?
|
Passive diffusion via Na channels
|
|
|
Where in the GI tract does aldosterone stimulate Na reabsorption?
|
In the colon, via Na channels
|
|
|
How is Na transported out of the intestinal enterocytes?
|
Na-K ATPase
|
|
|
How does Cl absorption accompany Na absorption throughout the GI tract?
|
Passive paracellular diffusion
Na-Cl cotransport Cl-HCO3 exchange |
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|
How is dietary K absorbed?
|
It is absorbed in the small intestine via passive paracellular diffusion
|
|
|
How is K secreted in the colon?
|
Stimulated by aldosterone
|
|
|
How does diarrhea contribute to hypokalemia?
|
The increased flow rate increases K secretion
Excessive K is lost in the feces |
|
|
How is water absorbed in the GI tract?
|
Water absorption is secondary to solute absorption
It is isosmotic in the small intestine and gallbladder In the colon, water permeability is low, so the feces may be hypertonic |
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|
How are electrolytes secreted into the GI lumen?
|
Electrolytes are transported from the blood to the lumen
The secretory mechanisms are found in the crypts |
|
|
Where in the intestinal architecture are the electrolyte absorptive mechanisms found?
|
In the villi
|
|
|
What electrolytes are secreted in the intestine?
|
Cl is the primary secreted ion
Na passively follows Na Water follows NaCl |
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|
How is Cl secreted into the intestine?
|
Transported through Cl channels that are regulated by cAMP
|
|
|
How does Vibrio cholerae cause diarrhea?
|
Produces cholera toxin
This toxin catalyzes ADP-ribosylation of the alpha subunit of the Gs protein coupled to adenylyl cyclase This permanently activates AC Intracellular cAMP increases and the Cl channels in the luminal membrane open Na and water follow Cl into the lumen, leading to secretory diarrhea |
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|
Besides Vibrio cholerae, what bacterium can also commonly cause diarrhea (and via a similar mechanism)?
|
E coli
|
|
|
How are the fat-soluble vitamins absorbed?
|
They are incorporated into micelles and are absorbed with other lipids
|
|
|
What are the fat-soluble vitamins?
|
A, D, E, and K
|
|
|
How are the water-soluble vitamins (except vitamin B12) absorbed?
|
Na-dependent cotransport (usually)
|
|
|
How is vitamin B12 absorbed?
|
Forms a complex with intrinsic factor
This complex binds a receptor on the ileal cells and is reabsorbed there |
|
|
How does gastrectomy cause pernicious anemia?
|
You are removing the parietal cells, which produce intrinsic factor
B12 injections are required to prevent anemia |
|
|
How is Ca absorbed?
|
Depends upon the presence of adequate amounts of the active form of vitamin D (1,25-dihydroxycholecalciferol)
Vitamin D is made in the kidney Vitamin D induces the synthesis of the intestinal Ca-binding protein calbindin D-28K |
|
|
What causes rickets and osteomalacia?
|
Vitamin D deficiency
Chronic renal failure |
|
|
How is iron absorbed?
|
Absorbed as heme iron (bound to Hb or myoglobin) or as free Fe2+
In the intestine, heme iron is degraded and Fe2+ is released Free Fe2+ binds apoferritin and is transported into the blood In the blood, Fe2+ circulates bound to transferrin, which delivers it to the liver Iron is then transported from the liver to the bone marrow for hemoglobin synthesis |
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|
What is the most common cause of anemia?
|
Iron deficiency
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