GI exam 1

what is the enteric nervous system

third division of autonomic nervous system, in wall of GI tract, capable of autonomous functions separated from CNS, myenteric plexus located between circular and longitudinal muscle layer and meissner’s plexus is located in the submucosa (regulates secretion, fluid transport and blood flow)

how does the stomach move

Ach causes everything to constrict but serotonin controls it as it causes some of the muscle to contract and others to relax so that shit can move called peristalsis

what is the role of serotonin

enterochromaffin cells release serotonin to initiate gut reflexes by acting on enteric neurons, excessive release of serotonin induces vomiting and targeting the serotonin system is an important strategy for modulating motility secretion and emesis

what is the role of dopamine

dopamine inhibits motility by suppressing Ach through D2 receptors so Da receptor antagonist increase motility by blocking suppression og ACh release, lowers esophageal sphincter and gastric pressures also relive nausea and vomiting

what are prokinetic agents and stimulants of GI contractility

Metoclopramide has dual action of 5HT4 agonism and DA receptor antagonism effects are mainly confined to upper GI tract as it increase esophageal sphincter tone and stimulates upper Gi contractions other examples are Cisapride (5HT agonist 5ht3 antagonist) procilopride (5ht4 agonist constipation), and alosetron (5HT3 antagonists IBS)

what is the key idea behind secretory agents for GI motility

fluid follow ions, prostaglandins regulate ion channels, high ion levels in intestine will bring fluids into intestinal lumen which increases motility

what is lubiprostone

Used for constipation interacts with the EP4 (prostaglandin E1 binds here) receptor leading to increase Chloride release through CFTR into the lumen leading to increase water in the lumen (increase volume softens stool) and increased bowel movement only acts in the lumen

what is linaclotide and plecanatide

stimulate secretions into the GI by acting as agonist of guanylate cyclase C which elevates cGMP and elevated cGMP stimulates secretion of chloride and bicarbonate and water into the intestinal lumen does not get absorbed systemically and are degraded by intestinal enzymes

what is pepto bismol

react with HCL in the gut to give salicylic acid and bismuth chloride, the bismuth stays in the GI tract and salicylic acid is absorbed systemically it has anti secretory action by stimulation of absorption of fluids and electrolytes by the intestinal wall treating diarrhea

what is fiber

bulk sotness and hydration of feces depends on fiber content foal is to increase bulk with associated water and it is the part of food that resists enzymatic digestion and reaches colon largely unchanged

what is unfermentable fiber

attracts water and increases stool bulk

what is fermentable fiber

colonic bacteria ferment some carbohydrate based fibers to different degrees, the fiber attracts water and increases bulk entering colon, fermentation produces short chain fatty acids that are trophic for colonic epithelium and have a prokinetic effect, and increases bacterial bio mass increase stool volume dose increase gas production

what are SCFAs

acetate propionate and butyrate increase gut motility and secretory activity are short chain fatty acids

what is stimulating soluble fiber

carbohydrates that are not digested in stomach or intestine by humans but are digested by bacteria , fermented by bacteria in colon to give SCFAs and gasses, increase volume water content and biomass of stool, example is hemicellulose , mucilages and gums (can have some non-soluble fiber), and wheat dextrins, pectins

what is non-stimulating fibers

do not produce SCFAs, example is methylcellulose is more water soluble that cellulose not enzymatically hydrolyzed leading to no fermentation absorbs large amount of water into colon as bulk forming laxative, and calcium polycarbophil has similar effects does not produce gas

what is lignin

cross-linked phenolic polymer found in plants that is not digested by humans nor fermented by colonic bacteria and insoluble and swells upon hydration

what are osmotically active laxatives

nondigestible sugars and alcohol lactulose is synthetic gets broken down into acetate and lactate producing fermentation or sorbitol and mannitol which are also degraded in short chain fatty acids or miralax which passes unchanged as PEG and increases water content

what are saline laxatives

magnesium derivates as magnesium is poorly absorbed from the GI tract, so it increases electrolyte content in the GI leading to increase water being drawn into the intestine examples are milk of magnesia, mag sulfate, and mag citrate

what is stool wetting agent and emollients

docusate salts is an anionic surfactant that lowers surface tension of stool to allow mixing of aqueous and fatty substance softening the stool, reduces amount of water resorbed from the stoll and stimulates intestinal fluid and electrolyte secretion

what are stimulant (irritant laxative)

