lecture 9

Question 1

classifications of diarrhoea

Answer 1

acute <2wk
persistant >2wk
chronic>30dy

Question 2

inflammatory diarrhoea caused by

Answer 2

presence of imflammatory process(eg virus/bacteria/parasitic infection)

Question 3

symptoms of inflammatory diarrhoea

Answer 3

mucoid (jelly like substance) and blood in stool, sudden urge( tenesmus), fever, crampy abdominal pain, small frequent bowel movements (>3 per dy)

Question 4

what is a sign of inflammation in the GIT

Answer 4

leucocytes

Question 5

non-inflammatory diarrhoea symptoms

Answer 5

watery , large volume and frequent stools (10-20 a day)

Question 6

histology of GIT effected in what

Answer 6

inflammatory diarrhoea

Question 7

osmotic diarrhoea

Answer 7

water is drawn into the lumen of the GIT due to poorly absorbed material (eg Mg or manitol)which draws water in, small stool vol vs secretory

Question 8

how to stop/improve osmotic diarrhoea to test

Answer 8

fasting stops it

Question 9

secretory diarrhoea

Answer 9

altered transport of ions across the mucosa which causes increased secretion and decreased absorption of fluids. This will not improve with fasting

Question 10

Most common cause of acute diarrhoea (UK) is

Answer 10

bacteria (usually in food)- e coli, salmonella, c diff, listeria, vibro cholerae

can also be due to viruses/parasites - rotavirus/norovirus/adenovirus or Giardia lamb/cryptosporidium

Question 11

causes of non infectious diarroea

Answer 11

medication
cardio - digoxin/propanolol/aceinhibits/quinidine
GI- antacids/laxatives/h2 antagonists
endocrine- oral hypoglycaemic/thyroxine
antibac - amoxicillin/ cephalosporins/erythromycin

Question 12

what is the main source of absorption from the lumen

Answer 12

enterocytes - microvilli increases the surface area which increases absorption

Question 13

if electrolytes/glucose enters the apical membrane of the enterocyte water_____

Answer 13

follows

Question 14

function of tight junctions

Answer 14

so that substances (eg unwanted/big) dont pass through

Question 15

how does water cross the membrane

Answer 15

aquaporins - can’t diffuse since its hydrophilic

Question 16

how does increased ion secretion into lumen cause diarrhoea

Answer 16

because more water goes with the ions into the lumen

Question 17

why can sodium move through tight junctions

Answer 17

because of its positive charge it can move through due to the increasing -ve cl ions through to the other side

Question 18

antibacterial effect on motility

Answer 18

distrupts normal microflora allowing proliferation of opportunistic pathogens (c diff) leading to impaired fermentation of poorly absorbed carbs/reduced production of short chain fatty acids because the good bacteria usually breaks this down so more fluid goes through and isnt absorbed

Question 19

drug treatment for uncomplicated acute diarrhoea

Answer 19

antimotility drugs- prolonge duration of intestinal transit

Question 20

diphenoxylate targets___ to activate ___ leading to ____

Answer 20

mui opioid receptors on neuronal variscosities , activating opioid receptors. This decreases Ach release so reduces peristaltic activity and increases segemntal contraction

Question 21

what is diphenoxylate given in combination with

Answer 21

atropine ( co-phenotrope)

Question 22

what does diphenoxylate treat

Answer 22

diarrhoea

Question 23

codeine phosphate is for

Answer 23

releif of chronic diarrhoea - similar mechanism of action to diphenoxylate

Question 24

adverse effects of opioiates

Answer 24

rebound constipation, CNS effects with high doses , opioid dependence in prolonged use

Question 25

racecadrotril activates______ which______

Answer 25

activates delta opioid receptors to decreace cellular cAMP. This decreases cl secretion so also decreases water secretion - racecadrotril is a prodrug so its broken down to thiorphan . thiorpan is an enkephalinase inhibitor (treats diarrhoea)

Question 26

what are enkephalins

Answer 26

endogenous activator of sigma opioid receptors

Question 27

what is the effect of the toxin produced by bacteria

Answer 27

it enters enterocides and activates a g protein which is coupled to adenylyl cyclase - convertinf cAMP to PKA. This phosphorylates the calcium channel - allowing more chlorine to exit the enterocyde into the lumen - wter follows the chlorine. cAMP also inhivits the sodium hydrogen exchanger so the sodium isnt getting absorbed leaving more in the lumen.

Question 28

how does cholonergic activity effect motility

Answer 28

actiates cholinergic receptors on the smooth muscle this increases the transit time - so less absorption occurs

Question 29

anticholinesterases do what

Answer 29

stimulate smooth muscle because the ach has a longer effect

Question 30

simplified racecadrotril effect

Answer 30

anti secretory drug which prevents cloride ion secretion. The delta opioid receptor activation is usually by enkephalins which decreases cAMP - so theres no phosphorylation of chloride channel ( decreased chloride ion secretion and therefore less water in lumen)

Question 31

constipation caused by

Answer 31

pelvic floor dysfunction , IBS, medication , metabolic/endocrine disorders, anxiety/depression etc

Question 32

drug induced constipation caused by

Answer 32

drugs with anticholinergic activity eg antidepressants/histamine/muscarinic/psychotic/parkinson opioids laxative misuse -

Question 33

what does laxative misuse lead to

Answer 33

atonic colon

Question 34

linaclotide mechanism of action

Answer 34

binds to receptors which activate GCC- this increases intracellular cGMP abd activates PKG which phospholylates cloride channel. This increases the efflux of cl and water out into the lumen (treats constipation)

Question 35

adverse effects of linaclotide

Answer 35

diarrhoea, nausea, vomiting and abdominal pain