Gastrointestinal Physiology Objectives Answered

8/2/2019 Gastrointestinal Physiology Objectives Answered

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Gastrointestinal PhysiologySection 1Functions and Regulation of the GI Tract:

1. List the major organs within the GI system and overall functions of the GIsystem.- GI tract: mouth, esophagus, stomach, small intestine, large intestine, rectum

and anus

- Accessory glands: salivary glands, liver, gallbladder and pancreas2. Differentiate between ingestion, digestion, absorption, metabolism,

secretion, and excretion- Ingestion: take food into the body by swallowing or absorbing it.- Digestion: process of breaking down food by mechanical or enzymatic action in

the stomach and intestines- Absorption: pass into the body from the GI- Metabolism: chemical process occurring within a body to maintain life- Secretion: substances produces by cells or glands are moved into the GI- Excretion: removal from the body.

3. Review histological features of the wall

of the GI tract- Four histologically defined regions:

o Mucosa: consists of single layer

epithelium that is highly folded. Theepithelium is frequently invaginatedto form tubular exocrine glands

o Submucosa: connective tissue layer

with major blood and lymph vessels.Also has large number of ganglioncells forming the Meissners plexus

o Muscularis externa: contains major

smooth muscle (peristalsis); innercircular and outer longitudinal

o Serosa: thin connective tissue through which the major vessels and

extrinsic nerve enter4. Compare and contrast smooth and striated muscle with respect to

structure, excitation contraction coupling, and cellular mechanism ofcontraction.Comparison between Smooth and Straited Muscles.- Cell bundles in SM have diverse orientations due to the lack of a discrete

muscle origin and insertion.- Contractile filaments are arranged irregularly (no sarcomeres) this allows

force generation over a wide range of muscle lengths (termed lengthadaptation). There are large numbers of actin filaments attached to densebodies and it is mainly through interconnections of these dense bodies that theforce of contraction is transmitted from cell to cell.

- Smooth muscle contains both actin and myosin filaments. It does not containthe normal troponin complex that is necessary in the control of skeletal musclecontraction.

- Contraction of smooth muscle requires conformational alteration of myosinhead whereas with striated muscle there is movement of the troponin-tropomyosin complex on the actin filament.


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- The Sarcoplasmic Reticulum is not organized into a T-tubule system. Thecaveoli which represent invaginations of the smooth muscle membrane areanalogous to T tubules in striated muscle

- Smooth muscle can contract for long periods at low levels of energyconsumption and low myosin cross bridge recycling rates.

Contraction:- Smooth muscle activity is controlled by nerves, circulating hormones, by

stretch of the muscle and other tissue factors.- In both calcium is key to contraction, when cellular level is high enoughcontractile protein interact. When extracellular Ca2+ enters it can trigger therelease of Ca2+ from internal sources.

- Once calcium binds to calmodulin they both activate MLCK whichphosphorylates myosin which interacts with actin causing contraction.

5. Review histological features oftransporting epithelia.- Leaky epithelium: low resistance,

cant build large potential difference.Seen in proximal renal tubule, smallintestine, gallbladder, and choroidplexus. They have high waterpermeability

- Tight epithelium: high electrical

resistance, do build up significanttransepithelial potential differences.Generally these are not important intransport

6. Provide general cellular models offluid absorption and secretion.Absorption = movement of substances into the blood stream. An example is aNa+ channel in tight epithelia, but can also be Na+/H+ exchange or a Na+cotransporter. Absorption is characterized by passive Na+ entry at the apicalmembrane and active Na+ extrusion at the basolateral membrane. In tight


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epithelia the movement of Na+ through apical membrane channels create a flowof positive charge from the lumen to the interstitium that induces a lumen-negative transepithelial potential difference. This is the driving force for passiveCl- absorption across the tight junction. (paracellular) vs Na+ was transcellular

Secretion = movement of substance out of the blood. Transport is not the simplereverse of absorption. It centers on Cl- movement, rather than Na+. The

electrochemical gradient for Na+ is still of key importance to drive secondaryactive Cl- uptake at the basolateral membrane. This results in an intracellular Cl-activity above electrochemical equilibrium. Secretion is initiated by opening Cl-channels in the apical cell membrane. The resulting Cl- current provides Cl- fluxand also generates a lumen negative transepithelial potential difference, whichdrives passive paracellular Na+ secretion.