Bisacodyl salts and anthraquinones (senna has a complex stimulating effect) as they have direct effects on enterocytes enteric neurons and GI smooth muscle to promote accumulation of water and electrolytes and stimulate intestinal motility oral and suppository

what are the basic agents for peptic ulcer and GERD

H+ is secreted by parietal cells, mucus and bicarbonate secreted by superficial epithelial cells, proton pump pumps H+ into cells is inhibited by PPIs, H2 receptor stimulates acid secretion in partial cells is blocks by H2 antagonism, adn potassium completive acid blockers may be effective but limited availability and misoprostol inhibits acid secretion by inhibiting EP3 which prostaglandins bind to

what do PPIs do

inhibit H+K+ ATPase or proton pumps are bioactivated under acidic conditions must be absorbed systemically to work

what is H2 receptor antagonist

structural analogs of histamine reversible compete with histamine blocking cells work for 24 hours mainly inhibit basal acid secretion can have tolerance examples are famotidine and ranitidine

what are agents that enhance mucosal defense

misoprostol acts in past of prostaglandin at EP3 site and sucralfate neutralizes acid in the GI tract and forms and protective film/paste over ulcers

what are the main factors of the stomach

excretes HCL pepsin and mucus, surface area to volume is 1-1, ph is 0.5-3.5 volume is 50-1500 and flow rate is 0-20 ml/min

what is main factors of the duodenum

liver, gallbladder and pancreases excrete here, excrete bicarbonate, organic waste products and enzymes, length is 20-30 cm, surface area to volume is about 250, ph is 5-7, volume is 25-75, flow rate is 4-6

what are main factors of the jejunum

length 150-250, surface area/volume is about 250, ph 6-7, volume is 50-500, and flow rate is 0.5-30

what is the ileum

200-300 length, surface area to volume is 100, ph is 7, volume is 50-500 and flow rate is 0.15-3.4

what physicochemical factors determine whether or not a drug will be well absorbed

how polar or lipophilic is a drug, what is the drugs pKA and is it ionized in the Gi tract, what is the molecular weight idea is under 500 Da, is the dose soluble in GI fluids

what is gastric secretions

HCL secreted by the parietal cells in the gastric mucosa fasted statew ph is 2.5 in females and 2 in males, basal secretion is 1-3 mEq/hr and maximum is 18 in females and 23 in males

what is HCL secretion in the fed state

ph increase to approximately the pH of the meal but drops back to basal level within one hour, then ph drops below basal following 2-3 hours due to continues HCL secretions

what is the fasted ph of the small intestine compared to feed

duodenum is 5.5-6.5, jejunum is 5.5 and ileum is 6.3 in fasted state, fed state duodenum is 5.7 in the first 30 minutes, then 4.6 until 4 hours after meal, jejunum is 5-6 and ileum is 7-7.5

what is gastrointestinal motility

substance move along the GI tract as the result of the contraction of longitudinal and circular smooth muscle, rate of movement depends on if the patient is feed or fasting state movement is mediated by receptors in the GI tract or contents of the stomach signally various receptors to modify GI motility

what is gastric motility in fasted state

cycles between quiescence with minimal activity, then phase II intermittent irregular contractions, the phase three a short period of intense contraction occurrence of the interdigestive migrating myoelectric complex (IMMC) removes large indigestible solids from stomach the IV transitions from phase III to I cycle take about two hours during fasted state is how sometablets move if cant be broken down

what is gastric motility patterns in the fed state

reduce food size to semi-liquid matter needs particles <1.5 mm in diameter to empty from the pylorus need 200 ml to induce feed state and max rate of emptying is 20ml/min, and is proportional to the volume of the contents in the stomach high fate solid meals increase retention time and gastroparesis if particle size below 1.5 it can get ride of it in under 4 hours if bigger takes 8 hours

