Gastrointestinal Physiology Overview The GIT is a long muscular tube of 5m with a set of accessory organs. General Function of the GIT: 1) Supplying nutrients to the body for bodily functions. 2) Homeostasis of energy (30kcal/kg/day) and fluid and salt. 3) Integration with other system Hepatobiliary Cardiovascular with respiratory Renal 4) Defence from the exposure to external environments. Nutritive Function of the GIT: The digestive system is responsible for: Ingestion Digestion Absorption Defecation Before the food can be used by body, it must be processed. This involves: Motility Secretion Membrane transport Motility Esophagus Transport food from mouth to stomach Prevent retrograde movement of esophagel or gastric contents A hollow tube (25-30 cm) closed at both ends by: o Upper esophageal sphincter (UES) Controlled by swallowing centre
Transcript
Gastrointestinal PhysiologyOverviewThe GIT is a long muscular tube of 5m with a set of accessory organs.
General Function of the GIT:1) Supplying nutrients to the body for bodily functions.2) Homeostasis of energy (30kcal/kg/day) and fluid and salt.3) Integration with other system
Hepatobiliary Cardiovascular with respiratory Renal
4) Defence from the exposure to external environments.
Nutritive Function of the GIT:The digestive system is responsible for:
Ingestion Digestion Absorption Defecation
Before the food can be used by body, it must be processed. This involves:
Motility Secretion Membrane transport
Motility
Esophagus Transport food from mouth to stomach Prevent retrograde movement of esophagel or gastric
contents A hollow tube (25-30 cm) closed at both ends by:
o Upper esophageal sphincter (UES) Controlled by swallowing centre
o Lower esophageal sphincter (LES) Cardiac sphincter Modulated by swallowing centre
o Other than the sphincters, the rest of the tube is smooth muscles Complicated by the airways cross in the pharynx hence, requires precise control
and coordination of swallowing and respiration
o When in doubt, everything goes to the stomach. Hence babies need to burp after eating as air enters the stomach too.
Gastric contents are damaging to esophageal epithelium Must prevent reflux, except vomiting or belching Tonic contraction (always contracted) in UES and LES prevents or minimizes
gastro-esophageal reflux or regurgitation. Increase tone by: cholinergic agonist, aplha-adrenergic agonist, gastrin,
substance P Decrease tone by: Beta-adrenergic agonist, dopamine, CCK, nicotine, tea,
coffee, cola
Stomach (Gastric Motility)
FunctionDuring interdigestive period
Clear undigested debris and sloughed epithelial cells After a meal
Relaxes to accommodate ingested food with little change in intra-gastric pressure (maintain the pressure at proximal end so that food will enter)
Grinds and disperses the meal into fine particles at distal endo However, we should not depend on stomach for grinding (still have to
chew!) or else will develop stomach ulcerThe contents are delivered to duodenum at a rate that affords (feedback relaxation):
Optimal mixing with pancreatic-biliary secretions Maximal contact with the brush border of enterocytes (for absorption)
Receptive Relaxation (to accept the food) Reduction in proximal gastric tone with the act of swallowing
Occurs with a dry swallow or mechanical stimulation of pharynx or esophagus Relaxation occurs within 10 s of swallowing (time taken for food to travel from
mouth to stomach) Allows stomach to accept a volume load without a significant rise in gastric
pressureReflex relaxation in response to gastric distension
Mediated by mechanoreceptors in the gastric wall
Gastric Accommodation (Adaptive relaxation)Does not require stimulation of pharynx or esophagus
Maintain a stable intra-gastric pressure Very effective Modulates gastric tone in response to the specific properties of the meal.
Mediated by vagovagal (involving vagus nerve) reflex arc and volume Truncal or proximal gastric vagotomy (removing the vagus nerve) decrease
gastric distensibility o Increased intra-gastric pressure after ingestion of meal, hence have to
eat small meals more frequently
Muscles stores glycogen and uses E from the conversion of glycogen to glucose. It does not touch the blood glucose (meant for brain).
