GI Physiology Overview Flashcards
Alimentary Canal
Provides a large surface area for the exchange of nutrient, salt, and water between the outside world and internal environment.
Hepat(o)
Liver
Esoph(a)
Esophagus
Gastr(o)
Stomach
Ileo
Small intestine
Colo
Large intestine
Cholecyst
Gallbladder
Proct(o)
Rectum
Enter(o)
Intestine
What are the conventional gross structures of the Gastro-intestinal system?
- Upper: Oral Cavity, Esophagus, Stomach, Small Intestine
- Lower: Large intestine
What are the components of the bowel/gut?
- Small intestine: Duodenum, jejunum, ileum
- Large intestine: appendix, colon, rectum, and anus
What are the accessory organs of the GI system?
- Salivary glands (parotid, submandibular, sublingual)
- Exocrine pancreas
- Liver - hepatic system
- Gallbladder - Biliary system
What are the roles of sphincters?
Regulate movement in gastrointestinal tract and allow some compartments to act as reservoirs.
Which sphincters can you voluntarily control?
- Upper esophageal sphincter
- External anal sphincter
What ar the four major layers of the GI wall?
- Mucosa
- Submucosa
- Muscularis externa
- Serosa
What is the mucosa?
Interface between body and environment
What is the function of the mucosa?
Secretion, Absorption, Barrier, and Immunologi protection. Has specialized folds to increase surface area.
Where are Enterocytes? What are their components?
Small Intestine
-Lumen, villus, crypt
What are colonocytes? What are their components?
Colon
-Lumen, surface, crypt
Unlike most other cell types, GI epithelial cells…
…undergo constant renewal
How often does apoptosis occur in GI epithelial cells?
Every 3-6 days after which the cell is shed into the lumen.
What does apoptosis in GI epithelial cells prevent?
Prevents the accumulation of mutations due to toxin exposure
What are located at the base of the GI epithelial cell crypts? What do they do?
Stem cells.
-Divide, differentiate and migrate to tips of the villi
What is the Diverticulum?
Single pouch protruding from alimentary tract. Usually false not true.
What is Diverticulosis?
Multiple diverticula
What is Diverticulitis?
Impacted with feces, inflamed, painful if blood vessel is eroded hemorrhage.
Mucus
Viscous, hydroscopic gel secreted by goblet cells (mucus is the noun, mucous is the adjective)
What is Mucin?
Protein monomers combined into complexes by disulfide links, 2 layers in the stomach and colon, 1 layer in small intestine
What is the function of glycosylation?
Protects the protein core from proteases and carbohydrate side chains attract water forming a gel.
What are enterocytes coated with?
Transmembrane mucins.
What are the four basic processes facilitating caloric uptake?
- Digestion
- Absorption
- Secretion
- Motility
Define digestion:
Mechanical and chemical reduction of food (protein, carbohydrates, triglycerides) into soluble nutrients.
How is a bolus created?
Teeth masticate food and saliva provides lubrication and amylase to create a bolus.
How is chyme created?
Stomach movements and pepsin further digest food creating chyme.
What does the duodenum contain?
It is also called “brewer”.
-Contains brush boarder enzymes and receives additional digestive enzymes from pancreas
What disease might you have if you have a thinner mucus layer in your GI system?
Ulcers
Absorption:
Transport of nutrients across epithelium into blood or lymphatic system
Where are amino acids and monosaccharides absorbed?
In duodenum and jejunum through secondary active transport.
What do bile salts help with? Where are they from?
- Help facilitate absorption of lipids and fat soluble vitamins.
- From liver
Where are cobalamine (B12) and bile salts/acids absorbed?
Primarily in ileum.
What location absorbs water and electrolytes?
Small and large intestines
What is protein broken down into? What enzyme is involved?
Peptides, amino acids
-Proteases
What are carbohydrates broken down into? What enzyme is involved?
Monosaccharides
-Amylases, disaccharidases
What are lipids/triglycerides broken down into? What enzyme is involved?
