GI I & II

Question 1

What are the four major physiological processes that the GI tract participates in (in order to perform its main functions)?

Describe them.

Answer 1

motility- seq. of contraction of layers in SMC, req to reduce size of food particles allowing an increased surface area for chemical digestion by enzymes, req for mixing food particles w enzymes in the GI lumen and to propel ingested food from mouth toward rectum

secretion- release of enzymes, biological detergents, mucus, ions and water in GI lumen by GI epithelia and associated glands (salivary, pancreas, liver, gall bladder)

digestion-macromolecules converted to smaller, absorb-able molecules. (physical and chemical modification- of carbohydrates, aa, lipids)

absorption- nutrients, electrolytes and water absorbed from GI lumen into bloodstream

(GI tract also participates in excretion of waste substances)

Question 2

Describe the excretion role of the GI tract.

Answer 2

GI tract stores and excretes waste substances from ingested food materials. It also excretes products from the liver such as cholesterol, steroids, and drug metabolites

Question 3

Describe why the immunological function of the GI tract is important.

Answer 3

GI tract is open to external environment - so its vulnerable to infectious microorganisms that can enter along w food and water… to protect, it possesses complex defense system of immune cells and other non-specific defense mechanisms

largest immune organ in body

Question 4

Describe the major functional segments (anatomy) of the GI tract.

Answer 4

Slide 12

mouth and pharynx
esophagus
stomach
small intestine (duodenum, jejunum, ileum)
large intestine (colons)
rectum
anus

Question 5

What are the associated GI glandular organs?

Answer 5

salivary
pancreas
liver 
gall bladder
endocrine glands or cells

Question 6

What are sphincters? What are the major ones in GI tract?

Answer 6

sphincters are specialized circular muscle structures (smooth or skeletal) controlling the flow of GI contents between distinct structures

They include:

• upper esophageal (between pharynx and esophagus) (UES)
• lower esophageal (between esophagus and stomach) (LES)
• pyloric (between stomach and duodenum)
• sphincter of Oddi
• ileocecal (between ilium and cecum)
• internal and external anal

Question 7

What is the role of the UES?

Answer 7

imp. for regulating both reflux of food when food enters and to keep it from getting back into airway so protects airway and helps when we swallow food so doesn’t go into airway

Question 8

Why is LES important? What happens if it becomes leaky?

Answer 8

between esophagus and stomach, imp. to regulate, opens so food can enter into stomach then immed. closes down, imp. for regulating gastric reflux.

when food enters stomach its mixed with all the gastric secretion (acid, pepsin and corrosive things) ok for that in stomach, stomach has well built def. mechanism so acid cannot destroy stomach mucosa but if that stuff in duodenum then there will be some problems -duodenum has own def by secreting bicarb and neutralizing it, if in esophagus then also big problem bc we don’t have anything to neutralize it. so the LES is def mech. if LES becomes leaky then gastric contents can reflux back into esophagus (esophageal reflux disease)

Question 9

What is the purpose of the ileocecal sphincter?

Answer 9

guards between ilium and cecum (last segment of small intestine - guards from any material from colon to small intestine)

Question 10

Describe the splanchnic circulation. What are three striking features?

Answer 10

large blood flow (receives 25% of cardiac output)

large reservoir function

the diversity of organs that it perfuses

Question 11

Describe the three major arteries supplying the abdominal organs (and what they perfuse).

Answer 11

Celiac artery: supplies the liver, spleen and stomach.

Superior mesenteric artery: supplies the pancreas, small intestine, and proximal colon.

Inferior mesenteric artery: supplies the distal colon

Slide 14

Question 12

Describe the portal circulation. How is it different than other organ systems?

Why is this important?

Answer 12

Unlike other organ systems, the venous drainage from the GI tract does not return directly to the heart.

The venous blood arising from the abdominal organs flows to the liver first via portal vein (portal circulation).

Blood from the liver is transported via hepatic veins to the inferior vena cava.

liver has detoxification function, really is another defense mechanism the body has, any kind of toxin or bacteria..if something escaped and being absorbed in blood, don’t want to let it go into circulation directly. another step of defense-why all portal blood circulated through liver and enter through hepatic veins, vena cava, to heart

Question 13

Describe lymphatic drainage. What is it important for?