Pyloric SpincterRegulates the gastric emptying and prevents duodenal-gastric reflux. It is the "antroduodenal unit". Emptying of gastric is in relation to the food.
Regulation of Gastric Emptying Influenced by:
o Gastro-gastric, duodeno-gastric, entero-gastric (decrease motility) reflexes
o Neural control (stress effects, nausea)o Hormonal control (Cholecystokinin (CCK), Glucagon Like Peptide-1
(GLP-1), Peptide YY)o Volume, composition & physical state of gastric contents
The rate is slower for: o Solid meal: due to small sphincter opening o Low volume meal: as the change in pressure is not large enough,
hence the food does not travel to duodenum o Fat: inhibit gastric emptying
Most potent o Proteins: need a lot of time to ensure there’s no wastage o Chyme with high acidity or high osmotic pressure: requires longer time
for duodenum to process
Liquid: Water or isotonic saline empty rapidly.
T½ ranging from 8 to 18 min First-order kinetics
o 300-ml bolus of saline empty 2x faster than 150-ml load (by volume)
Nutrients delay gastric emptying Feedback from small intestine alters the first-order
kinetics o 300ml 11% glucose empty as fast as 150ml 11% glucose
Higher the caloric density (energy densiy), slower the emptying o Maximum inhibition with 1 M (18%) glucose (held in stomach longer if
beyond) CH2O and most amino acids act on small intestine osmoreceptors
o Fructose is less potent than glucose or xylose Hence sports drink contains more fructose, able to empty and
absorb fastero L-Tryptophan is most effective amino acids, hence you’ll feel more full
eating food high in this as it blocks gastric emptying. Tightly controlled rate of 200 kcal/hr into
duodenum o If this rate is exceeded, then there’ll be
diarrhoea
Solid: Size of ingested food (as size of sphincter is v. small)
Function of the stomach is to hold the food!
Intestine absorbs VERY EFFICIENTLY. (Almost no wastage) as it is still adjusted to the past whereby food is
o If drug size is smaller/same as sphincter, it won’t be held at stomach and is hence effective.
Levels of fats, triglycerides, or monosaccharides Liquids are emptied more rapidly than solids in a mixed meal
Vomiting (Abnormal Gastric Emptying) Vomit centre (medulla)
Activated by afferent fibers from stomach, intestinal tract, or other portions of body or irritation due to injury or increases in intracranial pressure (due to head injury); stimulation from higher brain centers and by CTZ.
Projectile vomiting o Not accompanied by nausea (sensation of unpleasantness)
Chemoreceptor trigger zone (brain stem) Activated by afferent nerves originated from GIT or circulating vomitic agents
such as apomorphine or copper sulfate o Relay stimuli to the vomit centre which produces the act of vomitingo Accompanied by nausea
Intestine
Types of Intestinal Motility Segmentation (short range)
back-and-forth movement local reflex
Peristaltic reflex (short range) propel bolus along the entire length of intestine
Migrating motor complex (90-120 min per cycle) housekeeping during interdigestive period - facilitate transportation of
indigestible substance inhibit migration of colonic bacteria into distal ileum
FunctionTo process and absorb nutrients, which requires organized motor activities
Mixing chyme with digestive juices and bile to facilitate digestion and absorption
Propelling chyme in a caudad direction (downwards) Bringing chyme into contact with microvilli
o Transporters are located on the membrane, hence contact between chime and transporters are required.
Transit time 2-4 hrs from one end to the other
o As the intestine is not for holding food, but for absorption, it is faster. Last part of one meal leaves ileum as next meal enters stomach During fasting, mixing and propulsion still occur
o Cleansing of the small intestine (prevent bacteria in the intestine from traveling up)
Ileocaecal Spincter is a valve-like structure that regulates the flow pass ileocaecal junction. Distention of ileum leads to relaxation of spincter while distention of proximal colon lead to contraction of sphincter.