Fatty acids, monoglycerides
-Lipases
Where are fatty acids, monoglycerides transported?
Into lymphatics
Where are peptides, amino acids, monosaccharides transported?
Into capillaries via secondary active transport.
Where is all blood leaving the small intestine directed?
Through the portal vein to the liver.
At “rest”, approximately ___ of blood flow goes to the gut which only accounts for ___ of body mass.
21%, 5%
Where does the liver receive 3/4 of its blood?
Portal vein
Where does the liver receive 1/4 of its blood?
Hepatic artery
Flow to the gut can increase. . .
4-5 fold during high gut activity
During exercise and emergency situations. . .
. . .massive vasoconstriction shunts blood away from gut
What increases blood flow in the small intestine?
Metabolic vasodilators (CO2, H+, K+, adenosine, etc.)
What can alter blood flow in the small intestine?
Autonomic and enteric neural influences can alter blood flow.
What is too big to get through capillary cells? What does this do to lipids?
Chylomicrons. So lipids are absorbed through lacteals which empty into the blood stream via the thoracic duct.
What are the causes of Mesenteric Ischemia?
- Occlusive mechanisms including thrombi (mesenteric infarction)
- Non-occlusive mechanisms including prolonged reflex vasoconstriction (due to hypovolemia, heart failure) or abnormal levels of circulating vasoconstrictors (e.g. EPI, angiotensin II)
What are the Effects of Mesenteric Ischemia?
- Postprandial Pain, Sitophobia (fear of eating)
- Necrosis of the tips of the villi
- Loss of barrier function of the wall of the gut and uptake of vasodilator toxins (endotoxin) from the gut resulting in Septic Shock
What is the purpose of Enterohepatic Circulation?
Recycling of bile salts/acids and some drugs?
Where are bile salts synthesized from?
Cholesterol in the liver
Where are bile salts stored?
In the gallbladder, before entering the duodenum
How are bile salts transported back into the liver?
Through the hepatic portal vein
What is the consequence of decreased bile flow to intestine?
Decreased absorption of fats and may cause steatorrhea (fatty stool).
What is the consequence of removal of the ileum?
Not enough absorption of fat –> steatorrhea?? (relisten)
Secretion:
Fluid into intestinal tract containing ions, digestive enzymes, mucins and bile
Fluid environment supports the uptake of. . .
. . .nutrients and minimizes damage to epithelium.
What supplies fluid to the GI tract?
Fluid supplied by organs that drain into the GI tract and GI epithelial cells.
Where are fluids reabsorbed?
In the small intestine with nutrients
What could cause decreased bile flow to intestine?
Stone blocking duct, any type of cholestasis
- Decreased flow can also cause accumulation of bilirubin
- Digestive enzymes may pool in pancreas —> pancreatitis
What nerves regulate fluid secretion in GI?
Parasympathetic, hormonal and enteric nerves
Where are digestive enzymes synthesized?
In specialized cells and packages into zymogen granules.
What does digestive enzymes secretion involve?
Usually involves a stimulus-induced increase in either cAMP or [Ca2+] (or both)… which then leads to zymogen granule docking and dumping.
What regulates transmural water movement?
Water moves across the epithelium drive by pressure created by osmotic gradients
How does water move tranmurally?
a) through the cells (transcellular route) with the help of water channels (aquaporins)
b) between cells (paracellular route) according to osmotic gradients driven by active electrolyte transport (also dependent on tightness of gap junctions)
What is “Conductivity” of the epithelium?
(leakiness) of the epithelia depends on the variable presence of absence of tight junctions.
What are causes of Diarrhea (increase in water in lumen)?
-“Osmotic diarrhea”
Small bowel overgrowth of bacteria leads to increased production of organic acids sufficient to pull water from the blood stream by osmosis.
-“Secretory diarrhea”
Infection leads to excess secretion of chloride drawing water into the lumen
What are the effects of Diarrhea?
- Dehydration and electrolyte balances
- Metabolic disturbance
What does Fluid flux depend on?