*Clinical: Cystic Fibrosis notable failure of airway and pancreatic duct secretoryepithelia, due to loss of the apical membrane Cl- channel = thick mucus,obstruction

7. Describe neural, endocrine, and paracrine modes of control and giveexamples of each.

CCK an example of endocrine controlo Enteroendocrine cells have apical microvilli which have receptors that

taste the gut lumen. I-cells (CCK secreting) detect long-chain fattyacids and products of protein digestion which results in the release ofhormone from granules located at the basal part of the cell.Hormones are secreted by exocytosis and enter the blood capillariessupplying the intestinal mucosa. GI hormones then pass through the

liver via the hepatic portal vein, then into the systemic circulation.


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Serotonin, somatostatin, and histamine examples of paracrine controlo Serotonin is present in large quantities w/i enterochromaffin (EC) cells.

In response to mechanical stimulation of the gut wall EC cells releaseserotonin. Its effects are generally excitatory, resulting in increasedintestinal motility and secretion. Serotonin exerts its effects largelythrough interactions with the ENS.

o Somatostatin peptide produced by D-cells. It may be released into

the blood and act as a hormone, or a paracrine mediator. It is potentinhibitor it inhibits pancreatic secretion, gastric secretion andmotility, gallbladder concentration and nutrient absorption.Somatostatin is also a vasoconstrictor (used to treat GI hemorrhage).

o Histamine present in mast cells and enterochromaffin-like cells (ECL)

in the stomach mucosa. Local release of histamine in stomach is

important for stimulatory effects on gastric acid secretion. In theevent of local infection or injury, mast cell degranulation may occurresulting in vascular effects including local edema and vasodilation.

For neural example see #8

8. Describe the intrinsic and extrinsic innervations of the GI tract.The intrinsic innervation of the GI tract is through the enteric nervous system(ENS). The ENS is a mini-brain and initiates patterns of the GI activity byfunctioning autonomously without extrinsic activity. It is arranged anatomicallyinto nerve networks in the myenteric and submucosal plexuses. The myentericplexus is primarily involved with control of motility and innervates the longitudinal

and circular smooth muscle layers. The submucosal plexus mainly innervates theglandular epithelium, intestinal endocrine cells, and submucosal blood vessels tocontrol intestinal secretion. The ENS uses Ach, amines (serotonin), purines (ATP),gases (NO), and peptides (GUT-BRAIN peptides).


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The extrinsic innervation of the GI tract The Gut-Brain axis although the ENS iscapable of independent activity, it is modulated by the CNS. Anatomicalconnections between the ENS and CNS are via extrinsic nerves from theparasympathetic and sympathetic divisions of the ANS. The flow of info is bi-directional between the CNS and GI tract, giving rise to the concept of a gut-brainaxis.

PSNS efferent nerve stimulation (mostly from vagus n) generally causesexcitation. Most fibers exert their effect by ending on ganglia w/i the ENStherefore give command signals to ENS. The vagus n. is particularlyimportant in control of the upper GI tract (esophagus, stomach, duodenum,gallbladder, and pancreas). PSNS outflow to secretory epithelial cells isuniversally excitatory. PSNS to gut smooth muscle has parallel inhibitoryand excitatory fibers. Excitatory neurotransmitters = Ach and substance P;inhibitory neurotransmitters = NO and ATP. VIP is inhibitory to SM butexcitatory to secretory enterocytes. PSNS also contains sensory afferentfibers from the GI tract that transmit sensations such as non-painfuldistension and nausea.

SNS generally acts to antagonize parasympathetic excitatory effects, withNE acting on alpha2-presynaptic receptors to inhibit Ach release byparasympathetic nerves. Other efferent sympathetic fibers mediatevasoconstriction to reduce intestinal blood flow. SNS also convey sensoryafferents from the GI wall to the CNS, conveying sensations of pain andnausea.

9. Name the major GI hormones and the location of the endocrine cells thatsecrete them. Describe the main stimuli for secretion of each hormoneand their main physiological actions.

