Large Intestine, Constipation, Diarrhoea + Lactose Intolerance Flashcards
What does the longitudinal muscle do?
Lumen becomes shorter + fatter
= facilitate movement of food
What does the circular muscle do?
Narrower + longer
What does the muscularis mucosae do?
Change in absorptive + secretory area of mucosa
What are the 2 plexuses in enteric nervous system?
Myenteric
Submucosa
What is the enteric nervous system comprised of?
Sensory neurons then interneurons then effector neurons
What are the sensory neurons?
Mechanoreceptors, chemoreceptors + thermoreceptors
What are the interneurons?
Co-ordinate reflexes + motor programs
What are the effector neurons?
Excitatory + inhibitory motor neurons
What is involved in autonomic innervation of GI?
Parasympathetic + sympathetic
What are the excitatory influences of parasympathetic?
Increase gastric secretion, blood flow + smooth muscle contraction
What are the inhibitory influences of parasympathetic?
Relaxation of sphincters
Receptive relaxation of stomach
What does the parasympathetic not have?
Discrete ganglia = found on target organ
What does the sympathetic do?
Inhibitory influences
= decrease motility, secretion + blood flow
What is functionally more important parasympathetic or sympathetic?
Parasympathetic
What is smooth muscle in GI tract capable of + why?
Spontaneous contraction
= contract as one big cell
= joined by gap junctions
What is spontaneous activity of smooth muscle in GI tract modulated by?
Intrinsic (enteric) + extrinsic (autonomic) nervous system
Hormones
What does spontaneous electrical activity occur as?
Slow waves
What are slow waves driven by?
Interstitial cells of Cajal (ICCs)
= pacemaker cells
Where are ICCs located?
Between longitudinal + circular muscle layers in submucosa
What do slow waves determine?
Basic electrical rhythm
What does it depend on that slow waves reach threshold?
Neuronal stimuli
Hormonal stimuli
Mechanical stimuli
What is peristalsis?
Series of wave-like muscle contractions that move food through digestive-tract triggered by distention of gut wall
Involves longitudinal muscle layers
What is segmentation?
Rhythmic contraction of circular muscle layer that mix + divide luminal contents
What do circular muscle do?
Make lumen smaller = squeeze food = break large bits apart
What is the absorption of water driven by?
Transport of Na+
Passive process
What is diarrhoea defined as in terms of water loss?
Excess of 500 ml per day
How may water move?
Paracellularly = through tight junction
Transcellularly = through cell
Describe Na+/glucose co-transport mechanism for H2O movement
Electrogenic
Small intestine
Describe Na+/amino acid co-transport mechanism for H2O movement
Electrogenic
Small intestine
Describe Na+/H+ co-transport mechanism for H2O movement
Electroneutral (powered by presence of bicarbonate)
Duodenum + jejunum
Describe parallel Na+/H+ + Cl-/HCO3- co-transport mechanism for H2O movement
Electroneutral
Ileum + colon
Describe epithelial Na+ channel mechanism for H2O movement
Electrogenic
Distal colon
Why is something electrogenic?
Na+ goes to blood
= makes blood more positive
= creates electrical charge
What is something electroneutral?
Na+ goes in
H+ comes out
= NO change in electrical charge
When is Cl- also reabsorbed?
IN ALL OF THEM
Describe Cl- secretion
Occurs at basal rate
From crypt cells
Important in diarrhoea
What happens in basolateral membrane mechanism of Cl- secretion?
Na+, K+ + Cl- enter by co-transport
Cl- enters lumen through CFTR channel
Na+ reabsorbed
Cl- attracts Na+ via paracellular = H2O follows
What are CRTF channels normally?
Closed
What are CFTR activated by?
Bacterial enterotoxins
Hormones + neurotransmitters
Immune cell products
Laxatives
What is the role of CFTR in diarrhoea?
Activation = generation of 2nd messengers
What are the 2nd messengers?
cAMP
cGMP
Ca2+
What is secretory diarrhoea?
Secretion of Na+, Cl- + H2O
What is the 1st cause of secretory diarrhoea?
Excessive secretion
= caused by E.coli
How does cholera cause secretory diarrhoea (excessive secretion)?
GDP goes to GTP
= subunit dissociates
Cholera toxin inhibits activity of GTPase activity of subunit
What may also cause secretory diarrhoea (excessive secretion)?
Increased activity in adenylate cyclase
Increased conc of cAMP
cAMP stimulates CFTR
Hypersecretion of Cl-, Na+ + H2O
What is the 2nd cause of secretory diarrhoea?
Impaired absorbance of NaCl
= caused by congenital defects
What is 3rd cause of secretory diarrhoea?
Non-absorbable/ poorly absorbable solutes
= lactose intolerance
What is 4th cause of secretory diarrhoea?
Hypermotility
= excessive peristalsis of GI
What are the consequences of diarrhoea?
Dehydration
Metabolic acidosis
Hypokalaemia
What is the treatment process for diarrhoea?
Maintain fluid balance (1st)
Anti-infective agents (if appropriate)
Anti-motility agents
How does rehydration therapy work?
2 Na+ bind
Affinity for glucose increases
Na+ + glucose translocate to intracellular
2 Na+ dissociate, affinity for glucose falls
Glucose dissociates
Cycle repeated
What do anti-motility drugs do?
Decrease motility in gut
What can opiates do?
Anti-diarrhoeal activity
= inhibit enteric neurons
= decrease peristalsis, increase segmentation
What are the major opioids used in diarrhoea?
Codeine
Diphenoxylate
Loperamide - 1st choice
Atropine
What are problems with codeine?
NOT very selective
= CNS activation
What are the problems with atropine?
Anti-muscarinic
= decrease parasympathetic activity
= decrease motility
BUT not selective
Why is loperamide 1st choice?
Relatively selective to GI tract
Increases segmentation, decreases peristalsis
What is lactose intolerance?
Lactase deficiency
What is primary lactase deficiency?
Lack of lactase persistence allele
What is secondary lactase deficiency?
Damage to proximal small intestine
What is congenital lactase deficiency?
Rare autosomal recessive disease
= from birth
When does hypolactasia cause a problem?
Lactose-containing food is consumed
Describe process of lactose intolerance
NOT digested in small intestine
= goes to large intestine
= bacteria convert it to H gas + fatty acids
= attract H2O
How is diagnosis done for lactose intolerance?
Diet observation
How is lactose intolerance treated?
Reduction or elimination in lactose-containing food
What are the causes of constipation?
Neurogenic disorders of large intestine
Abdominal muscle weakness
Diet poor of fibre
Aging
Why do neurogenic disorders of large intestine cause constipation?
Reduce peristalsis
eg. IBD, cancer
How do you treat constipation?
Changes in lifestyle
More H2O, less alcohol
Increase activity
Improve toilet routine = keep tp regular time
What drugs can be used to treat constipation?
Laxatives
Antiemetics
What laxatives can be used to treat constipation?
Bulk laxatives
Osmotic laxatives
Faecal softeners
Stimulant laxatives
Why can antiemtics be used to treat constipation?
Increase motility + gastric emptying
