Physiology and Pharmacology of fluid balance and motility in the GIT Flashcards
Typically how much water is absorbed by the small intestine?
8.3 litres
Typically how much water is absorbed by the large intestine?
1 litre enters the large intestine - of which 90% is absorbed
What do faeces normally contain?
100ml of water
50ml of cellulose, bilirubin and bacteria
What is diarrhoea defined as?
Loss of fluid and solutes from the GI tract in excess of 500ml per day
What kind of process is absorption of water in the GI tract?
Passive process
What is absorption of water in the GI tract driven by?
The transport of solutes (Particularly Na+) from the lumen of the intestines to the bloodstream
Driven by the reabsorption of Na
How might water move in the GI tract?
Via transcellular or paracellular routes
What does reabsorption of NA+ provide?
Provides an osmotic force for reabsorption of water through cells into vascular capillaries inside villi
What are the major mechanisms of postprandial Na absorption in the small intestine?
Na+/amino acid co-transport
Na+/glucose co-transport
Describe the 2 co-transporters in the small intestine?
They are secondary active transport
They are electrogenic - collectively the transport of NA+ generates a transepitheial potential in which the lumen is negative (this drives the parallel absorption of Cl-)
Are either of the Na+/glucose and Na+/amino acid cotransport regulated by intracellular cAMP or Ca?
No neither are regulated by intracellular cAMP or Ca
Describe some infections of the GI tract causing diarrhoea?
Viral, bacterial, parasitic
Campylobacter jejuni - commonest strain of bacteria causing gastroenteritis in the UK
Travellers diarrhoea - (enterotoxin producing E.Coli) the most frequent cause
Describe some non-infectious causes of diarrhoea?
IBD, IBS, bile-salts excess, Lactase def.
Psychological factors –anxiety, depression
Hyperthyroidism
Drug induced – Magnesium salts, Cytotoxic drugs, Betablockers
What can lead to C.diff colitis?
Borad spectrum antimicrobials
What part of the GI tract does diarrhoea involve?
Can involve the small or large intestine
Describe excessive section as a cause of diarrhoea?
Caused by cholera toxin (commonly)
cholera toxin enters enterocyte
enzymatically inhibits GTPase activity of the Gs subunit
increased activity of adenylate cyclase
increased concentration of cAMP
cAMP stimulates CFTR
hypersecretion of Cl-, with Na+ and water following
Describe rotavirus as a cause of diarrhoea?
Causes inhibition of Na/K/ATPase and structural damage to mucosal cells leading to reduced absorption
What can diarrhoea result in?
dehydration (Na+ and H2O loss)
metabolic acidosis (HCO3- loss)
hypokalaemia (K+ loss)
may be fatal if severe (e.g. cholera)
What might be some treatment options of severe acute diarrhoea?
maintenance of fluid and electrolyte balance (1st line- life saving)
use of antimicrobial agents (severe infective cases only)
use of antimotility and spasmolytic agents (symptomatic relief in selected cases)
When do you need to give IV rehydration in diarrhoea?
When fluid loss is severe (>10% body weight)
When would oral rehydration therapy be sufficient and describe it?
IT would be sufficient in the majority of cases
It is not designs to stop diarrhoea, it is used to restore and maintain hydration till diarrhoea stops
What is gastroenteritis?
Infectious diarrhoea - inflammation of the GI tract that involves stomach and small intestine
Describe the mechanisms of rehydration therapy and the SGLT1?
2 Na+ bind
Affinity for glucose increases, glucose binds
Na+ and glucose translocate from extracellular to intracellular
2 Na+ dissociate, affinity for glucose falls
Glucose dissociates
Cycle is repeated
What remains intact even insecure gastroenteritis?
Glucose facilitated Na absorption in ileum remains intact
What do oral rehydration salts contain?
Glucose 20 g
Sodium chloride 3.5 g
Sodium bicarbonate 2.5 g
Potassium chloride 1.5 g
Dissolved in a volume of 1 L drinking water
What causes accompanying absorption of H2O?
Absorption of Na and glucose by SGLT1
What is SGLT1?
Sodium Glucose Transport proteins
Describe antimicrobials in the management of diarrhoea?
Limited role as most are vial in origin and most bacterial diarrhoea’s resolve spontaneously
They are useful in severe disease
Name some antimicrobials used in the management of diarrhoea?
Cotrimoxazole
Erythromycin
Ciprofloxacin/ Norfloxacin
Doxycycline
What might you give in C.diff colitis?
Metronidazole (oral/IV)
Vancomycin (oral)
What might anti-motility agents be used for in diarrhoea?
Used for symptomatic relief in uncomplicated acute diarrhoea in adults
When is anti-motility agents contradicted?
In acute infective diarrhoea’s, IBS, IBD, diverticulosis
What are examples of anti-motility agents?
Opioids drugs - constipating effect
What do the actions of opiates on the alimentary tract include?
inhibition of enteric neurones (hyperpolarization via activation of -opioid receptors)
decreased peristalis, increased segmentation (i.e. constipating)
increased fluid absorption
constriction of pyloric, ileocaecal and anal sphincters
increased tone of large intestine
What are the main opiates used in diarrhoea (anti-motility)?
Loperamide
Diphenoxylate
Codeine
Describe loperamide?
Relatively selective for GI tract, low CNS penetration (less dependence) undergoes enterohepatic recycling
Additional weak antimuscarinc effect
Longer acting, more effective and suitable than other opioids
Describe diphenoxylate?
Low CNS penetration
Many preparations contain atropine
Describe codeine?
Central effects
Low dependence liability
Describe recacadotrill?
Newer agent
A pro-drug of thiorphan
An enkephalinase inhibitor inhibits the breakdown of endogenous opioids & reduces intestinal secretions.
Used in children over 3 months of age as an adjunct to rehydration (loperamide/ diphenoxylate are contraindicated in children)
Not SMC approved for use in Scotland.
What is the definition of consitpation?
Infrequent production of hard stools requiring staring to pass or a sense of incomplete evacuation
What might cause constipation?
Ignoring, or suppressing the urge to defecate
Decreased colonic motility (e.g. improper diet, drugs, metabolic disorders, old age)
Lack of exercise/sedentar lifestyle
Impairment of motility/defeacation reflex (e.g. Hirschprung disease, involving absence of a section of the enteric nervous system)
What do laxative produce?
A milder action resulting in passage of soft but formed stools
What do purgatives produce?
A stronger action leading to more fluid evacuation
When should laxative and purgatives?
Neither should be used when there is a physical obstruction to the bowel
What is laxative dependency due to?
Development of atonic colon
Describe bulk laxatives?
Indigestible polysaccharide polymers
e.g. methylcellulose
Improve stool consistency. Slowly acting.
Water by osmosis is attracted to the stool increasing bulk and stimulating peristalsis.
Describe stimulant purgatives?
e.g. bisacodyl, senna
Increases the water and electrolyte secretion from the colonic mucosa. Colonic content is increased stimulating peristalsis
Abdominal cramps are common
Describe osmotic laxatives?
Poorly absorbed solutes. Increase bulk and stimulate peristalsis.
Rapidly acting. Lactulose orally.
(most people are on this kind)
Describe faecal softners?
Detergent like action
Describe valid clinical indication of laxatives?
Straining will exacerbate the condition (hernia, angina, eye surgery)
Increase risk of rectal bleeding or when defecation painful (anal fissures, haemorrhoids)
Drug-induced constipation (opioids)
Bedridden patients (MI, strike, fractures, posted)
For the expulsion of parasites after anthelmintic treatment
To prepare the alimentary tract before surgery and radiological procedures