Colon (Large intestine)
Function Storage ***
o Most excreted within 72 hrs Mixing of colonic contents Slow progression of contents distally Non-propulsive
segmentation Retrograde movements Mass movements associated with defecation - mass
peristalsis
Slow Transit Time & Vigorous Mixing Large intestine receives between 0.5 to 2.5 L of chyme
daily from terminal ileum Transit of chyme through large intestine is extremely slow
& variableo This is mainly for the storage of faeces, the
absorption of water and salts is to compact the faeces to store. o 56 hrs for small magnetic spheres to travel from mouth to anus of
which 43 hrs is to traverse large intestine. The slow transit time aids:
Microbial digestion of complex fermentable CH2O in plant residues to volatile short chain fatty acids (good C source for energy, more easily absorbed)
Reabsorption of water & electrolytes to compact faeces Both processes are slow & exacerbated (made worse) by small absorptive
surface area since villi is absent in colonic mucosa
Defecation Mass movements occur a few times a day
o After meal - Gastro/duodeno-colic reflex (Food in stomach will trigger colon reflex)
o Opiates (narcotic opoid alkaloids) decreases mass movements Distention of rectal wall triggers defecation reflex These reflexes cause relaxation of internal anal sphincter (IAS) but contract
external anal sphincter (EAS) o Conscious efforts needed to relax EAS
Abnormal Motility:Incontinence - involuntary excretion of bowel
Sensory malfunction
Incompetence of IAS o Surgical or mechanical factors
Disorder of neuromuscular mechanisms of the EAS & pelvic floor muscles o Surgical or mechanical trauma
Occur during childbirth & ageing Diarrhoea
Increased bowel motility in response to inflammation (oedema, leading to increased volume)
Failure to absorb nutrient molecules effectively (hence increased volume) Excess secretion by small intestinal mucosa (increased volume) Increased volume will trigger the motility due to higher pressure.
Constipation Inadequate fiber in the diet Lack of exercise Slow passage through large intestine leading to further compaction of faeces
(hence faeces become harder and bigger, making it even more difficult to exit)
Repeated voluntary inhibition of defecation reflex
Secretion In the Upper Digestive Tract
Saliva Secretion Produce 1.0 - 1.5 L of saliva each day Salivary glands have a high rate of metabolism and a high blood flow
o Changes to blood flow in body will impact salivary glands, leading to sympathetic stimulation, causing dry mouth.
o Blood flow is 10x that supplied to actively contracting skeletal muscle. Lacking functional salivary glands (dry mouth)
o Dental caries o Infections of bucal mucosa, leading to bad breatho Background secretion is important
Organic constituents:o Mucin (glycoproteins)
Lubricate food o α-Amylase
Active at pH 4-11 o Others in smaller amount:
RNAase & DNAase Lingual lipase Lactoferrin, a globular glycoprotein Secretory Immunoglobulin A (IgA) for immunity Lysozyme, etc
If small intestine is not working, stomach will be responsible for protein digestion. Hence food
cAMP Ca2+
Gastric Secretion, Digestion and Absorption
List of Gastric Secretion
HCl (By Parietal Cells) Kill most ingested bacteria and prevents growth of bacteria
o Helicobacter pylori - ability to neutralise acid by producing ammonia, hence it is responsible for gastric ulcer. (Doctors will therefore give antibiotics for stomach ulcer)
Responsible for cleavage of pepsinogen to pepsins Major Stimulators of HCl Secretion:
o cAMP and Ca2+ as second messengers
cAMP used when under stress (fright/flight), Ca2+ used for maintenance (day to day)
cAMP levels will not be high in the system (as there’s a lot of enzymes to break down cAMP) but Ca2+ levels can be accumulated
o High levels of cAMP makes you alert (#coffee increases cAMP).
Hence anti-histamines will make you drowsy.
o cAMP also increases fluid secretion (both runny nose in flu and gastric HCl secretion)
Hence Anti-histamines will reduce flu but also reduce appetite.