Name Loc of endocrinecells that secretethem

Main stimuli forsecretion Physiologicalactions

Gastrin G-cells of gastricantrum

amino acids,distension ofstomach by food,vagus nerve activityvia GRP-inhibited by H+ inthe lumen of the

-Incr secretory activity ofstomach-trophic (growthpromoting effect) onstomach mucosa


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stomach and bysomatostatin

Cholecystokinin

I-cells of duodenumand jejunum

Fatty acids,monoglycerides,small peptides andamino acids

-contraction ofgallbladder andrelaxation of sphincter ofoddi-stimulates pancreaticenzyme secretion

-potentiates secretin-induced pancreaticbicarb secretion-stimulates growth of theexocrine pancreas-inhibits gastricemptying

Secretin S cells of duodenum Acid and amino acid -incr bicarbonatesecretion by pancreasand biliary system,thereby neutralizing aciddelivered to theduodenum and stomach-this allows digestiveenzymes in the SI tooperate at optim pH-inhibits acid productionby stomach

Ghrelin X-cell, secreted frombody of stomach

Hypoglycemia andlow body weight

-potenet stimulator offood intake and growthhormone release-secretion is highest inthe interdigestive period

Motilin M-cell in distalstomach and small

instestine

An ill-defined clockexists within the

ENS that determinesthe interval btwmeals and promptsmotilin secretionwhen appropriate

-stimulates a pattern ofcontraction seen in thedistal stomach and SIbtw meals (MMC migrating motorcomplex)-acts on neurons withinthe ENS to being theMMC contractions

GIP (Glucose-dependentInsulinotropicPolypeptide)

Small intestine Secreted inresponse to fat andglucose in the smallintestine

-when given in largedoses causes inhibitionof motor and secretoryactivity in the stomach-in smaller doses itpromotes the secretionof insulin

Glucagon-likePeptide-1(GLP-1)

L-cells of the gutmucosa of SI

Secreted inresponse to glucosein the SI lumen

-promotes insulinsecretion and inhibitsglucagon secretion bypancreatic islet cells.

10. Explain what is meant by Cephalic, Gastric, and Intestinal phases ofthe GI tract regulation.The integrated response to a meal causes three phases of gastric secretion cephalic, gastric, and intestinal phases. Cephalic phase describes the results ofanticipation, sight, smell, and taste of food. Gastric and intestinal phases refer to


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events occurring as a result of food being present in the stomach and intestines,respectively.

Section 2Mouth, Salivary Glands, and Esophagus:

1. Describe functions of chewing.- Reduces particle size of food and increased exposure to saliva.- Lubricates food for swallowing and aids carb digestion via salivary amylase.- Taste receptors stimulated

2. Outline functions of saliva.- 70% produced by submandibular glands, 25% from parotid glands, and 5%

from sublingual glands.- Maintains oral pH of 7 at rest- When stimulated the glands produce a slightly alkaline fluid- Functions: lubrication (moisten, mucins), protection, (lysozyme, lactoferrin, IgA)

and digestion (alpha-amylase, lingual lipase)

3. State which digestive enzymes are present in saliva, their substrates anddigestion products.- Alpha-amylase: starch- Lingual lipase: fats

4. Describe electrolyte composition of saliva and how it changes with flowrate. Explain salivary flow rate curves based on transport properties ofthe acinus and striated ducts.- Primary secretion formed by acini is isotonic and has a composition close to

plasma- At low flow rates the saliva is hypotonic, at high flow rates it has an osmolality

approaching that of plasma

- Contraction of myoepithelial cells helps to move fluid out of the blind-endedacini into the striated ducts via the intercalated duct.

o Striated duct: reabsorbs NaCl

o Ducts have low permeability, this is what cuases the saliva to become

hypotonic- Flow rate curves come about due to the length of time the duct has to modify

the primary


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5. Outline control mechanisms for production of saliva- Autonomic system is the sole mechanism of

control, parasympathetic is the mostimportant

- parasympathetic outflow is viaglossopharyngeal and facial nerves

- direct innervation of local blood vessels by

parasympathetic nerves causes vasodilatationby local release of vasodilator metabolites andkallikrein

o causes glands to grow

- only hormonal effect on saliva secretion isincreased ductal Na+ absorption and K+

secretion in response to aldosterone.

6. Describe swallowing sequence and identify voluntary and involuntarycomponents.- Voluntary stage: where food is shaped into a bolus, collected on the tongue and

pushed into the pharynx. The tongue is raised against the hard palate to createthe pressure gradient that forces the food into the pharynx and beyond.- Involuntary stage: once food enters the pharynx, the nasopharnyx is closed by

the soft palate and contraction of the superior pharyngeal constrictor. Closureof glottis, elevation and forward displacement of the larynx and deflection ofthe food bolus by the epiglottis, together prevent food entering the airway. TheUES relaxes to allow the bolus to enter the esophagus. Breathing is stoppedduring these steps.

