Large Intestines, Constipation, Diarrhoea and Lactose intolerance Flashcards
What type of muscle aids GI motility?
Smooth Muscle
Where in the body is skeletal muscle the most important?
mouth, pharynx, upper oesophagus, external anal sphincter
What happens to the lumen of the large intestines when circular muscles contract?
it becomes narrower and longer
What happens to the intestine when longitudinal muscles contract?
It becomes shorter and fatter
What happens to the mucosa when the muscularis mucosae contracts?
There is a change in the absorptive and secretory area
Where are the neurones of the enteric nervous system located?
In the ganglia within the myenteric and submucous plexus solely in the GI tissue (making it intrinsic)
What is used to connect the myenteric and submucous plexus?
Integanglionic fibre tracts
What is a pro of the GI tissue having an intrinsic nervous system?
it forms a complete reflex circuit that can operate independently to the rest of the nervous system, but is strongly modulated by hormones and extrinsic nerve input.
What is the enteric nervous system comprised of?
Sensory neurones, interneurones, effector neurones
Examples of sensory neurones?
mechanoreceptors, chemoreceptors, thermoreceptors
What are effector neurones?
excitatory and inhibitory motor neurones which supply the longitudinal and circular smooth muscles, secretory epithelium, endocrine cells and blood vessels.
How does the parasympathetic system work?
the preganglionic fibres send ACh across the synapse to the post ganglionic neurones within the enteric nervous system (ENS) and have a excitatory and inhibitory influence.
Excitatory influence of the parasympathetic system in the ENS in the GI?
1) increased gastric, pancreatic and small intestinal secretion, blood flow and smooth muscle contraction
Inhibitory influence of the parasympathetic system in the ENS in the GI?
1) relaxation of some sphincters, receptive relaxation of stomach
How does the sympathetic system work?
The preganglionic fibres release ACh across the synapse to the postganglionic fibres. These then release NA (noradrenaline) supplying mainly the enteric neurones but also other structures. This all occursr in the prevertebral ganglia.
Three prevertebral ganglia supplied to the GI?
1) celiac
2) superior mesenteric
3) inferior mesenteric
Which of the two is more fuctionally important, the sympathetic or the parasympathetic system?
the parasympathetic system
What is the inhibitory influence of the sympathetic system in the ENS on the GI?
it decreases the motility, secretion and blood flow.
Smooth muscle cells of the GI tract are coupled by what and what is the effect of this coupling?
coupled by gap junctions and allows the spread of electrical currents from cell to cell forming a functional syncytium.
What is a functional syncytium?
When hundreds of cells are depolarized and contract at the same time
What is the spontaneous activity of the smooth muscle in the GI tract modulated by?
1) intrinsic (enteric) and extrinsic (autonomic) nerves
2) hormones
What are slow waves?
They’re rhythmic patterns of membrane depolarization and repolarization that spread from cell to cell via gap junctions. They occur in the stomach, SI and LI
What drives slow waves?
Interstitial Cells of Cajal (ICCs)
What do ICCs do?
they’re the pacemaker cells in the stomach, SI and LI stimulating spontaneous electrical activity
What causes contraction of smooth muscle?
if the slow wave amplitude is big enough to trigger action potentials. The contraction force is related to the number of action potentials discharged
What mediates the slow wave?
voltage-activated Ca2+ channel
Where are ICCs located?
between longitudinal and circular muscle layers and in the submucosa. They form gap junctions with each other and smooth muscle.
What do slow waves determine?
The Basic Electrical Rhythm (BER) - not all slow waves trigger contraction
three factors that affect if the slow wave amplitude reaches threshold?
1) neuronal stimuli
2) hormonal stimuli
3) mechanical stimuli
What happens to the BER along the GI tract?
it varies along the length of the G.I. tract
What is the BER in the stomach?
3 slow waves per minute
What is the BER in the duodenum?
1-12 waves per minute
What is the BER in the terminal ileum?
8 waves per minute. It’s used to drive luminal contents in the aboral directon
What is aboral?
side or end that is furthest from the mouth
What is the BER in the proximal colon?
8 waves per minute
What is the BER in the distal colon?
16 waves per minute for the retention of luminal contents and to facilitate water and electrolyte absorption
What is peristalsis?
a wave contraction that normally proceeds along the gut in the aboral direction and is triggered by the distension of the gut wall.
What is segmentation?
the mixing or churning movements caused by rhythmic contractions of the circular muscle layer that mix and divide the luminal contents.
