GB 6. GIT Function I: Introduction and Gastric Function Flashcards
What regulates digestive function? [4]
[1] Intrinsic Nerve Plexuses (Enteric Nervous System, ENS)
[2] Extrinsic Nerves (Autonomic Nervous System, ANS)
[3] Autonomous Smooth Muscle Function
[4] Gastrointestinal Hormones
What are the 2 branches of the Extrinsic Nervous System of the gut?
[1] Sympathetic
- mainly inhibitory
[2] Parasympathetic
- mainly excitatory
What are the 3 main components of the intrinsic nerve plexus (enteric nervous system)? What are the functions of each?
[1] Sensory Neurons (intrinsic primary afferent)
- receives info from sensory receptors in mucosa + muscle
- info on gut contents + state of wall
- responds to stretch, tension, chemical nature of contents
[2] Motor Neurons (intrinsic primary efferent)
- controls GI motility + secretion
- activates intestinal functions (causes muscles to contract, vessels to dilate and electrolytes to be transported)
[3] Inter-Neurons
- integrates info from sensory neurons and provides it to enteric motor neurons
What are the 2 major networks of nerve fibres that are a part of the Enteric Nervous System? What are the functions of each?
[1] Submucosal (Meissner’s) Plexus
- intestinal secretions + local absorptive environment
[2] Myenteric (Auerbach’s) Plexus
- regulates intestinal smooth muscle
Does the extrinsic nervous system and intrinsic nervous system interact with one another?
- not entirely
- the enteric nervous system consists of cell bodies that receive inputs from the extrinsic nerves (sympathetic + parasympathetic)
The enteric nervous system is regulated by both excitatory and inhibitory nerves. Give some examples of both types.
Excitatory - ACh
Inhibitory - NO, VIP
Explain the extrinsic innervation (autonomic nervous system) of the gut. Some general functions, where they are located…
- not essential for motility
- nerves end mainly on plexus
- modify ongoing activity of ENS
- alters the level of hormone secretion
- can act directly on smooth muscle + glands
What does the parasympathetic nervous system (extrinsic innervation) effect GI activity?
- from VAGUS NERVE
- increases GI activity (gastrointestinal secretion, motor activity, sphincter and blood vessel contraction)
What does the sympathetic nervous system (extrinsic innervation) effect GI activity?
- from PREVERTEBRAL GANGLIA
- decreases GI activity (gastrointestinal secretion, motor activity, sphincter and blood vessel contraction)
What nerve does the parasympathetic nervous system come from?
VAGUS NERVE (+ pelvic nerves)
What nerve does the sympathetic nervous system come from?
PREVERTEBRAL GANGLIA
- coeliac, superior mesenteric + inferior mesenteric nerves
What is the main neurotransmitter of the parasympathetic nervous system? Describe the innervation of the upper and lower GIT
- ACh (excitatory!)
UPPER GIT:
- rich vagal innervation
- esophagus, stomach, small intestine + colon (up until splenic flexure)
LOWER GIT:
- rich pelvic innervation
- distal colon, rectum
Which innervation is more important in the GIT? Parasympathetic or sympathetic?
Parasympathetic is more important
What neurotransmitter is involved with the sympathetic nervous system in the GIT?
NA - inhibitory to GIT!
What are the interstitial cells of Cajal?
the pacemaker cells of the GIT
What is the location of the Interstitial Cells of Cajal, what do they do? How are they connected to smooth muscle?
- located in boundary of longitudinal and circular smooth muscle layers
- it leads to slow changes in resting membrane potential of GIT smooth muscle (cyclic slow wave activity)
- connected to smooth muscle by NEXI or GAP JUNCTIONS
What are slow waves? Describe how they work.
- they are spontaneous changes in resting membrane potential
- they bring the membrane closer or further from threshold potential
- amplitude of slow waves may reach a certain threshold in combo (through) mechanical, neural or hormonal factors
- when this happens, membrane Ca2+ channels are activated, resulting in calcium influx
- DEPOLARISATION RESULTS IN REPEATED RHYTHMICAL MUSCLE CONTRACTION
If the amplitude of the slow waves reach the threshold potential, what happens?
DEPOLARISATION OCCURS AND RESULTS IN REPEATED RHYTHMICAL MUSCLE CONTRACTION
What are slow waves not?
they are not action potentials!
What effect does the frequency of slow waves have on smooth muscle contraction?
as the frequency of slow waves increase, the frequency of smooth muscle contraction increases
- ultimately dependent on pacemaker cells
As the number of action potentials at the crest of the depolarisation phase increases, so does what?
- the strength of contraction increases
What are the 3 main enteric reflexes of the GIT? (just name them)
[1] Peristaltic Contraction (Peristalsis)
- slow waves of muscle contraction occur in the absence of the extrinsic nervous (vagal) influences
[2] Regulation of Gastric Emptying (Neural [Enterogastric] Reflex)
[3] Gastroileal Reflex (Hormonal)
Explain the enteric reflex - Neural (Enterogastric) Reflex.