- Swallowing is coordinated by a center in the reticular formation. The oral andpharyngeal component of swallowing is controlled solely by extrinsic nerves,neurologic damage can adversely affect this phase of swallowing.

7. Identify the normal resting esophageal pressure and explain why itvaries with the respiratory cycle.Normal esophageal pressure is: UES = +40 mmHg, mid-esophagus = -5 mmHg,LES = +20 mmHg, stomach = +5 mmHg.

8. Describe the origin and consequence of the high basal tone found in theupper and lower esophageal sphincter.

9. Contrast anatomical and functional characteristics of the upper, middle,and lower parts of the esophagus.The esophagus can be divided anatomically into an upper third surrounded bystriated muscle and a lower two thirds consisting of smooth muscle.

Physiologically, the esophagus has 3 functional zones. The upper zone is closelyrelated to the pharyngeal musculature and consists of striated muscle. Themiddle zone consists of smooth muscle and the lower zone constitutes the loweresophageal sphincter.


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10. Compare and contrast primary and secondary esophagealperistalsis.Swallowing induces a wave of peristalsis known as primary peristalsis. If this isinsufficient to move a bolus all the way to the stomach, distension of theesophageal wall by a remaining bolus induces a secondary peristalsis, which isrepeated until the bolus enters the stomach.

11. Contrast motility defects in the lower esophageal sphincter that isresponsible for heartburn and achalasia.Acid reflux: Acid reflux from the stomach occurs physiologically. The problem iswhen the LES is not working properly. Acid in the esophagus is neutralized bysaliva and also induces secondary peristalsis to rapidly return to the stomach. IfLES function is diminished and reflux occurs chronically, a patient has Gastro-Esophageal Reflux Disease (GERD). Symptoms include pyrosis (heartburn) andmucosal damage.Achalasia: (absence of relaxation) is a disorder with its origin in the ENS,affecting esophageal smooth muscle. There is a loss of peristalsis and a failure ofthe LES to relax properly. Patients have great difficulty swallowing, frequentlyaspirate food, and suffer malnourishment.

Section 3The Stomach

1. Describe the motor patterns of the stomach following ingestion of ameal.


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1 Fasted state2 Receptive relaxation & accommodation ingestion of meal requires proximalstomach to relax so relaxation and accommodation occur to allow food to enterthe stomach and store it without causing a rise in intragastric pressure mediatedby vago-vagal reflexes.3 Peristalsis begins once food is ingested, proximal stomach exhibits slowsustained contractions that gradually press food into the distal stomach. Tonic

contraction of the proximal stomach determines intra-gastric pressure, which isthe main determinant of the gastric emptying of liquids.4 Retropulsion contractions of the distal stomach serve to grind food(trituration) and to mix it with gastric juice. The powerful contractile waves seenat this time = antral systole and food is broken down by retropulsion in whichfood is forcefully reflected back from the pyloric sphincter into the stomach.

2. List the endocrine and exocrine secretions of the stomach, their cells oforigin, and their functions.

Name Cells of origin Functions

Exocrine Secretions

HCl

Gastric mucosa

-Denatures proteins,helping digestion-Cleaves pepsinogens

Pepsinogen

-Proenzymes that arecleaved to produceactive proteolyticpepsins

Mucus

-Lubricates ingestedsolids, helping gastricmotility-Forms part of gastricmucosal barrier againstacid and pepsin attack

Bicarbonate-Forms part of thegastric mucosal barrier

Intrinsic Factor

-Forms complex with vit

B12 in small intestine-Needed for vit B12absorption in ileum

Gastric Lipase-Contributes totriglyceride hydrolysis

Water-Dilute and dissolveingested food

EndocrineSecretions

GastrinAntrum

Stimulates acidproduction

Somatostatin Inhibits acid production

3. Contrast the electrolyte composition of gastric juice with plasma and

explain how this relationship changes with secretory rate.The composition of gastric juices changes with secretion rate. At all rates it isapproximately isotonic with plasma. At low flow rates it resembles interstitialfulid while at high rates is becomes a solution primarily of HCl. This change isexplained by the two component model. At rest, the gastric juice compromises anon-oxyntic component derived from paracellular diffusion of interstitial fluid andsecretions of mucus cells. This produces a basal alkaline fluid of constantcomposition and low volume. As oxyntic cells are stimulated the non-oxyntic fluidis gradually diluted with HCl/KCl until the final [Na+] is only about 5mM. Pureoxyntic fluid is slightly hyperosmotic. This model is important since patients


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suffering from prolonged vomiting, or nasogastric suction, may lose large amountsof gastric juice.