Surface area available for ion transport and residence time in the lumen.
How do some antidiarrheals work?
(Loperamide) - Work by slowing transit to increase fluid absorption.
What is the East-West Vector?
Influenced by surface area
What is the North-South Vector?
Influenced by motility –> transit time
What does motility control?
Length of time for digestion and absorption
What is the average transit time in the esophagus?
10 seconds
What is the average transit time in the stomach?
4-5 hours
What is the average transit time in the small intestine?
2.5-3 hours
What is the average transit time in the large intestine?
30-40 hours
What factors influence gastric motility?
- Variability between people (gender, anxiety)
- Contents of the meal (don’t necessarily leave stomach in the order they arrive)
Most of the GI tract is composed of. . .
Non-striated Smooth Muscle
What parts of the GI tract are not composed of non-striated smooth muscle?
There is STRIATED muscle in:
- Upper third of esophagus
- Pharynx
- External anal sphincter
What is the Non-striated Smooth Muscle of the GI tract like?
Spindle-shaped cells separated into branching bundles covered by connective tissue.
What are “gap junctions”?
Also called “nexuses”
-Low resistance electrical coupling between cells to enable the contraction wave to spread to adjacent cells
What modulates smooth muscle activity of the GI system?
NT released from intermittent swellings along the nerve axon
In what state is the lower esophageal sphincter usually?
Contracted
What are the Contractile Characteristics of GI Smooth Muscle?
- Rhythmic “phasic” (seconds) contractions and long “tonic” contractions (minutes to hours).
- Basal resting tension or “tone” is maintained without elevation in intracellular Ca2+ and without energy expenditure. (sphincters)
- GI smooth muscle has a remarkable ability to shorten (e.g., to 50% of resting length!!)
- Can initiate depolarization in response to stretch leading to contraction.
How do Sphincters work?
Proximal pressure leads to relaxation of sphincter. Distal pressure leads to contraction of sphincter.
What do Sphincters serve as?
One-way valves
-Most act autonomically
What is Excitation-Contraction Coupling?
Slow wave electrical activity (3-12 min, 5-15 mV) initiated by interstitial cells of Cajal are phasic and propagated over a few centimeters.
How are slow waves generated?
Due to increase in calcium followed by repolarization by K+ channels.
What can be altered by signals releasing calcium from internal stores or opening Ca2+ channels on plasma membranes of smooth muscle?
Amplitude, but not frequency of slow waves
What accompanies action potential?
Muscle contraction
What initiates Excitation-contraction coupling?
Increases in intracellular calcium ion concentration
What steps cause contraction?
- Binding of acetylcholine to muscarinic receptors.
- Increased influx of Ca2+ into the cell
- Activation of calmoduin-dependent myosin light chain kinase
- Phosphorylation of myosin
- Increased myosin ATPase activity and binding of myosin to actin.
What steps cause relaxation after contraction?
- Dephosphorylation of myosin by myosin light chain phosphatase.
- Relaxation, or sustained contraction due to the latch bridge and other mechanisms.
What are the main components of motility?
Contractions (Peristaltic & Segmenting)
What are Peristaltic Contractions?
Propel contents forward
What are Segmenting Contractions?
Contraction of circular muscles in that locally mix contents (churning), nonpropulsive
How do we know that it does not take 7 years to digest gum?
Migrating motor complex causes the stomach to completely empty every once in a while. This usually happens during fasting and the large opening between stomach and small intestine opens.
What is the Migrating Motor Complex?
Relaxation of sphincters and contractions in stomach and small intestine occurring during fasting (interdigestive) controlled by hormone motilin
What is the Enteric nervous system of the GI tract?
“Mini brain”
~100 million neurons
Where is the Submucosal Nerve Plexus of the Enteric nervous system?
It is within small and large intestine, sensory and blood flow, Meissner’s
Where is the Myenteric Nerve Plexus of the Enteric nervous system?
Between circular and longitudinal muscle layer from esophagus to internal anus Auerbach’s
How does the Enteric Nervous System operate?