Gastrin (hormone By G cells of gastric antrum) Function of gastrin (uses Ca2+ as 2nd
messenger) Stimulate HCl secretion Increase gastric and intestinal
motility Increase pancreatic secretion For proper growth of GI
mucosa
Pepsinogens (By Chief Cells)Pepsinogen is converted to pepsin (active proteolytic enzyme)
The lower the pH, more rapid the conversion (autocatalytic)
Highest activity at pH <3, hence HCl is important in activating this
Digest 10-20% of total dietary protein Inactivated irreversibly at duodenum pH
Intrinsic factors (By Parietal Cells in Fundus) Glycoprotein For Vit. B12 absorption
o Intrinsic Factor will protect the vit B12 such that it can be absorbed at the terminal ileum by forming a complex that is highly resistant to digestion. Without IF, B12 cannot be absorbed and there’ll be pernicious anaemia.
Only gastric secretion required for life It has same stimulators as HCl (Histamine, ACh and Gastrin) but has no link to
acid secretion (not by the same mechanism). E.g. Omeprezole, a substituted benzimidazole inhibit the ATPase for acid secretion does not affect IF secretion.
Mucins Coat and lubricate mucosal surface, hence protecting gastric mucosa from
mechanical & chemical destruction Main constituent of gastric mucus
o Large molecules (mol. wt 2 x 10^6) with CHO side chains o Insoluble in acid pH
Insolubility leads to precipitation of mucin in the stomach, this makes it harder for enzymes to act on it, requiring a thinner layer to protect the gastric
o Destroyed by pepsin o At pH 5-7, mucin becomes soluble (in the duodenum), hence if acid
leaks into the duodenum, mucin will not be able to protect it. Regulation is by the same mechanism that enhance HCl secretion - ACh and
by mechanical stimulation of food
Prostaglandin E & I Paracrine effects on other gastric mucosal cells
Direct inhibition of acid secretion by parietal cellso Helping to repair (when there’s damage, not secreted when there’s no
damage) Mediate mucosal defence to protect mucous barrier from hostile environment
o Stimulation of mucus, phospholipid (for membrane), and HCO3-secretion
o Enhancement of mucosal blood flow (for oxygen and nutrient supply) supporting mucus
o Stimulation of mucosal cell turnover membrane
Hence, prostaglandin deficiency predispose to gastric mucosal injury (as wear & tear are common in stomach)
Cyclooxygenase inhibitors cause gastric mucosal injuries o E.g. aspirin & nonsteroidal anti-inflammatory drugs (NSAID)
Renin & gastric lipase (enzymes) Not in adults
Ionic Composition Depends on rate of secretion
o Higher the rate, Higher [H+]; Lower the rate, Lower [H+] [K+] in gastric juice always higher than in plasma
Aspirin at pH 2-7 becomes fat soluble. Hence it will cross the membrane and enter the cell. It is then ionised at neutral pH and becomes water soluble. Thus it will be trapped in the cell. And over time aspirin will accumulate. Hence consume after meal where pH in stomach
o Hence when you have prolonged vomiting, a lot of K+ is lost, leading to Hypokalemia
Rate of Secretion Varies considerably among individuals
o Partly due to variations in number of acid secreting cells Basal (unstimulated) rate = 1-5 mM/hr
o This rate is critical: What stomach is prepared to accept Maximum stimulation (when you eat) = 6-40 mM/hr
o Body can handle this as there can be increased antibodies, digestive enzymes, bile to handle the acidity.
Gastric ulcer patient < normal (hypo-secretor of acid)o Feedback mechanism would reduce production of acid to prevent
further damageo Caused by external factors like bacteria infection, alcohol damage,
swallowing without chewing making the stomach grind more leading to mechanical damage.
Duodenal ulcer patient > normal (inhibiting the gastric secretions will help)
Pernicious anemia < normal o Patients secrets less IF. (as acid secretion increases IF secretion since
they have the same stimulator)
Gastric Mucosal Barrier Protect against abrasion, HCl & pepsin (enzyme that breaks down proteins)
Thick mucous layer (1 mm) o Consist of mucins (barrier) & HCO3-
(support: neutralise any acids at the back)
o ★The unstirred layer slows the inward diffusion of H+ & outward diffusion of HCO3-
Mucins facing acids precipitate out, hence there’s no fluid structure for chemical reactions to occur, and diffusion inwards and outwards is hindered.