4. Provide a model explaining the cellular basis of gastric acid secretionand the generation of the alkaline tide.The alkaline tide refers to a condition, normally encountered after eating a meal,when stomach acid is released into the stomach causing a temporary increase inpH of the blood. The active transporter H+/K+ ATPase is used to pump the H+ outof the cell up an immense concentration gradient. K+ secretion via luminalmembrane K+ channel provides the K+ needed by the H+/K+ ATPase to pump H+out of the cell. OH- inside the cell produced along with H+ is neutralized bycombining it with CO2 to form bicarbonate. Most of the CO2 comes from oxynticcell metabolism. The HCO3 produced leaves the cell in such quantity that thegastric venous plasma becomes alkaline = post-prandial alkaline tide. Cl-enters the cell against in concentration gradient by coupling its entry with the exitof HCO3. Secretion of Cl- via a channel results in the formation of a large negativeelectrical potential in the stomach lumen. This is important to reduce the overallelectrochemical gradient up which H+ needs to be transported. It can be thoughtof as trapping H+ in the lumen and thus contributes to the barrier functionagainst acid self-attack of the mucosa.

5. Explain how gastric secretion is stimulated during the interdigestive,cephalic, gastric and intestinal phases.

- Interdigestive: gastric secretions continues at about 15% of maximalproducing, the characteristic low pH of the stomach contents at rest.

- Cephalic: mediated by the vagus nerve. The thought of a meal is sufficientto increase acid production. Afferent signals pass up the vagus nerve to the

vagal nucleus and down the efferent vagal fibers to the stomach. There aretwo ways that gastric acid secretion is stimulated during this phase:o release of Ach by nerve terminals on oxyntic cells

o post-ganglionic vagal efferents ending on G-cells release GRP causing

gastrin release.Note that during this phase gastrin secretion is suppressed whenintragastric pH is below 3.- Gastric: acid secretion during this phase accounts for 50% of theresponse to a meal. When food enters the stomach there is a rise in pH toabout 6, this causes more gastrin secretion to occur. Distension of the
http://en.wikipedia.org/wiki/Stomach_acidhttp://en.wikipedia.org/wiki/PHhttp://en.wikipedia.org/wiki/Stomach_acidhttp://en.wikipedia.org/wiki/PH


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stomach is also a key stimulus during the gastric phase as it activates thevago-vagal reflex and the ENS. Long loop vago-vagal reflexes operate,where the efferent pathway is very similar to that described for the cephalicphase. Short reflexes within the ENS also support the same activationmechanisms, since cutting the vagus does not abolish neurally mediatedacid production.- Intestinal: partially digested peptides and amino acids in the proximal

part of the small intestine activate the duodenal G cells to produce gastrin.5-10% of the total gastric secretion comes from this phase.6. Describe negative feed back mechanisms that inhibit secretion of gastric

acid.- 1 hour after ingestion of a meal, gastric acid secretion is at max and most of

the meal has entered the small intestine.- Once the pH falls below three the G cells are inhibited by H+ concentration.- Lowered pH also activates D cells to release somatostatin which inhibits

gastrin release.- Lowered pH also directly inhibits oxyntic cells.- The presence of acid, fatty acids, and hyperosmotic

fluids in the small intestine all stimulate the releaseof hormones from endocrine cells that inhibit gastricfunction called enterogastrins.

o secretin is the main one.

o GIP: released in response to glucose and fatty

acids and can inhibit oxyntic cellso CCK: released in response to protein and fat

digestion products and reduces motility ratherthan acid production.

7. Describe how pepsinogen secretion is controlled and what factors areimportant for its conversion to pepsin.Pepsinogens are proenzymes that are cleaved and activated when pH drops below5. The pepsin produced then autocatalyses conversion of pepsinogen to pepsin.

8. Explain what is meant by the gastric mucosal barrier and indicate themain agents known to disrupt it.This is one layer involved in the protecting the mucosa from erosion. It is effective

at neutralizing acid due to the bicarbonate that gets trapped in the mucus gel.Note that the tight junctions are the most important factor preventing backdiffusion of H+.


