diarrhoea Flashcards
inflammatory diarrhoea
- can be due to viral/bacterial/parasitic infection, radiation injury or IBD
- mucoid and bloody stool, tenesmus, fever, crampy abdominal pain
- small, frequent bowel movements
non-inflammatory diarrhoea
- watery, large volume, frequent stool
- no tenesmus, blood in stool, fever or faecal leukocytes
osmotic diarrhoea
- presence of unabsorbed or poorly absorbed solute
- stool volume is small
- stops/improves with fasting
- due to maldigestion/malabsorption
secretory diarrhoea
- altered transport of ions across mucosa
- increased secretion and decreased absorption of fluids
- doesn’t improve with fasting
causes of infectious diarrhoea
bacteria:
- E. coli, campylobacter, salmonella, C. diff, listeria, vibrio cholerae
viruses:
- rotavirus, norovirus, adenovirus, astrovirus
parasites/protozoa
- entamoeba histolytica, giardia lamblia, cryptosporidium
causes on non-infectious diarrhoea (medication)
cardiovascular drugs:
- digoxin, quinidine, propranolol, ACE inhibitors (enalapril/ramipril)
GI drugs:
- antacids, laxatives, H2 antagonists
endocrine system drugs:
- oral hypoglycaemic agents, thyroxine
anti-bacterials:
- amoxicillin, cephalosporins, erythromycin
physiology of small intestines
- small intestine majority of absorption and secretion occurs
- water follows the movement of electrolytes/glucose
- enterocytes are intestinal absorptive cells (columnar epithelial cells) found along the large/small intestine
- epithelial cells are polarised cells
- membrane across from lumen is apical membrane
- membrane facing the interstitial fluid is the basolateral membrane
mechanisms causing diarrhoea
- caused by increased secretion or decreased absorption of solutes
- sodium and chloride transport is central to diarrhoea caused by bacteria
Cl- transport in the intestine
- secreted Cl- (from enterocytes) is provided by the Na+/K+/2Cl- cotransporter
- activity is driven by low intracellular Na+
- Cl- is secreted through Cl- channels
- Na+ and water enter lumen by paracellular transport
vibrio cholerae
- cholera toxin from vibrio cholerae enters cells
- activates G protein which activates adenylyl cyclase
- increases cellular cAMP and activation of protein kinase A
- phosphorylation of Cl- channel
- increases efflux of Cl- (and water)
- diarrhoea occurs
drug treatment of diarrhoea
- antimotility drugs - prolong duration of intestinal transit by binding to opioid receptors in the intestine
- diet and oral rehydration sachet
- parenteral rehydration therapy if severe
- antibiotic may be given if organism identified
- loperamide (opioid antagonists) antimotility drug
diphenoxylate
- mu opioid receptors on neuronal varicosities
- activation of opioid receptors on presynaptic nerves inhibits Ach release
- decreases GI motility and also intestinal secretion
- has inhibitory effects on intestinal smooth muscle contractility
- stimulate relaxation of the longitudinal muscle
- increases segmental contraction and decreases peristaltic activity thus increasing the intestinal transit time
- usually provided as a mixture with atropine to discourage overdose/injection
codeine phosphate
- opiate used to treat pain and diarrhoea caused by IBD
- symptomatic relief of chronic diarrhoea
- mechanism of action similar to diphenoxylate
adverse effects of opiates
- rebound constipation
- higher doses can have CNS effects
- prolonged use can lead to opioid dependence
raecadotril
- activation of delta opioid receptors decreases the cellular cAMP level
- decreases secretion of Cl- into lumen as well as water
- enkephalins are the endogenous activator of delta opioid receptors
- enkaphalinase enzyme responsible for breaking down enkephalins
- thereby reliving the inhibitory effect it has on the chloride ion channels
- it is a prodrug metabolised to thiorphan
- thiorphan is an enkaphalinase inhibitor