What is tonic contractions?
sustained contractions found in sphincters of the GI tract
How is water absorbed from the lumen of the intestines?
by a passive process driven by the transport of solutes (mainly Na+) into the blood.
typical values of water entering the body and being absorbed?
9.3 litres enter the tract daily
8.3 litres absorbed by SI
1 litre enters LI with 90% of this absorbed and the other 10% excreted (100ml in faeces)
how much water, cellulose, bilirubin and bacteria in faeces?
100ml water, 50ml cellulose, bilirubin and bacteria
What is diarrhoea?
loss of fluid and solutes from GI tract in excess of 500mL per day
What is intestinal fluid movement always coupled to?
solute movement
two possible routes of movement for water?
transcellular or paracellular
Mechanism by which Na+ encourages the absorption of water?
1) Na+/glucose co-transport and Na+/amino acid (AA) co-transport are used to transport Na+, glucose and AA throughout the small intestines.
2) Na+/H+ exchange in the duodenum and jejunum
3) parallel Na+/H= and Cl-/HCO3- exchange in ileum and colon
4) epithelial Na+ channels (ENaC) transport Na+ in the distal colon.
What is the postprandial period?
relating to the 2hr period after eating dinner/lunch
When is the transport of Na+, glucose and AA most important?
in the postprandial period
What stimulates the Na+ and H+ exchange?
luminal HCO3-
when is the exchange of Na+, H+, Cl- and HCO3- most important?
in the interdigestive period
what regulates ENaC?
aldosterone
2 routes of absorption of Cl-?
transcellular and paracellular
How is Cl- absorbed in the SI?
the driving force produced by the negative potential of the lumen due to transport of Na+ via Na+/glucose and Na+/AA transporters
How is Cl- absorbed in the LI?
the driving force produced by the negative potential of the lumen due to transport of Na+ via ENaC.
2 other mechanisms of Cl- absorption?
1) via Cl-/HCO3- exchange in the ileum and the distal and proximal colon
2) via parallel Na+/H+ and Cl-/HCO3- exchange in the ileum and proximal colon
what is the difference in the rate of Cl- secretion and absorption?
rate of absorption is usually higher than the rate of secretion
what type of cells secrete Cl-?
crypt cells
three processes involved in the Cl- secretion on the basolateral membrane
1) Na+/K+ ATPase
2) Na+/K+/2Cl- co-transporter (NKCC1)
3) K+ channels (IK1 and BK)
Explain the mechanism of Cl- secretion.
1) the low intracellular Na+ drives the inward movement of Na+, K+ and Cl- via NKCC1
2) K+ leaves again via the K+ channels but the intracellular concentration of Cl- increases creating an electrochemical gradient for Cl- to exit the cell via CFTR (cystic fibrosis transmembrane regulator) on the apical membrane
3) The negative potential of the lumen develops hence providing a voltage-dependent secretion of Na+ through the paracellular pathway.
What causes secretory diarrhoea?
aka traveller’s diarrhoea
most common cause is E. Coli.
How does cholera cause secretory diarrhoea?
1) the cholera toxin enters the enterocyte
2) this enzymatically inhibits GTPase activity on the Gsα subunit
3) this increases adenylate cyclase activity
4) this increases cAMP concentration
5) cAMP stimulates CFTR
6) this results in the hypersecretion of Cl- with Na+ and water following.
What are the roles of GTPase?
Guanosine triphosphate plays an important role in:
1) signal transduction at intracellular domain of transmembrane receptors
2) protein biosynthesis (translation) at ribosome
3) control & differentiation during cell division
4) translocation of proteins through membranes
5) transport of vesicles within the cell
What does the Gsα subunit do?
activates the cAMP-dependent pathway by activating adenylyl cyclase
How does inhibiting GTPase acitivity on the Gsα subunit cause diarrhoea?
because it prevents the GTPase hydrolysing the G-protein so the Gsα subunit can stimulate cAMP causing more Cl- secretion.
Why is Cl- secretion usually minimal?
because the apical CFTR is either closed or not present
What activates CFTR to secrete Cl-?
1) bacterial enterotoxins
2) hormones and neurotransmitters
3) immune cells products
4) some laxatives
CFTR is activated as a result of the generation of second messengers such as…?
1) cAMP
2) cGMP
3) Ca2+
Cl- secretion via CFTR results from 2 things. What are they?
1) the opening of CFTR channels at the apical membrane
2) the insertion of channels from intracellular vesicles into the membrane
What does the Cl- secretion in the lumen cause?