Depends on mucus & HCO3- secretion Max. HCO3- secretion = 10% of HCl secretion
o Don’t have to neutralise all the acids, as it will then defeat the purpose of secreting acids in the first place. Only to protect the membrane
o As ulcer could be due to infection, whereby bacteria grows in the stomach and peel out the mucous barrier, allowing acids to digest and break it.
Prostaglandin E agonist (misoprostol) o Enhance recovery by stimulating prostaglandin E - it stimulates
turnover of mucosa layer
Digestion Carbohydrate digestion
Depends on the action of salivary α-amylase (from the saliva, continue to function in stomach-those within the bolus)
o Halt at low pH At first the chyme is diluted (pH~5) hence amylase can adapt.
But once volume decrease and pH lowers, amylase will be inhibited.
Prevents amylase from digesting mucinProtein digestion
Break down 10-20% of total dietary protein by pepsin o Protein part of mucin will not be digested (will precipitate out)o If small intestine’s protein digestion is affected, stomach will hold food
longer for protein to digest more, contributing to bigger percentage (it does not produce more pepsin for digeston)
Will lead to indigestion (since difficulty to digest at normal amount of time)/diarrhoea
Fat digestion Minimal High acidity inhibit fats from forming emulsion (emulsion is not soluble,
cannot be transported)o Fats can pass through the cell (hence not much digestion needed)o Insolubility ( and anything insoluble cannot be digested)
Absorption Nutrients
Very little absorption take place (as function of stomach is to hold the food) Only highly lipid-soluble substances (can be absorbed without help)
o Ethanol is rapidly absorbed as it is fat soluble Alcohol consumed will be absorbed (not held at stomach), thus
will get quickly intoxicated.
HeartburnGastritis : A painful or burning sensation in the chest
An increase in gastric acid secretion Backflush of acidic chyme into esophagus or the weakening of lower
esophageal sphincter (esp in older people)o May cause inflammationo Should then drink water and washdown the acid to prevent damage to
esophagus Causes
Overeating, smoking Fatty foods (cause indigestion as it stays in the stomach), coffee, alcohol
Increase pressure Lying down immediately after meal lead to
back flush Tight clothing
Stomach is very near the heart, hence if a lot of acid comes out through esophagus, there’s a burning sensation.
Cl- channels are used to secrete fluids (# tears, sweat, saliva) by drawing out water through its osmotic influence. This is done by pumping Cl- out of cell, where these ions are used to form salts to create osmotic pressure that draws water out.
Na+ is not used as it draws water into cell (rehydration therapy). The presence of Na+-glucose cotransporter allows
In secretion, Cl- channel open, Na+ drawn out to balance the membrane potential, drawing water out by change in osmotic pressure. This uses cAMP as 2nd messenger to open Cl- channel (sensitive to it).
Small Intestine Secretion and AbsorptionOverviewAbsorption of nutrients is the principal task of digestive system
Absorption is almost entirely accomplished by small intestine o Small intestine is in excess (ileum is only in case some substance slip
past)o Large surface area o Absorption site and conditions change as transporter mechanisms
differ Duodenum (12 fingers long, not as effective in absorbing as
jejenum) and upper jejunum - fast absorption rate: high capacity, very fast, but less specific.
At ileum site (lower conc of nutrients): it is slower, more specific and higher affinity
Secretion Mucus
Protect surface against acid & pepsin Stimulated by parasympathetic nerve impulses & 3 major GI hormones
o Gastrin in the stomach o Cholecystokinin (CCK ) in pancreaso Secretin in pancreas
Enzymes As a result of cell degeneration (broken down from dead cells) not secretion
(unlike from glands) Complete turnover of epithelial cells occurs in 2-3 days and dead cells release
their content: o Maltase o Sucrase o Lactase o L-Glucosidase o Enterokinase, etc
Contains many pancreatic enzymes
Intestinal juice 2-3 L/day (hard to measure as a lot is secreted and
absorbed back) o Under normal conditions only net absorption
of fluid by osmotic pressure of cation, Na+ Cl- channels inactive - opened when
secretion(in diarrhoea the channel is activated and fluid is lost.)