what is intestinal motility patterns in the fasted state

IMMC velocity is 6-12 cm.min in duodenum and 1-3 cm./min in ileum, segmental movement is 40cm in the duodenum 30 cm in jejunum, 15 to 10 in the ileum

what is intestinal motility in the fed state

has two types of movement one is concentric contraction approximately 3cm region of the small intestine occuring 12-9 times movement and mixing occur in both a forward and retrograde direction, and the other movement is short periods of coordinated contractile activity over lengths of approximately 15 cm

what is signalling motility pattern changes

ileo-gastric reflex inhibits gastric emptying when ileum contains nutrients, gastro ileal reflex increased contractile activity in the ileum when food is present in the stomach

what is transit time through the small intestine

1 mm pellet with light meal is 2.4 hours if heavy meal 8.5 hours, tablet is 2.8 hours with light meal and 3.6 hours with heavy meal

what is residence time in the GI tract

= volume of the GI segment / flow rate mean residenct time in the small inestine ranges between 2-6 hours and stomach is 2-3 hours and normal full time is 40 hours meaning ¾ of residence time is in the large intestine

what is gastro retentive tablets

have hydrogels that swell in the stomach and slowly release medicine over several hours

what is food effect on the GI physiology

increase viscosity of luminal contents, slows gastric emptying. elevates post-prandial pH, increases splanchnic blood flow leading to increase absorption rate and may increase first past metabolism, increase bile salt secretion and lymphatic distribution, and competition with or upregulation of transporters

what is the effect is a high fat meal on bioavailability

retards gastric emptying, increases absorption of lipophilic drugs through enhanced solubilization induces bile salt secretion, increases absorption of bile sale micelles, effect is saturable, decrease absorption due to reduced partitioning, may inhibit epithelial efflux transport

what are effects of a high protein meal

compete with drugs that use amino acids, dipeptide and other epithelial transporters, can stimulate transporter upregulation and can increase hepatic enzymatic activity

what are effects of a high fiber meal

drug absorption to fiber contents

what is ciclosporin formulations

use ot be cyclosporine with corn oil and ethanol solution had high variability with fatty meals new formulation of microemulsion is pretty much the same with or without fatty meal

what is gastric emptying effect on enteric coated aspirin

non fasting delayed effect of regular aspirin, enteric coated tablets it leads to a significant delay in effects and enteric coated granules it has almost no effect n

what is GI peptide absorption

need to take on an empty stomach with less than 4 ounces of water as SNAC can be diluted and induces fed state absorption is increased gastric residence time

what is GLP-1 effect on GI

decreased GI motility affect tmax Cmax and AUC has not be found to be clinically relevant typically first dose of a new drug tends to cause most dramatic shift can take meds prior to admission to limit effects

what is achlorhydria

absences of HCL in gastric secretions is ph over 5 in men and 6.8 in women may be due to age, autoimmune disease chronic H. pyloric infection and PPI therapy

what other factors must be taken into consideration for GI motility

Ostomy bag can not use er tablets that sit in the colon and watch out for gastric bypass

what hormones effect appetite and energy balance and their effects

leptin decreases appetite and increases energy expenditure, Ghrelin increase appetite, and HLP-1 decreases appetite and increase insulin release

what is orlistat

lipase inhibitor stops lipase from breaking down lipids resulting in decrease lipid absorption and oily stool may increase number of times to the bathroom

what are the main anorexiants

Phentermine, phendimetrazine, diethylpropion and phentermine with topiramate are adjuvants in weight reduction programs have potential for abuse and are similar to amphetamines MOs is increasing NE and DA which results in decreased appetite Fen-Phen was taken off the market do to fenfluramine causing cardiotoxicity through 5HT2B agonism

what is bupropion and naltrexone

used as an anorexiant is an adjuvant in weight reduction program, decreases in appetite are due to release of a-MSH (bupropion and opioid antagonism stimulates proopiomelanocortin receptors which decrease appetite and increase NE and DA bupropion is metabolized by 2B6 and inhibits 2D6 caution

