GI 1 Flashcards
Primary and auxillary structures of GI system
Pharynx
- Plays a role in breathing air
- Also plays a role in swallowing food (along with epiglottis)
Switch from skeletal to smooth muscle in GI system
- Skeletal muscle in mouth, tongue, back of throat, under voluntary & reflexive control
- In upper part of esophagus, muscle switches to smooth (not directly innervated
- Smooth muscle all the way down
Overview of control of smooth muscle
- Local neurons
- Modulated by symp and parasymp innervation
- Modulated by paracrines and endocrine factors
The smooth muscle from the top of the esophagus, all the way down to the anus, is under ___ nervous system control
Autonomic
External anal sphincter
Under conscious control
Auxillary structures are connexted to the GI system by ___
Ducts
Sphincters in the GI system
Open to let food through and close to prevent backwards movement
Which sphincter prevents backflow of contents of the stomach into the esophagus?
Lower esophageal sphincter
What does the pyloric valve control?
Emptying of stomach contents into SI (+juices from liver and pancreas)
Graph showing big picture of GI system
57 mins
Protection of stomach and small intestine from damage
- Only secrete acid when food is present
- Compartmentalization (limitation of acid to one portion)
COMMUNICATION: neural and hormonal - Secrete precursors (as opposed to active enzyme)
Nutrients
Anatomy of the gut: stomach and intestine (this most closely resembles small intestine)
- Large SA (villi and microvilli)
- Microenvironment created by tightly-folded membrane called brush border
Nervous control
- Neurons can activate smooth muscles or secretory cells
- The secretions can be exocrine or endocrine (signaling molecules)
- Stimulated by changes in chemical environment (pH, presence of digestion, osmolarity) and stretch
- Input from the CNS - can impact sympathetic and parasympathetic neurons to regulate motility and secretion (para increases, symp inhibits)
Two branches of nervous control
- Sensory signals sent from the GI tract up to the brain to reinforce what’s happening in the GI
- Other input that’s only available at the brain (sight, smell of food)
Sympathetic and parasympathetic axons primarily innervate ___
ENS neurons
(In some cases they can directly innervate smooth muscle and secretory cells)
What is the nucleus of the solitary tract?
The major integration center for feeding in the brainstem
Vomit reflex (mediated by NOST)
- Closes off the pyloric valve, so nothing goes into the small intestine
- Relaxes the smooth muscles in the walls of the stomach, so it’s flaccid
- Relaxes the lower and upper esophageal sphincters
- Begins the retching mechanism of the skeletal muscle, which involves squeezing the abdominal muscles and diaphragm
- This pushes up on the stomach, squeezing the flaccid stomach
Functions of NOST
- Receives visceral sensory (ENS) and somatic sensory input
- Coordinates visceral motor reflexes
- Affects hypothalamus and release of hormones
- Affects behavior associated with feeding
Labeled diagram of stomach
Anatomy of stomach
- Two sphincters: lower esophageal and pyloric
- The pyloric gland area that forms the endocrine function of the stomach, releasing hormones into the blood, is at the bottom, near the pyloric sphincter
Motility of stomach
- Stomach squeezes in a peristaltic wave to the pyloric area
- If the pyloric valve is not open, there will be aggressive regurgitation
- The ridges of the stomach mechanically break apart food
Gastric gland
- The cells on the side secrete into the lumen of the duct, and the duct empties into the lumen of the stomach
- The cells at the opening of the gastric glands secrete a mucus to protect themselves from the acidic environment in the stomach
- This would clog up the duct, but as you actively secrete solutes, salt, and water, the volume/pressure in the duct builds up and every once in a while there’s a secretion into the stomach
- Then, the mucus layer closes again to protect the cells deeper down
What do parietal cells secrete?
- Hydrochloric acid (HCL)
- Intrinsic factor
Functions of HCL
- Activates pepsin
- Kills bacteria
What cells secrete pepsin?
Chief cells
What do chief cells secrete?
- Pepsin(ogen)
- Gastric lipase
Pepsinogen
- It is a longer peptide than pepsin and it is inactive
- It goes out into the lumen and gets digested into pepsin
- It can then digest proteins
What is the function of pepsin?
Digests proteins
What is the function of gastric lipase?
Digests fats
The stomach releases ___ liters of secretions each day
1.5
What do mucus cells secrete?
Mucus and bicarbonate, which protects the environment in the duct
Exocrine cells in stomach
- Mucus cells
- Parietal cells
- Chief cells
Endocrine cells in stomach
- G cells
- D cells
- Enterochromaffin-like cells
What do G cells secrete?
Gastrin
Function of gastrin
Stimulates gastric acid secretion
What do D cells secrete?