1) Na+ paracellular secretion
2) Water secretion
(Overall, secretory diarrhoea)
What causes congenital chloridorrhoea? (a congenital defect)
the absence of Cl-/HCO3- exchanger
What causes infectious diarrahoea?
infections by enterotoxins from some strains of bacteria e.g. E.coli, salmonella, norovirus etc
What causes exudative diarrhoea?
inflammation and destruction of the intestinal absorptive epithelium
What types of diarrhoea are caused by impaired NaCl absorption?
1) congenital chloridorrhoea
2) infectious diarrahoea
3) exudative diarrhoea
How does hypermotility cause diarrhoea?
excessive peristalsis (contraction) of the GI with reduced reabsorption of solutes and water. (occurs in cases of Irritable Bowel Syndrome)
How does non-absorbable or poorly absorbable solutes in the intestinal lumen cause diarrhoea?
it causes water to diffuse into the lumen due to osmotic gradient (water potential gradient) resulting in osmotic diarrhoea.
(an example of this is in lactose intolerance)
Three electrogenic mechanisms of Na+ absorption that drives Cl- absorption?
Na+/glucose co-transport
Na+/AA co-transport
ENaC
What is lactose intolerance?
a digestive problem resulting from the inability to adequately digest lactose due to a lack in lactase enzymes
Why is there a variable degree of lactase persistence in the human population?
because of the polymorphism in the MCM6 gene regulating the expression of the lactase gene.
Lactose intolerance can result from three things. What are they?
1) primary lactase deficiency (primary hypolactasia)
2) secondary lactase deficiency
3) congenital lactase deficiency
What is primary lactase deficiency (primary hypolactasia)?
a lack of the lactase persistence allele
What is secondary lactase deficiency
damage to/ infection of the proximal small intestine
What is congenital lactase deficiency
a rare autosomal recessive disease- no ability to digest lactose since birth.
What happens when lactose is ingested by a patient with lactose intolerance?
the lactose can’t be broken don at the SI into galactose and glucose. So enters the LI and is broken down into:
- short chain fatty acids (which can be absorbed)
- hydrogen (which can be detected in the breath of lactase deficient individuals)
- CO2
- Methane
What are the symptoms of lactose intolerance if an individual ate a product containing lactose?
1) bloating
2) abdominal pain
3) flatulence
4) diarrhoea
How Is lactose intolerance diagnosed?
1) Hydrogen breath test
2) lactose/milk tolerance test
- association of symptoms with lactose consumption
How is lactose intolerance treated?
1) use milk that’s lactose-free
2) use milk products treated with lactase
3) reduce/eliminate consumption of milk products
What are the consequences of diarrhoea?
- dehydration (Na+ and H2O loss)
- metabolic acidosis (HCOm- loss)
- Hypokalaemia (K+ loss)
What organs are involved in causing diarrhoea?
SI or LI
Treat of diarrhoea?
- maintenance of fluid and electrolyte balance
- use anti-infective agent (if appropriate)
- use anti-motility agents
How does the rehydration therapy work?
1) 2 Na+ bind to Na+/glucose transporter
2) affinity for glucose increases so glucose binds
3) Na+ and glucose translocate from extracellular to intracellular environment
4) The 2 Na+ dissociate and from the Na+/glucose transporter making the affinity for glucose to drop
5) Glucose dissociates
6) The cycle is repeated
This cycle accompanied by the absorption of H2O
What do oral rehydration salts contain?
1) glucose
2) sodium chloride
3) trisodium citrate
4) potassium chloride
5) water, 1L
What do basic solutions contain?
1) glucose
2) salt
3) water, 1L
What are the actions of opiates on the alimentary tract?
1) inhibition of enteric hormones
2) decrease peristalsis, increase segmentation (constipation)
3) increase fluid absorption
4) constrict pyloric, ileocaecal and anal sphincters
Major opiates used in diarrhoea?
1) codeine
2) diphenoxylate - has antisecretory effect
3) loperamide - selective for GI tract and reduces cramp and passage of faeces.
What is constipation?
difficult and infrequent defecation
Examples of causes of constipation?
1) neurogenic disorders of LI leading to reduced peristalsis
2) abdominal muscle weakness
3) diet poor of fibres
4) sedentary lifestyle
5) constant suppression of the urge to empty
6) antidepressant drugs (anticholinergics)
7) opiates
8) aging
Purgatives used to treat constipation?
1) bulk laxatives
2) osmotic laxatives
3) faecal softners
4) stimulant laxatives (directly increase peristalsis)
Drugs used to treat constipation without purgation?
antiemetics - increase GI motility and gastric emptying
What is purgation?
Emptying/cleansing of bowels by the use of laxatives