Answer 13

This is important for the transport of lipids and lipid-soluble molecules (including some vitamins and drugs).

These molecules are too large to enter capillaries and pass into lymph vessels.

They are then drained via the thoracic duct into systemic circulation.

Question 14

What are the layers that make up the gut wall?

Answer 14

mucosa (innermost)
submucosa
muscularis externa
serosa (outermost)

Slide 16

Question 15

What makes up the innermost layer?

Answer 15

innermost layer is mucosa and made up of

epithelium
lamina propria
muscularis mucosae

slide 17, 18, 19

Question 16

Describe the epithelium.
What layer is it part of?

Describe its cells. Which is most abundant (absorptive enterocytes or enteroendocrine cells?)

What are the other specialized cells and what do they do?

Answer 16

Part of mucosa.
-is a single continuous layer of specialized cells lining the lumen of entire GI tract and interconnected via tight junctions.

Absorptive enterocytes - most abundant - plays vital role in digestion, absorption.

Enteroendocrine cells - releases regulatory peptides, amines - regulate GI function.

Other specialized cells are:
Gastric mucosal cells - produce protons.
Mucin-producing cells all throughout - produce mucin (glycoprotein).

Question 17

Describe the nature of the esophageal and intestinal epithelium.

Answer 17

Esophageal epithelium - helps in transportation of swallowed food (no absorption) - squamous type.

Intestinal epithelium - helps in absorption or selective uptake of nutrients, ions, water – columnar type.

Question 18

Describe the surface area of small intestine epithelium.

Describe the epithelial lining of the GI tract.

Answer 18

The surface area of small intestinal epithelium consists of: villi and crypts.

The epithelial lining of the GI tract is continuously renewed. The cells at the villus tip are eventually shed via cell death - lifespan about 3-5 days.

(dont want them to maintain so long bc can develop mutations…) programmed cell death by which tips get rid of these epithelial cells.

Question 19

Where are the proliferative cells localized?

Answer 19

crypts - zone of intestinal stem cells

Question 20

Compare villi to crypts. (structurally)

Answer 20

Villi are finger-like projections (units of absorption) and crypts are invaginations or folds.

The villus is called the unit of absorption.

Question 21

Describe villi. How do they affect surface area? What would happen if there was reduced surface area? Give a clinical example.

Answer 21

The villus is called the unit of absorption.

Epithelial cell on the surface of a villus (enterocytes on luminal side of cells) have numerous cytoplasmic extensions at the luminal surface – microvilli or brush border.

The mucosal folds, villi, and microvilli increase the surface area of the small intestine ~ 600 fold.

Reduced surface area - malabsorption; Example: Celiac Disease - flattened villi > reduced surface area > malabsorption of nutrients > malnutrition.

Question 22

Describe the composition of apical microvillar membrane.

Answer 22

high % of cholesterol and sphingolipids (raft formation)

Question 23

Describe lamina propria.

Answer 23

Layer of mucosa -Immediately below the epithelium.

• Consists of connective tissue - collagen and elastin fibrils.
• Rich in glands, contains lymph vessels and nodes, capillaries, nerve fibers.

Question 24

Describe muscularis mucosae.

Answer 24

Layer of mucosa.

Thin layer of smooth muscle cells in a folding configuration caused by contractions.

Question 25

Describe submucosa.
What does it consist of?

What does it help integrate?

Answer 25

The layer after mucosa, consists of connective tissue - collagen and elastin fibrils.

Glands are present in some regions.

Large nerve trunks and large blood and lymph vessels are present.

This consists of a dense network of nerve cells called the submucosal plexus of the enteric nervous system (also called Meissner’s plexus- Part of “The Little Brain in the Gut).

Helps in the integration of motor and secretory activities.

Question 26

Describe the muscularis externa or muscularis propria.

Describe the 2 layers of SMC. What is between them?

Answer 26

Contractions of this layer helps in mixing and propelling contents of the GI tract.

Consists of 2 layers of smooth muscle cells:
Inner circular muscle layer
Outer longitudinal muscle layer

Between these 2 layers lies the myenteric plexus (Auerbach’s plexus, the other part of “The Little Brain in the Gut”).