Somatostatin
Function of somatostatin
Inhibits gastric acid secretion
What do Enterochromaffin-like cells secrete?
Histamine
Function of histamine
Stimulates gastric acid secretion
Table of stomach cell functions
Paracrine function
- E.g. D cells
- Secretion into stomach from nearby cells, inside body
What stimulates somatostatin release?
- Too much acid in stomach
- D cells will secrete somatostatin
What stimulates G cells to release gastrin?
Acetylcholine, peptides, and amino acids
What stimulates secretion of mucus?
Irritation of mucosa
Secretion of HCl
20:00
How do antihistamines affect the stomach?
Blocks release of gastric acid, which can cause GI side effects
What are the three phases in the control of gastric secretion and motility?
- Cephalic
- Gastric
- Intestinal
Cephalic, gastric, and intestinal phases to the control of gastric secretion and motility
- Location of stimuli define the phase
- All responses are at the level of the stomach (gastric)
- Motility = smooth muscle depolarization and subsequent contraction
- Secretion is both exocrine (into lumen, outside body), and paracrine (nearby cells, inside body)
- Categories of effectors include:
-Autonomic NS (symp and parasymp)
-Enteric NS
-Paracrines and endocrines (hormones)
List of pertinent hormones and paracrines
GIP
- GIP was originally named according to the first observed effect, inhibiting parietal cells in stomach.
- Subsequent research has confirmed that it does inhibit HCl secretion to a small degree, but its major target are Beta cells in pancreas prompting a name change to Glucose-dependent insulinotropic polypeptide.
- When glucose is present in lumen of GI tract GDIP is released and triggers Beta cells in the pancreas to secrete insulin into bloodstream.
What is a primary function of GIP (what it was named for)?
Releases insulin, increases the number of beta cells over time
Which cells release which hormones? Know the ‘dogma’ of certain cells release certain peptide hormones but also realize the story is a bit more complex.
“One of the most interesting findings from this set of papers was the identification of other secreted proteins coexpressed with somatostatin. Indeed, transcripts of propancreatic polypeptide (ppy),peptide YY(pyy), proamylin (iapp),gip,cck,gastrin, andghrelinwere all found in somatostatin(+) cells, with the first 3 peptides enriched about 100-fold (11) to more than 1000-fold (10) compared with somatostatin(−) cells. This finding lends substantial credence to the view of coproduction of multiple regulatory peptides within the same enteroendocrine cell types, as opposed to the older dogma of one cell type-one hormone (13,–15).”
Cephalic phase
- Smell, taste, thought of food (all stimuli in brain) trigger gastric secretion (exocrine & endocrine) and motility (contraction of smooth muscle)
- Directly increases activity of the enteric NS
- Gastric secretion and motility driven by increased parasympathetic and decreased sympathetic to the enteric NS (brain uses visceral motor component)
Gastric phase
- Gastrin causes histamine release and directly stimulates parietal cell
- G cells release gastrin and are stimulated by the vagus nerve (parasymp innervation of gut)
- Also involved inhibitory control: presense of acid is sensed by and stimulates the release of pepsinogen by chief cells, which then goes into the stomach to be cleaved into the active pepsin
- Somatostatin also plays an inhibitory role (next flashcard)
Negative feedback of somatostatin in gastric phase
If there’s too much acid, D cells release somatostatin, which puts the breaks on acid and gastrin secretion (which promotes acid secretion) and chief cells
There is always a ___ response throughout the GI tract
Stretch-receptor
Intestinal phase
- Chyme enters the initial segment of the small intestine
- In this segment, and all along, it’s being ‘tasted’, and a response will be generated
- The SI picks up secretions of bile from the liver, secretions from the pancreas with digestive enzymes
- Motility is impacted
What is the net output from the stomach to the small intestine?
What does presence of food in the small intestine do to the stomach? (blue arrows on diagram mean inhibition)
- Given that the stomach can store a lot of food and the opening into the SI is quite small, you can’t empty all of the stomach contents into the SI at once - it has to be controlled
- Most of the feedback that the small intestine sends to the stomach is inhibitory
- It tells the stomach to slow down so that chyme is not passed through the SI too quickly without every calorie and nutrient being extracted
- Chyme comes into the SI, and this is sensed by the ENS
Most of the feedback that the small intestine sends to the stomach is ___
Inhibitory
Chyme comes into the small intestine, and this is sensed by the ___
Enteric NS
What’s in the chyme?
Acid, fats, carbs, protein, hyper-osmotic solution
Fats primarily affect___
CCK
More info on GIP?