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Certain agents can disrupt this barrier including ethanol, bile salts orasprin/indomethacin. Disruption can be associated with gastritis and after time,ulcers.

Pancreas and Biliary System:

9. Explain what primary and secondary bile acids/salts are and indicatetheir relative abundance in human bile.Hepatocytes synthesize and secrete the primary bile acids, cholic acid andchenodeoxycholic acid. Most of these bile salts are conjugated to glycine ortaurine to produce glycocholate and taurocholate, respectively. This conjugationmakes them more soluble. Primary bile salts undergo bacterial modifications inthe gut lumen. 10-20% undergo deconjugation and are reabsorbed in the smallintestine and reconjugated in the liver to be secreted again.

During this process dehydroxylation may occur to create secondary bile acids

(cholic deoxycholic acid; chenodeoxycholic acid lithocholic acid).

10. Outline mechanism of the bile acid secretion by hepatocytes.95% of the bile acids arriving in the intestine are reabsorbed (via Na+-bile acidcotransporter), these acids return to the liver-via the portal vein. Bile acids thatbecome deconjugated are largely unionized and reabsorbed by simple diffusion inthe jejunum due to their higher lipid permeability.Typically, around 0.2g of bile acids is excreted in feces each day. This is replacedby new synthesis of primary bile acids by the liver. The rate limiting step insecretion of bile acid is the transport across the canalicular membrane viafacilitated diffusion.

11. Explain what is meant by the amphipathic properties of bile acidsand predict how this property assists the digestion of fats. Contrast thephysical state of emulsion with a micellular solution.Bile acids are amphipathic which means a portion is polar and a portion is non-polar. The polar outer shell interacts with water and the hydrophobic inner regioninteracts with insoluble fatty acids, and cholesterol.


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In mixed micelles the other amphipathic molecules (phospholipids andmonoglycerides) line up with their polar heads facing outwards and their tailsfacing the hydrophobic code. The mixed micelle is more efficient at dissolvingother hydrophobic molecules. Thus, micellesare in a true solution unlike emulsions.

12. Define the enterohepatic circulation

of bile acids.The total bile acid pool is about 3.5g which isnot enough to assimilate the lipid content of atypical meal, Therefore, bile acids arerecycled, with the total bile acid pool secretedapproximately twice during each meal andaround 6-8 times a day. This is achieved byenterohepatic circulation of bile acids.

13. Discuss factors which govern the rate of bile flow and the rate ofsynthesis of new bile acids. Outline the effects of CCK and secretin onsecretion and delivery of bile to the duodenumRegulation of bile acid synthesis in hepatocytes is mainly governed by theirdelivery from the intestine via portal blood. High delivery rates in sinusoidal bloodcauses stimulation of bile fluid secretion, but also inhibits synthesis of new bileacids.

14. Outline the functions of the gallbladder and the control of

gallbladder motility.During the interdigestive phase the tone of the sphincter of Oddi is increased andthe wall of the gallbladder is relaxed this promotes flow of hepatic bile into thegallbladder. More than 50% of the hepatic bile flow enters the gallbladder duringthe interdigestive period.Between meals bile is secreted constantly and the volume produced can greatlyexceed the small volume of the gallbladder. This difference is accounted for by theNaCl and water reabsorption by epithelial cells lining the gallbladder.During a meal the bile flow rate is at its highest. The cephalic phase causesgradual contraction of the gallbladder which is mediated by cholinergic vagalnerves. Once the meal is in the intestine a powerful signal for gallbladder

contration comes from CCK release. CCK also relaxes the sphincter of Oddi, whichis the key event that allows pancreatic and biliary secretion to enter theduodenum and digest the meal.*****

15. Describe the processes of bile pigment synthesis, modification ofsecretion. Predict changes in plasma bile pigment concentrations injaundice with pre-hepatic and post-hepatic causes.About 2% of biliary solids are bile pigments. The major pigment is bilirubin whichis derived form the breakdown of hemoglobin in macrophages by hemeoxygenase. Bilirubin is insoluble and is therefore transported bound to albumin.