- it is triggered by the presence of food in the duodenum (due to distension) [this is sensed by chemoreceptors + stretch receptors]
- results in inhibition of gastric motility and reduced rate of emptying of the stomach
ULTIMATELY - SLOWS DOWN ARRIVAL OF FOOD IN DUODENUM WHEN DUODENUM IS FULL
Explain the enteric reflex - Gastroileal Reflex (Hormonal).
- it is triggered by the presence of chyme in stomach (due to distension) and gastric peristalsis
- this leads to RELEASE OF GASTRIN
- contractions of the ileum + relaxation of the ileocaecal sphincter
- gastrin is a hormone that relaxes the sphincter
ALLOWS EMPTYING OF THE ILEAL CONTENTS INTO LARGE INTESTINE - PREPARES FOR INCOMING CHYME
What is the main function of the proximal stomach?
Storage - which is characterized by RELAXATION
What are the 3 ways that the proximal stomach relaxes?
[1] Receptive Relaxation
- food enters, muscles relax to accomodate
[2] Adaptive Relaxation (Reflex Relaxation)
- distension of stomach causes reflex relaxation
- involves nerve reflex (local + central)
- involves inhibitory neurotransmitter
- allows for prolonged storage for breakdown
[3] Feedback Relaxation
- signals triggered by nutrients in the duodenal lumen
- results in relaxation of gastric fundus
What is the main function of the distal stomach?
Mixing + Emptying
What is involved with mixing in the distal stomach?
[1] Spontaneous Electrical Activity
- Interstitial Cells of Cajal (gastric slow waves)
[2] Depolarizing Agents
- e.g. Vagus Nerve (ACh), Hormones (e.g. gastrin) and Stretch (distension + enteric reflex)
[3] Contractins
- they mix and propel food towards duodenum
- segmentation (local contractions causing constriction)
- propulsive movements
Explain the process of the emptying of the distal stomach.
- the narrow pyloric sphincter only allows a small amount of food to enter the duodenum with each contraction
- the basal electrical rhythm (BER) is initiated by pacemaker cells (of Cajal)
- vigorous peristalsis occurs near pylorus
- chyme either delivered to duodenum or forced back into stomach for further mixing
What are the 3 main MOTOR gastric functions?
[1] Proximal Stomach (Storage)
[2] Distal Stomach (Mixing)
[3] Distal Stomach (Emptying)
What cells (glands) are the gastric secretions secreted from?
Oxyntic Glands (proximal and part of distal stomach)
List the secretions that are secreted from the oxyntic glands. [5]
[1] Pepsinogen
- secreted from peptic (chief cells)
- protein digestion
[2] HCL (Intrinsic Factor)
- secreted from oxyntic (parietal) cells
- kills bacteria, low pH for pepsin
- vitamin B12 absorption
[3] Mucus + Bicarbonate
- secreted from mucous neck cells
- protects stomach epithelium from acid
[4] Histamine
- secreted from enterochromaffin-like cells (mast-like cells)
- stimulates gastric acid secretion (vasodilation, increased blood flow aids increased acid secretion)
[5] Somatostatin
- secreted from D-cells
- inhibits gastric acid secretion
Where is pepsinogen secreted from?
peptic (chief) cells
What is the function of pepsinogen?
protein digestion
Where is HCl (intrinsic factor) secreted from?
oxyntic (parietal) cells
What is the function of HCl?
- kills bacteria
- low pH for pepsin (to activate pepsinogen)
- vitamin B12 absorption
Where is mucus + bicarbonate secreted from?
mucous neck cells
What is the function of mucus and bicarbonate?
protects stomach epithelium from acid
Where is histamine secreted from?
enterochromaffin-like cells (mast-like cells)
What is the function of histamine?
- stimulates gastric acid secretion (vasodilation, increased blood flow aids increased acid secretion)
Where is somatostatin secreted from?
D-cells
What is the function of histamine?
inhibits gastric acid secretion
Where is mucous secreted from?
mucous cells
What is the function of mucous?
protects stomach epithelium from acid
Where is gastrin secreted from?
G cells (endocrine)
What is the function of gastrin?
- stimulates HCl secretion from oxyntic (parietal) cells
- stimulates pepsinogen secretion from peptic (chief) cells
List the secretions that are from the Pyloric Glands (antral region)? [3]
[1] Mucus
- secreted from mucous cells
- protects stomach epithelium from acid
[2] Gastrin
- secreted from G cells (endocrine)
- stimulates HCl secretion from oxyntic (parietal) cells and pepsinogen from peptic (chief) cells
[3] Somatostatin
- secreted from D cells
- inhibits gastric acid secretion
What do the surface epithelial cells secrete?
- secrete thick alkaline mucus containing mucin and bicarbonate
- functions to lubricate the stomach and protect the mucosa from acid and pepsin
What is the function of the thick alkaline mucus containing mucin and bicarbonate?
functions to lubricate the stomach and protect the mucosa from acid and pepsi
What are the 3 major cells in which gastric secretions are secreted from?
[1] Oxyntic Glands
[2] Pyloric Glands
[3] Surface Epithelial Cells
How is pepsinogen converted to pepsin?