Can operate autonomously to mediate short reflexes independent of input from the CNS
What detects changes in the GI tract?
They are often detected by intrinsic sensory receptors, including: stretch receptors, osmoreceptors, and chemoreceptors.
What does activation of receptors lead to?
It can lead to release of signaling molecules or upregulation of transporters.
Where are Chemosensitive taste receptors?
They localize to multiple spots in the body, but do not always evoke taste.
What excites afferent sensory neurons of the Enteric Nervous System?
Fast distention of the gut wall or chemical signals from the lumen of the gut transmitted to sensory neurons
What NT stimulates many of the sensory neurons of the gut?
Serotonin (5-HT)
What cells in the GI system secrete Serotonin?
Mucocal Enterochromaffin cells (ECL)
How do Afferent Sensory Neurons respond?
Respond with a few action potentials followed by hyper polarization (adaptation)
Where do Afferent sensory neurons transfer information about the gut environment?
They transfer information about gut environment to interneurons in myenteric plexus which relay signals up and down the gut.
Where are Efferent Motorneurons found?
Primarily in the myenteric plexus
What is the structure of Efferent Motorneurons?
Usually unipolar in struture
What excites Efferent Motorneurons?
Fast EPSPs
What doe Efferent Motorneurons respond with after being excited by an EPSP?
Sustained trains of action potentials.
What do Efferent Motorneurons carry?
“Efferent” information to GI smooth muscle, vascular smooth muscle, GI exocrine secretory cells and GI endocrine secretory cells
What do Excitatory fibers release?
ACh, Neurokinin A and Substance P
What do Inhibitory fibers release?
Vasoactive intestinal peptide (VIP) and nitric oxide (NO) on smooth muscle cells.
What do “Short” Neural Reflexes influencing GI function involve?
“Short” involve only nerves of the enteric plexes
What do “Long” Neural Reflexes influencing GI function involve?
“Long” involve both the CNS and ANS
What two systems do nutrients activate? What does this cause?
- Autonomic nervous system
- Enteric nervous system
- -> Promotes secretion and motility
Can the GI tract operate without input from higher centers?
Yes, but control of secretion and motility may be less than optimal
What are the two parts of the Extrinsic Autonomic Nervous System?
- Parasympathetic
- Sympathetic
What carries Afferent information leaving the GI tract?
Autonomic nerves
What are the Parasympathetic nerves of the Extrinsic autonomic nervous system?
Mostly cholinergic of vagus nerve; stimulates activity of the enteric plexuses, increases GI motility and secretory activity.
What are the Sympathetics nerves of the Extrinsic autonomic nervous system?
Mostly adrenergic, generally inhibits activity of the enteric plexuses, decreases GI motility, contracts GI sphincters, constricts GI microvasculature.
What molecules generate action potentials?
Acetylcholine, Parasympathetic stimulation, Cold, Stretch
What molecules DON’T generate action potentials?
Epinephrine, sympathetic stimulation
What can neural activity do to GI smooth muscle?
Increase or decrease contractile activity by influencing the amplitude (but not frequency) of the slow electric waves.
In general, what does parasympathetic activity do in GI muscle?
Increases activity, cholinergic, vagus “rest and digest”
In general, what does sympathetic activity do in GI muscle?
Decreases activity, noradrenaline, dopamine, neuropeptide Y
What is the Vago-vagal reflex?
Vagal afferent info is transmitted to autonomic centers in the medulla. Vagal effects coordinate excitatory and inhibitory activity within the Enteric Nervous System to mediate peristalsis.
What NT is excitatory and inhibitory in the Vago-Vagal reflex?
NO - Inhibitory
ACh - Excitatory
Acetylcholine:
Primary excitatory transmitter from sensory cells and from motoneurons to muscle, epithelium, secretory cells and at interneuronal junctions, Inc. intracellular Ca++
Gastrin releasing peptide:
Released from vagal nerve endings to stimulate G cell secretion of gastrin
Substance P:
(tachykinin) - an excitatory transmitter generally co-released with acetylcholine.