Isotonic to plasma o Higher HCO3- & lower Cl- than plasma
HCO3-/Cl- exchanger: uses Cl- to exchange to HCO3- such that neutrality is maintained.
Stimulation
o Mechanical irritation of the mucosa: food presence irritates the mucosa’s mechanical receptors
o Distension of the gut o ACh & gastrin
Ca2+ (messenger - appear first)
o Secretin, CCK & GIP cAMP (come later, linked to
stress pathway, hence should not overeat)
Function o Fluidity of the chyme o slight alkaline pH (acid from
stomach needs to be neutralised so that transporters can take up the food and enzymes can function.
Intestine will absorb everything first then kidney organises and regulates. If got extra, then will pee out.
If drug at a particular pH remains un-ionised then no transporter is required as it can cross cell membrane. But if polar, then transporter is required.
Drugs also need to be water
AbsorptionCaloric Absorption
Highly efficient Rate of caloric absorption can only adjusted at ingestion step (more eaten,
higher rate)o Calcium and iron are partially absorbed because body cannot absorb
them efficiently 3 Ways to increase surface area (as intestine function for absorption)
o Folds o Villi o Microvilli
Water and Electrolytes AbsorptionAbsorbed 99% of water & electrolyte present to them
Failure will lead to rapid dehydration (as salt absorbed is used to drive water reabsorption) & circulatory collapse (for infants as they don’t have enough ECF volume).
o Blood pressure may drop.Amount defecated per day:
100 ml water, 3.5 mM Na+,1.5 mM Cl-,13 mM K+ (potassium present in our diet, so can afford to lose more)
25 to 50 g solids Once sodium absorbed, it is preserved and hardly removed.
Water transport is regulated by regulation of electrolyte transport Play a minor role (as its main role is not to absorb water, that’s the role of the
kidneys) in normal regulation of water, electrolyte & acid-base homeostasis Small intestine reabsorbs a lot of water to make up for all the secretions.
Interference along this path will result in loss of this water (8500ml per day of absorption), and cause bad diarrhoea with fast onset. (liquid excretions)
o If the diarrhoea isn’t that bad then it is probably due to the colon (#food too spicy)
pH & Drugs Absorption pH varies throughout the GIT
1.5 - 8 (> 1000,000x difference in terms of H+ conc.)
Un-ionised form (non-polar) is more lipid soluble
pH affects % un-ionised Drugs and disease may affect pH (impt for drug discovery)
Colon Secretion and AbsorptionOverview~ 90-150 cm long
No villi (absorption done in small intestine)
If you don’t absorb fats properly it is not as serious, as fats are not osmotically active.
The Cl- channels pump Cl- out such that there’s osmotic negativity and Na+ will be drawn out. They form NaCl, creating osmotic
Microflora (symbiosis) present Viscous material
[in liver failure, patients may die of ammonia build up in blood. Diet control and control of microflora which produces ammonia are both require]
Secretion Mucus
Functions similar to that of small intestine Intestinal juice
High K+(used to absorb water and exchange for Na+) & HCO3- (pH 8.0-8.4) o Not a major K+ excretion site (not meant for secretion but for Na+
exchange only)o Buffer against H+ produced by bacterial fermentation (may be slightly
acidic from it) Stimulation
o Parasympathetic nerve impulses Sympathetic nerve impulses decrease secretion (as
sympathetic uses cAMP which stimulates water secretion, and sympathetic also causes vasoconstriction)
o Mechanical or chemical irritation of the mucosa (part of defence mechanism)
Pathological Alterations of Salt & Water Absorption Failure to absorb an electrolyte normally
Congenital Cl- diarrhoea o Lacking Cl-/HCO3- exchanger leads
to retention of HCO3- that cause metabolic alkalosis
Failure to absorb a nutrient normally Most common in carbohydrates as they are v osmotically active (will give a
lot of problems in water and salt absorption)o CH2O (carbo) malabsorption syndromes
Hypermotility of intestine Less absorption time
Enhanced secretion of water & electrolytes
Secretory diarrhoea o 10-20 L water/day o 2 types of Cl- channels
Ca2+- or cAMP-sensitive
Oral rehydration therapy Glucose- or a.a.-saline solution: cotransporters will
cotransport these w Na+ to draw water in. Cannot exceed 1M (18%) glucose.