what is liraglutide

is a GLP has a glu added to bind to albumin to increase half it decrease weight by stimulating GLP-1 receptors in the brain to causes appetite suppression, stimulates insulin secretion and decreases glucagon secretion half life is 13 hours

what is semaglutide

it decrease weight by stimulating GLP-1 receptors in the brain to causes appetite suppression, stimulates insulin secretion and decreases glucagon secretion, half life is 7 days as it binds to albumin and is resistant to proteases

what is tirzepatide

it decrease weight by stimulating GLP-1 receptors in the brain to causes appetite suppression, stimulates insulin secretion and decreases glucagon secretion as well as a GIP receptor agonist which increases appetite suppression in the brain, stimulates insulin secretion but no effect on glucagon half life is 120 hours

what is setmelanotide

adjunct in weight loss programs, is a MC4 agonist it is a structural analog of a-MSH best useful in genetic condition such as POMC PCSK 1 or leptin receptor deficiency causes reduced hunger and decreases energy intake t half 11 hours

what is an ascites

accumulation of an excessive amount of fluid within the peritoneal cavity, treat with furosemide or spironolactone

what is portal hypertension

presence of a gradient of greater than 5 mm HG between the portal and central venous pressures treat with propranolol, or nadolol

what is hepatic encephalopathy

metabolically induced functional disturbance of the brain, use lactose to lower ammonia, to reduce GABA use flumazenil and bromocriptine for D2 antagonism

what is coagulation defects

decreases synthesis capability of the liver leading to decrease levels of most procoagulant factors as well as the natural anticoagulants, antithrombin and protein C , factor VII and von Willebrand factor tend to be elevated

what causes cirrhosis

mainly chronic alcohol consumption, then chronic viral hepatitis, metabolic liver disease, hemochromatosis, wilson’s disease, fatty liver, autoimmune hepatitis., and immunologic disease or drugs such as isoniazid, methyldopa, amiodarone, dronedarone, vitamin A methotrexate, tamoxifen didanosine and propylthiouracil

what pathway of alcohol consumption causes cirrhosis

CTP 2E1 which get upregulated in tolerance and produces the toxic species acetaldehyde and reactive oxygen species

what is general approaches to treat cirrhosis

stopping using what causes cirrhosis, if portal hypertension start propranolol or nadolol, if their is bleeding use octreotide, vasoconstrictors vasopressin, if
HTN furosemide or spironolactone, if hepatic encephalopathy use lactose to lower ammonia, to reduce GABA use flumazenil and bromocriptine for D2 antagonism

what are the types of IBS

IBS with constipation, IBS with diarrhea, Mixed IBS, and unsubtyped IBS

what should be used to stop diarrhea in IBS

loperamide is an opioid agonist, decreases muscle tone decreasing diarrhea,

what is hyoscine

muscarinic antagonist is an anti spasmotic used in IBS

what can be used as a laxative in IBS

lubiprostone is prostaglandin like increase chloride leading to increased water and motility, or linzess which increase transit and fluid, is a peptide mimic, increase guanylate cyclase C agonist

what is tenapanor

minimally absorbed sodium/hydrogen exchange inhibitor, leads to decrease sodium absorption increase the water content leading to increased intestinal transit rate

what is zelnorm, Lotronex and viberzi

zelnorm is a 5HT4 agonist and 5hT2B antagonist increases gastric motility, Lotronex is a 5ht3 antagonist, decrease moisture content and decrease gastric motility, and viberzi is a mixed mu and kappa opioid agonist delta antagonist stops diarrhea and decrease abdominal pain

what is constipation

decrease in bowel movement from baseline or increase strain to pass a bowel need to worry about impaction, bloating or blockage it is a symptom rather than a disease

what is fecal impaction

solid immobile bulk of stool in the recturm no medication can help need physical removal

what factors increase risk of constipation

more common in women, more common in patients with metabolic disease multiple medication, lock of exercise, inadequate fluid intake, and abuse of laxatives and pregnancy

where does most constipation occur and why

mainly occurs in the colon and can be due to colon cancer, benign strictures anal stricture or hemorrhoids or functional problems such as anal spams, IBS and aganglionosis, can be due to hypothyroidism, diabetes or hyperparathyroidism, parkinson disease or some psychological disorders