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The liver takes up free bilirubin and transports it to the endoplasmic reticulumwhere it is conjugated with glucuronide via glucuronyl transferase. This is calledconjugated bilirubin and is water soluble it can now be transported across thecanilicular membrane. Half of this is delivered to the intestine and excretedunaltered. Intestinal bacteria is reabsorbed and returned to the liver in the portalvein. Much of the urobilinogen is processed again by the liver and delivered to theGI tract. In the colon the urobilinogen is metablized by bacteria into stercobilin.

Some of the urobilinogen escapes hepatic uptake and enter systemic circulation.At the kidneys this is filtered into the urine and oxidized to urobilin. Below is apictorial representation.

Small Intestine:1. Describe segmenting and peristalic patterns of motility seen in the small

intestine during the fed state and indicate their function.- Segmenting: contractions are often regular, producing a string of evenly sized

segments, but can also be irregular or even isolated. They can also vary instrength. Segmentation is effective at mixing lumenal contents

- Peristalsis is a reflex event in which a ring of contraction moves a bolusaborally. The major stimulus for peristalsis is mild/moderate distension of thegut wall.

o Requires carefully timed sequence of contractions in the longitudinal and

circular muscle layers.o

Contracting segment: the circular muscle contracts, forcing the bolusforward. At this time the longitudinal muscle relaxes in this area, and thecircular muscle in the immediate downstream area relaxes (known asreceptive receptive relaxation).

o Receving segment: longitudinal muscle layer contracts to pull the bowel

wall over the bolus like a sleeve.2. Describe the changes in osmolarity that occur in chyme as it passes form

the stomach and along the small intestine.- Chyme: Semifluid material produced by the gastric digestion of food.

Results partly from the conversion of large solid particles into smaller


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particles through peristalsis and the contraction of the pyloric sphincter.- Fluid absorption in the small intestine is isosmotic and not subject to

hormonal regulation- If food is present in the upper small intestine, high epithelial water

permeability ensures rapid osmotic equilibrium with plasma. After this,absorption of fluid depends on active transport of nutrients and electrolytes.

- Na+ is taken up at the luminal membrane driven by low intracellular

concentration of Na+. There is extrusion at the basolateral surface by theNa+ pump.- Fluids absorbed after a meal are generally a result of sodium and nutrient

uptake- These features of the intestine indicate that the osmolarity of the chyme is

not changed until it reaches the colon where it is concentrated- Bicarbonate in intestinal secretions protects intestinal mucosa by

neutralizing any H+ present in lumen important in duodenum and jejunumwhere bacteria produce acids from degradation of certain foods

3. Relate pathways by which sodium, water, iron and calcium are absorbed

in the small intestine.Sodium nutrient coupled sodium absorption, Chloride-coupled, Na+/H+exchangeWater - absorbed as a result of sodium and nutrient uptake.Iron - Mostly arrives at intestine as heme, but some as ferric/ferrous iron. Divalentcation transport brings the ferrous form of iron into duodenal enterocytes. Hemehas its own transport, and is then split to ferric iron using heme oxygenase. Thereis also a process where the cell secretes a transferring that binds the iron andbrings it into the cell.Calcium - In duodenum/jejunum Vitamin D3 increases intestinal Ca2+ uptake byinducing synthesis of transport proteins. Calcium enters the cell down a steepelectrochemical gradient via a Ca2+ channel

4. Describe the process of intestinal fluid secretion, indicating itsphysiological function and its importance in secretory diarrhea.Secretory diarrhea is caused by an increase in active secretion or inhibition ofabsorption.Bacterial enterotoxins activate mechanisms that cause the intestinal fluidsecretion and ultinately result in secretory diarrhea. The enterotoxins incraesecAMP which opens Cl- channels, they also increase calcium which opens calciumgated Cl- channels. Chloride leaves the intestinal cells into the lumen causing Na+

to follow paracellularly. Since water follows throuh osmosis, diarrhea results.