HCl cleaves a small fragment off of pepsinogen molecules to create active pepsin
- pepsin can then activate other pepsinogen molecules by cleaving off amino acids to form pepsin
Is pepsinogen the active or inactive form?
inactive form
- it gets changed into pepsin
What are the mediators of acid secretion? What increases gastric acid secretion and what decreases gastric acid secretion?
INCREASES SECRETION:
[1] ACh
[2] Gastrin
[3] Histamine
DECREASES SECRETION:
[1] Prostaglandins
[2] Somatostatin
What receptors are involved with the acid secretion mediator, ACh?
M3 receptors
What receptors are involved with the acid secretion mediator, Gastrin?
CCK-2 receptors
What receptors are involved with the acid secretion mediator, Histamine?
SSTR2 receptors
What is the function of the proton pump (H+/K+ ATPase) - the oxyntic cell?
- driving force is the H+/K+ ATPase
- – pumps H+ out in exchange for K+
- Cl- enters the cell in exchange for HCO3- and leaves for lumen through CL- channels down electrochemical gradient
What is the final item that all the gastric secretion mediators finally have an effect on?
they have an effect on the H+/K+ ATPase pump (proton pump)
Does the stomach have a large or small surface area for absorption? Describe what the stomach absorbs (its aborptive abilities).
stomach has SMALL surface area for absorption
- it lacks villus of small intestine
- it has tight junctions between epithelial cells
- absorbs VERY FEW substances
- absorbs SMALL amounts of certain LIPID-SOLUBLE compounds
- only HIGHLY LIPID SOLUBLE agents absorbed to significant extent
- – e.g. alcohol, weak acids, non-steroidal anti-inflammatory
What are some of the highly lipid-soluble agents taht the stomach can absorb to a significant extent?
[1] Alcohol
- lipid soluble
[2] Weak Acids
- e.g. aspirin
- largely uncharged at pH of stomach, passes through the lining quickly
[3] Non-Steroidal Anti-Inflammatory Drugs
- e.g ibuprofen
What are the 2 components of the gastrointestinal barrier? What are they made up of?
[1] Intrinsic Barrier
- epithelial cell lining
- tight junctions that tie them together
[2] Extrinsic Barrier
- consists of secretions and other influences which affect epithelial cells and maintain barrier function
- – mucous + bicarbonate secretion
- – hormones and cytokines (affects rates of cell proliferation)
- – prostaglandins (e.g. prostaglandin E2 - PGE2)
What can lead to damage/alteration inthe mucosal defence of the stomach? [4] (just list them)
[1] Gastric Acid (Pepsin)
[2] H. Pylori
[3] Drugs (NSAIDs, aspirin, alcohol)
[4] Stress
What are some of the causes of Gastritis and Peptic Ulcer Disease?
[1] Excess Acid (Pepsin)
- due to reflux, diet, stress, caffeine, smoking…
[2] Decreased Mucus
- irritants to mucosal barrier
[3] Drug Adverse Effects
- aspirin // NSAIDs
- weak acids become concentrated into mucosal cells (they can cross the barrier and then build up)
- inhbition of COX-1 and COX-2 enzymes are important for the maintenance of the integrity of the gastric epithelium + mucus barrier
Why are the COX-1 and COX-2 enzymes important for the maintenance of the gastric epithelium and mucus barrier?
- prostaglandins (esp. PGE2) have protective role physiologically
- they inhibit acid secretion and stimulate mucus secretion
- they inhibit acid secretion + stimulate mucus secretion
- reduction in mucosal defence and blood flow will cause gastric ulceration (leading to inhibition of prostaglandin synthesis)
- neutrophil-endothelial interaction occur as a result of the vascular disturbances and neutrophil activation
- they mediate the adherence of leukocytes to mucosal endothelial cells
What are the 2 main insults that NSAIDs may have?
[1] Primary Insult
- topical irritation
- leads to direct epithelial acid damage
[2] Secondary Insult
- due to COX-1 and COX-2 inhibition
- leads to prostaglanding inhibition, reduced blood flow, leukocyte adherence
What does Helicobacter pylori do? What can it lead to?
- helicobacter pylori is a bacterium that causes peptic ulcer disease
- it infects the antrum of stomach
- it causes infiltration of leukocytes (inflammation of gastric mucosa)
- mainly all duodenal + gastric ulcers have H. pylori infection
What is the treatment for an ulcer due to H.pylori bacteria?
Triple Therapy (first-line therapy, 2 antibiotics and a proton pump inhibitor)
What is the Zollinger-Ellison Syndrome? Why does it occur? What does it lead to?
- RARE cause of recurrent peptic ulceration associated with increased gastrin blood concentrations
- excess acid secretion due to a primary non-beta cell gastrin-secreting tumour in pancreas
- leads to increased mass of parietal and enterochromaffin-like cells suceptible to overstimulation by gastrin
What is the treatment for Zollinger-Ellison syndrome?
therapy directed at controlling the gastric acid hypersecretion and removal of the gastrinoma