Question 27

Describe serosa.

Answer 27

This is the outermost layer of the GI tract.

Consists of a layer of squamous mesothelial cells.

It is part of the mesentery that lines the surface of the abdominal wall and keep the organs suspended in the cavity.

Secretion is viscous, lubricates the abdominal organs to reduce friction between the abdominal organs during contraction/relaxation of GI tract.

Question 28

Describe the regulation of the GI tract:

It undergoes various periods. Describe.

What are the three principle regulatory mechanisms involved in intercommunication between the distal segments of the long digestive tube?

Answer 28

GI tract undergoes periods of relative quiescence (intermeal period) or intense activity after food intake (postprandial period).

Varies with the meal composition;

Being a long digestive tube there is intercommunication between its distant segments;

Three principle regulatory mechanisms are involved:
Endocrine
Paracrine
Neural

Question 29

Describe endocrine regulation of GI tract. What are sensor cells called?

How do they respond to a stimulus?

Answer 29

Sensor cells of the GI system are called enteroendocrine cells (EECs).

They respond to a stimulus by secreting a regulatory peptide or hormone, which travels via circulation to a target cell at distant location.

Question 30

Describe open and closed EECs.

Answer 30

A typical EEC is “open” type- meaning the apex of cell is in contact with the GI lumen (for sensing) and its base releases the hormone that diffuses into local capillaries.

There are also “closed” types- these do not have contact with the GI luminal surface (example ECL cells of gastric epithelium).

Question 31

Describe how EEC hormones or peptides trigger a signal transduction cascade.

Where might target cells be? Describe them?

Describe Gastrin.

Answer 31

The target cells express specific receptors for the GI hormone.

EEC hormones or peptides (released from the basolateral membrane) bind to a membrane receptor in a target cell and trigger a signal transduction cascade.

The target cells can be located in other parts of the GI tract or in the associated glandular structures (example, pancreas).

Target cells can also be in other tissues outside of GI that are not directly connected with GI regulation.

Some EEC can be directly stimulated by neuronal input not associated with a meal.

Example: Gastrin (hormone) is released by G cells in the distal part of stomach – stimulates acid secretion by the ECL and parietal cells (gastric corpus or body).

Question 32

Describe paracrine regulation. What are target cells?

Answer 32

Where a chemical messenger or regulatory peptide released from a sensing cell (often EECs) - acts on a nearby target cell by diffusion through the interstitial space (not transported via circulation).

Target cells: smooth muscle, absorptive enterocytes, secretory cells in glands and other EECs.

Question 33

Describe histamine.

Answer 33

Histamine released by enterochromaffin-like cells (ECL) in the stomach diffuses through the interstitial space and binds to neighboring parietal cells that then secrete HCl.

paracrine

Question 34

Describe serotonin.

Answer 34

Serotonin (5-hydroxytryptamine or 5-HT) released from enteric neurons, mucosal mast cells and specialized EECs called enterochromaffin cells regulate the contractile activity of smooth muscle cells in the GI system.

Question 35

Describe cholecystokinin.

Answer 35

Cholecystokinin can be both paracrine and endocrine regulator- it is released from the duodenum in response to dietary protein, lipid- acts locally on nerve terminals (paracrine effect) and on pancreas (endocrine effect).

Question 36

Describe the immune system in the Gi tract. What do they defend against? What do these cells release?

Answer 36

Half of the mass of the immune system in the human body is present in the GI tract.

Immune cells in the GI system defend the body from bacteria, antigens etc.

These cells also release paracrine factors.

There are serious diseases of the GI immune system linked to its hyperactivity.

Question 37

Describe celiac disease.

Answer 37

(gluten enteropathy)
Effects approx. 2 million
people in North America.

This is due to an allergic response to a component in gluten of wheat flour, rye and barley - gliadin.

This causes an inflammatory reaction in the small intestine.
This results in reduction of density and length of microvilli.

Causes reduced absorption of nutrients.

The only known effective treatment is gluten-free diet.

See slide 36 diagram.

Question 38

Describe the secretion site, stimuli for secretion and action of Gastrin.
Endocrine, paracrine or both?