5. List the chemical classes of carbohydrate, protein and fat entering theduodenum from the stomach, and identify mechanisms mediating furtherdigestion. Indluce pancreatic secretions and brush border enzymes.Carbohydrates:

- Duodenum: Salivary amylase begins the processof digestion in the mouth, but carbohydrates of alltypes enter the duodenum(mono,poly,oligosaccharides)

- Pancreatic Secretions: Pancreatic amylasecontinues the digestion of remaining


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carbohydrates- Brush Border Enzymes: Brush border enzymes also digest disaccharides and

oligosaccharides- Carbs must be broken into a monosaccharide form in order to be absorbed

by the intestines

Protein:

- Duodenum: Pepsin begins digestion in stomach, proteins only partiallydigested- Pancreatic Secretions: Pancreatic enzymes act on the partially digested

proteins:o elastase

o chymotrypsin

o trypsin =endopeptidases, they hydrolyze internal peptide bonds

o Resulting oligopeptides are then attacked by ectopeptidases which

remove one amino acid at a timeo Carboxypeptidase A works on products of chymotrypsin, elastase

o Carboxypeptidase B acts on products of trypsin digestion

- Brush Border Enzymes: Aminooligopeptidase is the major proteolytic brushborder enzyme

Fat:- General: Triglycerides, lecithins/PL, sphingolipids, sterols, fat-soluble

vitamins (A,D,E,K)o Chewing and grinding peristalsis break fat droplets into smaller

pieces, helping to create an emulsiono lingual lipase, gastric lipase

o (people with pancreatic insufficiency can partially digest)

- Pancreatic Secretions:o Pancreatic lipase: an alkaline lipase, produces monoglyceride and

releases two FFAs from parent TG molecule.o Products enter a micelle because they are insoluble.

o Other enzymes: phospholipase A, carboxyl ester lipase

- Brush Border Enzymes: Micelles coming close to the brush border release FAand monoglycerol which is taken up by the enterocytes. There is no enzymeaction at this location

6. Describe mucosal barrier across which absorption takes place.A layer of poorly stirred fluid (the unstirred water layer) coats the surface of theinstestinal villi). This layer reduces the absorption of the lipid digestion productsbecause they are poorly soluble in water. Thisregion is usually acidic.

Large Intestine:1. Identify substrates and products of colonic

bacterial metabolism and predict theimpact on the rate and composition ofintestinal gas formation.The main bulking agent in stools are the non-starch


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taken up by cells through the Cl-/HCO3- pump. This causes a large depletion ofbicarbonate and the hydrogen builds up inside the cells causing metabolicacidosis.

Enteric Motility:

1. Divide the GI tract into functional segments based on the location ofsphincters. Review patters of motility that occur along the GI tract in thefed state.

Sphincter Segments SeparatedUpper esophageal sphincter Mouth/pharynxLower esophageal sphincter Esophagus/stomach

Sphincter of Oddi Common bile duct/ duodenumPyloric Sphincter Stomach/duodenum

Ileocecal sphincter Ileum/cecumAnal Rectum/external environment

The patterns of motility that occur along the GI tract are propulsion, mixing, and

reservoirs. These are explained in earlier objectives2. Describe the basic electrical rhythm (BER) of each region of the GI tract.

Explain the role of Intestinal Cells of Cajal in the origin and propagationof the BER. Correlate the BER with motility patterns.In the smooth muscle cells of the G.I there are slow undulating changes in restingmembrane potential known as BER. These are generator potentials, whichthemselves rarely cause muscle contraction. Only when threshold of 40mV isreached will contraction occur. Contractions are associated with spike potentialsand only occur at the peak of a slow wave. Therefore the maximum possiblefrequency of contraction is set by the rate of slow wave generation.The smooth muscle cells have no pacemaker activity of their own, the origin of

oscillations in their membrane potential is the Interstitial Cells of Cajal (ICCs).These fibroblast-like cells are positioned between the longitudinal and circularsmooth muscles and are closely associated with the myenteric plexus. The ICCshave multiple processes which are electrically coupled to the smooth muscle cells.

3. Describe the sequence of events occurring during reflexive defecation,differentiating those movements under voluntary control and thoseunder intrinsic control.

When the rectum becomes sufficientlydistended by fecal matter, therectosphinteric reflex is initiated which

causes internal sphincter to relax(intrinsic control). This event isassociated with an urge to defecate.Through voluntary contraction of theexternal anal sphincter a person is ableto override this reflex. The internalsphincter regains tone and rectalstretch receptors are able toaccommodate the distention. Rectalwall relaxes and pressure returns to


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normal.When more material enters the rectum following mass movements of the colonthe process repeats. When the person finally gets to a toilet the completedefecation reflex occurs. Both the internal and external sphincters relax. Theperson voluntarily strains to raise intraabdominal pressure and relax the pelvicfloor. This is in conjunction with propulsive involuntary contraction of the leftcolon and rectum.

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Gastrointestinal Physiology Objectives Answered