Vasoactive Intestinal Peptide (VIP):
Promotes motility
- Relaxes smooth muscle in esophagus and stomach
- Stimulate fluid secretion and promotes dilation of the GI vasculature. Inc. cAMP.
Nitric Oxide (NO):
An inhibitory transmitter co-release with VIP from inhibitory motoneurons, hydrophobic- intracellular targets
Gastrin:
G cells in antrum of stomach detect amino acids leading to pepsinogen and H+ release by parietal cells
Cholecystokinin (CCK):
I cells in D/J detect fat and amino acids, secretion of pancreatic enzymes and bile salts involved in fat uptake.
Secretin:
S cells primarily in D/J detect acid stimulates secretion of pancreatic juice including bicarbonate and inhibits gastric motility
GIP (Gastric Inhibitory Peptide or Glcuose-Dependent Insulinotropic Peptide (GIP)):
K cells in D/J detect carbohydrates and fat to inhibit gastric acid secretion and stimulate insulin release from pancreas.
Motilin:
Secreted by endocrine cells; released cyclically during fasting state to initiate Migrating Motor Complex
Portal blood concentration of what hormone will increase when the lumen of the small intestine is perfused with a buffered solution of pH 3?
Secretin
What are we mostly made up of?
Bacteria
10^12 cells in human body
What is the lumen of the gut equivalent to?
Being outside the body
What does bacteria create in the GI track?
Physiological inflammation
Where does bacteria reside in the GI track?
Outer mucus layer of the large intestine
How much of fecal mass is made up of bacteria?
60%
Changes in microbiota are associated with…
obesity and inflammatory diseases.
What do short-chain fatty acids produced by microbial fermentation of plant fibers do?
Improve glucose regulation
What is fiber converted to? What converts it?
Converted to short-chain fatty acids by bacteria in the colon.
Why is Butyrate important?
- Bacteria produces it from fiber
- Used by colonocytes for energy and has protective anti-inflammatory properties
What is Eructation?
Belching - Some air swallowed during eating is released
What does neutralization of gastric acid by bicarbonate generate?
CO2
What happens to gas byproducts of fermentation of fiber (anaerobes) in colon?
- Can be used by other bacteria
- Excreted by lungs
- Evaculated
What is Borborygmi?
Rumbling noise created by movement of gas in bowels
Why are some people’s flatulence flammable?
Only some people carry the methanobrevibacter smithii which produces the CH4 in the GI system. CH4 is flammable.
What can Delayed small intestine transit and diverticulum cause?
Small intestine bacterial overgrowth syndrome.
What does small intestine bacterial overgrowth syndrome involve?
- Gas and bloating from fermentation
- Compete for B12 uptake leading to anemia
- Deconjugate bile acids leading to steatorrhea
- Produce toxins altering epithelium
- Diagnose with hydrogen breath test (see increased levels of hydrogen)
What are properties of the GI tract that limit colonization by microorganisms?
- Saliva contains lactoferrin, lysozyme, and secretory IgA
- Acidic environment in stomach
- More lymphocytes in GI than the circulating immune system
- Mucus- mucins, IgA, lysozyme, lactoferrin
- Paneth cells secrete antimicrobial peptides (defensins)
- Peyer’s patches- ileum, contain M cells to transport antigens to B and T lymphocytes
- Digestive enzymes cleave bacteria
- Diarrhea
- Vomiting
- Microflora prevent colonization of pathogenic microorganisms (probiotics and probiotics,
What is the GI tract designed to do?
Mechanically and chemically digest carbohydrates, proteins and lipids into soluble nutrients
What is the purpose of segmenting contractions?
Facilitate mechanical digestions
What is the purpose of peristalsis?
Propels food forward
Where does most fluid and nutrient absorption occur?
Small Intestine
What aids in fluid and nutrient absorption?
The large surface area created by the villi
What controls GI motility and secretion?
Enteric nervous system (with input from CNS, GI hormones, and paracrine/immune regulators)