Answer 38

(endocrine)

secretion site: gastric antrum (G cells)

Stimuli for secretion: small peptides and aminoacids

action:
- increases parietal cells- H+ secretion
- increases ECL cells-histamine secretion
- increases growth of gastric mucosa

Question 39

Describe the secretion site, stimuli for secretion and action of CCK (choleystokinin)
Endocrine, paracrine or both?

Answer 39

(Paracrine and endocrine)

secretion site: “I” cells of duodenum

Stimuli for secretion: fatty acids, hydrolyzed proteins

action: 
decreases gastric emptying and H+ secretion
-decreases food intake
-increases pancreatic enzyme secretion
-increases contraction of gallbladder

Question 40

Describe the secretion site, stimuli for secretion and action of secretin.
Endocrine, paracrine or both?

Answer 40

(paracrine and endocrine)

secretion site: “S cells” of the duodenum

Stimuli for secretion: H+ protons in duodenum

action:
increase pancreatic ductal secretion (H2O and HCO3-)

Question 41

Describe the secretion site, stimuli for secretion and action of GIP (glucoinsulintropic peptide)
Endocrine, paracrine or both?

Answer 41

(endocrine)

secretion site: ‘K’ cells of duodenum and jejunum

Stimuli for secretion: fatty acids and glucose

action: increase insulin secretion from pancreas (Beta cells)

Question 42

Describe the secretion site, stimuli for secretion and action of Peptide YY (PYY)
Endocrine, paracrine or both?

Answer 42

paracrine and endocrine

secretion site: ‘L’ cells of intestine

Stimuli for secretion: fatty acids, glucose, hydrolyzed protein

action:
- decrease gastric emptying and acid secretion
- decrease pancreatic secretion
- decrease intestinal motility
- decrease food intake

Question 43

Describe the secretion site, stimuli for secretion and action of proglucagon derived peptides (GLP-1/2)
Endocrine, paracrine or both?

Answer 43

(paracrine and endocrine)

secretion site: ‘L’ cells of intestine

Stimuli for secretion: fatty acids, glucose, hydrolyzed protein

action: glucose homeostasis; increase epithelial cell proliferation

Question 44

When does neural regulation occur?

Describe the 2 sets of nerves that innervate the gut.

Answer 44

Neural regulation occurs when a neurotransmitter is released from a nerve terminal in the GI tract

This neurotransmitter then effects the cell that is innervated.

Neural regulation is very important both within an organ and between distant parts of the GI tract.

The gut is innervated by 2 sets of nerves:

Extrinsic and intrinsic nervous systems.

Question 45

Describe the extrinsic and intrinsic nervous systems. What is the difference?

Answer 45

Extrinsic nervous system:

nerves that innervate the gut, with cell bodies located outside the gut wall.
These extrinsic nerves are part of autonomic nervous system (ANS).

Intrinsic or enteric nervous system (ENS):

has cell bodies that are contained within the wall of the gut
submucosal plexus
myenteric plexus

Some GI functions are highly dependent on extrinsic nervous system
yet others are independent and mediated entirely by ENS.

Question 46

Describe the extrinsic neural innervation in more detail.

Describe its parasympathetic innervation - What are the two main nerves and what do they innervate?

Answer 46

Extrinsic neural innervation - via two major subdivisions of ANS:
Parasympathetic
Sympathetic

Parasympathetic Innervation
Via vagal and pelvic nerves

The vagal nerve innervates the:
esophagus, stomach, gallbladder, pancreas, 1st part of the intestine, cecum, proximal part of colon.

The pelvic nerves innervate the:
the distal part of the colon and anorectal region.

Slide 41, 42

Question 47

Where do preganglionic parasympathetic nerve cell bodies originate for both vagus and pelvic nerves?

Where do preganglionic fibers synapse? (long or short?)

Where is info relayed?

Describe post-ganglionic neurons. What types, what do they release?

Answer 47

In general activates GI function.

Preganglionic nerve cell bodies -brain stem (vagus), sacral spinal cord (pelvic).

Long preganglionic fibers synapse in ganglia in the walls of the organs within ENS.