what medications are associated with constipation

opioids NSAIDs, anticholinergic ,antidepressants (TCAs), iron anti diarrhea agents and some antihypertensives

what is important to get in a history for constipation

duration of symptoms, associates symptoms, past medical history, new diet or new medications and physical exam

what are bulk forming agents

natural fibers not good to give if patient is currently constipated better at preventing future constipation events, should get soluble dietary fiber has increase gas/flatulence examples is psyllium, methylcellulose, and polycarbophil need to intake adequate water and do not work for opioid induce constipation and they need to be dispatched

what are emollient agents

useful for preventing constipation not treating really only useful to stop straining is benign

what is mineral oil

do not use

what are the sugar/not salt based osmotic laxative

bring water into the bowel. miralax is part of this class is the best lactulose is in this class it has increased glass miralax is 17 grams daily can do several times a day and do not really have to worry about side effects can use long term

what are the saline laxatives

electrolyte based laxatives that draw water into the colon, mainly magnesium have to worry about hypermag or any hyper electrolyte can not use in children or if CrCL below 30 should only be used as PRN and not long term examples are milk of mag and citrate of magnesium which is very effective

what are the stimulant laxatives

help stimulate peristaltic activity through local irritation of GI mucosa, Senna and Bisacodyl are examples

what are guanylate cyclase-C agonist

Liness and trulance stimulate cyclic GMP increase water release into colon CI in 2 or younger for linezz and 6 or younger for plecanatide normally second line due to cost

what is enema

very fast relief is not second line depends on patient preference

what is general treatment to constipation

reassurance and working with the patient to have good bowel habits such as a schedule, relieve stress and emotional disturbance, intake 10 grams daily of fiber, proper fluid intake and regular excercise and regular schedule

how is opioid induced constipation treated

senna or miralax can use methylnaltrexone or naloxegol (renal dosing at 60 CrCl) inhibit constipation from opioids

what is postoperative ileus

complication of surgery mainly with abdominal surgery decrease intestinal peristalsis or gastroparesis (reflux), causes symptoms of nausea vomiting abdominal pain and distension manage can use alvimopan which is ordered by surgery or prokinetic agents such as metoclopramide

why is lubiprostone not preferred

cause nausea and vomiting

what is important in Peds constipation

important to have a schedule bowel movements can use miralax

what are keytake aways of bowel preps

important to clear bowels do not want to do again, CI in ileus, suspected gastric retention, suspected or establish mechanical bowel obstruction, severe inflammatory or infectious colitis, unable to swallow, can be once but separated is better, for suprep need to take additional water on top of the bottle with medication

what is inflammatory diarrhea

typically has blood and mucus mainly is caused by infection but can be due to IBD r=or radiation enteritis

what is noninflammatory diarrhea

watery diarrhea from increased water secretion or decreased absorption mainly caused by viral infections

what makes diarrhea acute or chronic

acute is less than 14 days persistent, is 14-30 days and chronic is more than 30 days

how is water absorbed in the bowels

active transport energy is used to move substrate against is gradient is hove sodium is moved, diffusion is non energy sodium is also moved this way as well, and solvent drag a substance is dragged across a membrane water follow the solutes

what is villi cells

handle the absorption of solute and water use ATP to pump sodium into the body through a sodium potassium ATPase pump

what is a crypt cell

designed to secrete water and electrolytes from the enterocyte into the gut excrete chloride and water

what is osmotic diarrhea

is causes by water retention in the intestine due to poorly absorbed osmotically active agents in the gut, stops when patients are fasting, causes are laxatives, antacids containing mag, food containing sorbitol mannitol or xylitol or malabsorptive disease

what is secretory diarrhea

caused by reduced water reabsorption has increased secretion of electrolytes, persist through fast eating does not increase volume of stool is lacking leukocytes blood calprotectin or fat causes by senna Bisacodyl, antibiotics, metformin, cholinergic agents, colchicine, NSAIDS, and misoprostol, caused by staph and clostridium toxins and C. DIff