51 mins
Functions of CCK
- Inhibits stomach movements and acid secretion
- Primary function: goes to gall bladder and stimulates the release of bile
Bile
Contains bile salts that break up large globules of fat floating inside of water into smaller globules of fat, creating surface area for enzyme action
Effects of the presence of acid in the SI
- Causes the release of secretin
- Inhibits secretion of acid in the stomach
- Goes to the pancreas and causes the secretion of bicarbonate
Pancreatic secretions
- They reverse what happens in the stomach
- They secrete bicarbonate (alkaline) and reabsorb acid into the bloodstream
- The acid going back into the bloodstream kills the alkaline wave caused by the stomach (?)
- The base going into the lumen of the digestive tract neutralizes the acid
pH in stomach vs. SI
- In the stomach, an acidic pH makes sense because pepsin and lipase work well at a low pH
- The digestive enzymes secreted into the small intestine actually operate better at a more neutral pH, so chyme is gradually neutralized as the pancreas is stimulated to secrete more bicarbonate
Hyper-osmotic solution (component of chyme)
Falls out of breaking big molecules into a lot of small molecules
Diagram showing another way of looking at the intestinal phase
58:18
Liver
- Bilirubin is produced in the breakdown of RBCs and it gives bile its greenish-yellowish color
- Bile salts for emulsification of lipids
Pancreas
- Has both endocrine and exocrine cells
- Exocrine: secretes digestive enzymes for lipids, proteins, and carbohydrates (precursors to enzymes that are cleaved when they enter the SI)
- Released into the duodenum (initial segment of SI)
- Mixed with secretions from common bile duct
Blockage in pancreatic duct
- Can cause irreparable harm in a few hours
- If you block the duct but still secrete the precursor enzymes, they’ll accumulate in the ducts of the pancreas
- If they sit there long enough, they’ll autocleave into the active enzyme and start digesting whatever’s around them
- First, that’s cells that line the wall of the pancreatic duct, and then further out into the pancreas
- The pancreas can digest itself within a day
Endocrine cells of pancreas
- Alpha: glucagon
- Beta: insulin
How do pancreatic secretions with inactive forms of the enzymes get activated?
Enterokinases in brush border of small intestine
Enterokinases in brush border of small intestine
1.Pancreas secretes inactive proenzymes that are activated in the lumen of the GI tract
2.Trypsinongen is cut into shorter protein Trypsin by brush border enzyme enteropeptidase
3.Trypsin, now an active enzyme (peptidase), activates remaining proenzymes by cutting peptide bonds
- Proteins, Carbs and Fats are now digested in lumen of small intestine by activated enzymes.
How does the pancreas secrete bicarbonate?
- Carbonic anhydrase forms bicarb and H+
- Sodium and protons are exchanged in the basolateral membrane (right side)
- The bicarb is exchanged with chloride in the apical membrane (left)
- Sodium ions come in and the protons come out (secondary active transport)
- The protons coming out neutralize the alkaline wave
- The basic solution in the lumen of the pancreatic duct will go out and neutralize the chyme coming out of the stomach
Large intestine
- Whatever enters the large intestine is indigestible
- Also bacteria that populate the SI and LI that die and slough off
- In the small intestine there are bacterial colonies that can break down fiber (to a certain degree), which also nourishes the bacteria
- Fiber adds bulk to what moves through the GI tract
- The bacteria can liberate some nutrients that were absorbed in the large intestine (?)
What is feces composed of?
- Dead bacteria
- Fiber that wasn’t digested
- Bilirubin (brown color)
Appendix
People with an appendix are better at recovering from diarrhea more quickly
Probiotic research/industry -very confusing mix of substantiated and unsubstantiated claims/theories
- Probiotics - “…live microorganisms that, when administered in adequate amounts, confer a health benefit on the host.” International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. 2014.
- Probiotic Effector Molecules – putative molecules of action which convey benefit to host.
Lactobacillus and Bifidobacterium strains have demonstrated benefits to host
Putative Benefits of microbiome that are supported by literature
- Compete out harmful microorganisms
- Strengthen the epithelial barrier (tight junctions)
- Communicate with Immune System (serotonin plays a key role in this)
- Activate hormonal signaling
- Communicate with the central nervous system signaling (e.g. intestinal TRPV channels)
Gut-Brain Axis
- Gut and Brain sense changes in environment and effect each other via the immune system
- Bi-directional effects are present (e.g. gut to brain and brain to gut)
- Chronic inflammation of gut and brain are key elements in dysfunction
- Mouse studies provide the most direct connection between gut and brain
- GBA is thought to play a role in several human diseases/disorders including inflammatory bowel disease (e.g. -Parkinson’s disease, autism spectrum disorder, multiple sclerosis)
C. List the cells in the stomach that have receptors for somatostatin. (3pts)
- G cells
- Parietal cells
- Chief cells