Information is then relayed to the smooth muscle, endocrine and secretory cells.

Post-ganglionic neurons are either cholinergic or peptidergic.

Cholinergic neurons release acetylcholine (nicotinic synapse).

Peptidergic neurons release various peptides – substance P, vasoactive intestinal peptide (VIP).

Question 48

Within the vagus nerve, what percent are afferent vs efferent fibers?

What do afferent fibers deliver?

What are vagovagal reflexes?

Answer 48

Vagus nerve is mixed – 75% are afferent and 25% are efferent fibers.

The afferent fibers deliver sensory information from the periphery (e.g. from mechanoreceptors and chemoreceptors of gut wall) to central nervous system (CNS).

The vagal afferents send sensory information to the CNS, where they synapse with an interneuron, which then drives activity in the efferent motor neuron.

Vagovagal reflexes – both efferent and afferent in the vagus nerve.

Question 49

Describe sympathetic innervation:

What effect does it generally have on GI function (what is the exception)?

Describe preganglionic fibers - where do they synapse? Long/short?

What are the sympathetic ganglia that serve the GI tract?

What type are sympathetic postganglionic fibers? What do they release?

Answer 49

In general inhibits GI function (inhibits smooth muscle function.

Exception: GI Sphincter muscles are activated by sympathetic innervation;

Preganglionic fibers here are shorter and synapse in ganglia outside the GI tract.

The sympathetic ganglia that serve the GI tract – celiac, superior mesenteric and inferior mesenteric.

Post ganglionic fibers are adrenergic – i.e. release norepinephrine.

Question 50

What do post-ganglionic fibers synapse on?

What percent of symp. nerve fibers are afferent/efferent?

Answer 50

Post ganglionic fibers leave the sympathetic ganglia – synapse on ganglia in ENS or directly innervate smooth muscle, endocrine or secretory cells.

About 50% of the sympathetic nerve fibers are afferent and 50% efferent.

Thus sensory and motor information is relayed back and forth between GI tract and CNS, coordinated by the submucosal and myenteric plexuses.

Question 51

Draw a summary of extrinsic NS for para/symp and which layers they synapse on.

Answer 51

Slide 48.

Slide 49.

Question 52

What are the two major plexuses of the Enteric NS?

Where is each one?

How are neurons in the 2 plexuses linked?

Why is the ENS referred to as “little brain of the gut”?

Answer 52

Enteric Nervous System (ENS) has two major plexuses:
Myenteric plexus
Submucosal plexus

The myenteric plexus - between the longitudinal and circular muscle layers.

The submucosal plexus - in the submucosa.

Neurons in the two plexuses are linked by interganglionic strands.

Neurons are afferent, interneurons or efferent. Thus ENS can act autonomously from extrinsic innervation – also called “little brain in the gut”.
However, these neurons receive input from extrinsic (parasympathetic and sympathetic) neurons which modulate their activity.

Many neurochemicals or neurocrines are released by the neurons of ENS:

• Neurotransmitters
• Neuromodulators (modulate the activity of neurotransmitters).

Slide 52.

Question 53

Describe the brain-gut axis/neural control of GI system starting with stimuli.

Answer 53

Slide 53.

stimuli that act on sensors (mechanical and chemical) which then trigger brain and spinal cord and ENS. (brain and spinal cord also stimulates ENS)

ENS stimulates effectors (motility and secretion and blood flow)

Question 54

Describe the following neuromodulators providing their source and actions:

acetylcholine (Ach)
Norepinephrine (NE)
Vasoactive Intestinal peptide (VIP)

Answer 54

Ach (from cholinergic neurons)
-contraction of SMC in wall; relaxation of sphincters
increases salivary, gastric, and pancreatic secretions

NE (from adernergic neurons)
-relaxation of SMC in wall; contraction of sphincters
increases salivary secretion

VIP (from neurons of mucosa and smooth muscle)
relaxation of smooth muscle;
increase intestinal and pancreatic secretion

Question 55

Describe the following neuromodulators providing their source and actions:

Gastrin-releasing peptide (GRP) or Bombesin

Enkephalins (opiates)

Neuropeptide Y

Substance P

Answer 55

GRP/Bombesin (from neurons of gastric mucosa) increase gastric secretion

Enkephalins (opiates) from neurons of muscosa and smooth muscle

• contraction of smooth muscles
• decrease intestinal secretion

Neuropeptide Y (neurons of mucosa and smooth muscle)
relaxation of smooth muscle;
decrease intestinal secretion

Substance P (co-secreted with Ach) -
contraction of smooth muscle;
increase salivary secretion

Question 56

What is GI motility?

What are almost all contractile tissues of GI tract made of/what type of cells?
(Where is this not the case?/What type of cells are there?)

Describe the connections between cells in GI tract, what is the purpose of this type of connection?

Answer 56

Is the contraction and relaxation of the walls and sphincters of GI tract.

Almost all contractile tissues of GI tract are smooth muscles.

Those in pharynx, the upper 1/3rd of esophagus, the external anal sphincter are striated muscle.

Smooth muscle of GI tract forms gap junctions (low resistance) with interstitial cells of Cajal (ICCs) – permits rapid cell-to-cell spread of action potentials.

Question 57

Describe the two types of GI smooth muscle contraction.

Answer 57

Phasic contractions – periodic contractions followed by relaxation – found in esophagus, gastric antrum, small intestine – involved in mixing and propulsion.

Tonic contractions – a constant level of contraction or tone without regular periods of relaxation – found in orad (upper) region of stomach and lower esophagheal, ileocecal and internal anal sphincters.

Question 58

What are slow waves?

When might an AP occur?

Answer 58

Slow Waves are a unique feature of GI smooth muscle electrical activity.

They are slow electrical waves – (oscillating depolarization and repolarization of the membrane potential) - that are not large enough to elicit action potential and/or contractions

If at the plateau or peak of the slow wave, the membrane potential is depolarized up to the threshold, then action potential occurs “on top of” the slow wave.

Question 59

What follows the AP?

How do wave frequencies vary in stomach vs duodenum?

Where do slow waves originate?

Answer 59

Contraction or tension follows the action potential.

Wave frequency varies in distinct regions of GI tract (3/min in stomach, 12/min in duodenum).

The slow waves originate in the interstitial cells of Cajal (ICCs), located between the longitudinal and circular layers of muscularis externa – they are called the pacemaker cells for GI smooth muscle.

slow waves v slow in stomach, in duodenum they are stronger, much more frequent

Question 60

What happens in smooth muscle when there are no action potentials?

What happens when AP occur on top of slow waves? What follows?

How do individual AP in smooth muscle differ from skeletal muscles?

What controls amplitude and frequency of slow waves?

Answer 60

Even sub-threshold slow waves produce weak contraction; so even without action potentials, the smooth muscle exhibits basal, tonic contractions.

When action potentials occur on top of the slow waves, it is followed by much stronger contractions or phasic contractions.

Contrary to the skeletal muscles, individual action potentials in the smooth muscle are not followed by separate twitches - they summate into one long contraction.

The amplitude and to a lesser extent the frequency of slow wave are under neural, hormonal and paracrine influences.

Question 61

Where do segmentation contractions usually occur?

What do they allow?

A small section contracts, then what happens? What results?

Answer 61

Segmentation contractions occur predominantly in the small and large intestine.

These allow mixing of the luminal contents with GI tract secretions and increase exposure to the mucosal surfaces where absorption occurs.

A small section contracts, splitting the chyme, sending it in both orad and caudad directions.

This section then relaxes allowing chyme to merge – this serves to mix chyme but produces no forward movement.

Question 62

Where do peristaltic contractions occur?

What purpose do they serve?

What happens orad and caudad to the bolus? What is the result/which direction will it go?

What nt are involved in orad contraction? Which are involved in caudad relaxation?

Answer 62

Peristaltic contractions occur in the pharynx, esophagus, gastric antrum, small and large intestine.

These contractions help to propel the chyme along the GI tract.

Here a contraction occurs at a point orad to the bolus, simultaneously, the portion caudad to the bolus relaxes; the chyme is thus propelled in the caudad direction.

Neurotransmitters:
Ach and substance P are involved in orad contraction
VIP and nitric oxide are involved in caudad relaxation.