Pancreatic SecretionPancreatic cell types & their functions
Contains endocrine, acinar, ductal and goblet cells Endocrine cells secrete:
o Insulin o Glucagon o (Somatostatin) o Pancreatic polypeptide
Acinar cells secrete enzymes: o Peptidases, lipases, α-amylases, & nucleaseso Failure to secrete leads to malabsorption syndromes
Ductal cells secrete: o 1.2-1.5 L/day pancreatic juice
High [HCO3-] to regulate the pH of upper intestine, failure will lead to duodenal ulcers (no HCO3- to neutralise the acidic chyme)
o To release gastrin by G cells Gastrin produces low-volume high-enzyme pancreatic secretion
3) Intestinal phase Most important phase
o 70% of total secretion is triggered at this phase Stimulated by CCK & secretin (after gastrin)
o Release from endocrine cells in duodenum & upper jejunum CCK is potent stimulant of pancreatic enzyme secretion
o Potentiated by secretin (secretin enhance effects of CCK) However, by itself, secretin has no effect on CCK secretion
Secretin is to increase HCO3- secretion by pancreas o Potentiated by CCK
However, by itself, CCK has no effect on secretin secretion o Secretin & CCK work synergistically
Ach using the Ca2+ pathway potentiates the effects of both CCK & secretin that uses the cAMP pathway
o Vagal stimulation is much more potent in stimulating pancreatic secretion when CCK & secretin are present in plasma
Control of secretin & CCK secretion o Response to entrance of chyme into small intestine o Amino acids (mainly phenylalanine & tryptophane which are very potent),
fatty acids & monoglycerides are major stimuli for CCK secretion o Low pH (<4.5) a potent stimulus for release of secretin (as secretion
increases HCO3- secretion)
Digestion and Absorption of Carbohydrates
Digestion CH2O must be digested into monosaccharides before being absorbed. This
occur in 2 steps, luminal digestion by α-amylase and mucosal digestion by brush border enzymes.
Starch digestion begins in mouth (salivary α-amylase) o Almost all digestion occurs within small intestine o Pancreatic α-amylase most concentrated in duodenum
α-Amylase digests CH2O into a variety of oligosaccharides Oligosaccharides are then converted to monosaccharides by brush border
enzymes (microvili bound enzymes) o Rate-limiting step in CH2O absorption o The enzyme activities are greatest at brush border of jejunum o End products:
CCK will increase to make sure there’s enough pancreatic lipase to emulsify the fats as CCK stimulates pancreatic enzyme
CCK by lipid presence
Secretin by low
Fructose Glucose Galactose
Absorption Duodenum (first part of small intestine) & upper jejunum have the highest capacity to absorb sugars as they contain the most number of transporters.
Mechanisms of absorption: o Glucose, galactose & xylose are absorbed by a common Na+-
dependent transport system (secondary active transport - SGLT)o Fructose is absorbed by facilitated transport
Most of the fructose is rapidly converted into glucose & lactic acid within epithelial cells (hence removing fructose from epithelial cells)
This maintains a concentration gradient for diffusion
The monosaccharides are transported across basolateral membrane by facilitated transport
Monosaccharide absorption isn’t regulated o Can absorb over 5 kg sucrose a day
Failure to absorb CH2O results in diarrhea (as carbohydrates are osmotically active) & intestinal gas (H2, CO2, CH4) as carbohydrates in colon will be fermented by bacteria.
Note: Solvent drag through gap junctions may bring some glucose in as well. SGLT being Na+ dependent can be used as a means to rehydrate the body (since Na+ exert osmotic pressure)
Lactose IntoleranceAutosomal dominant trait (one parent is enough to pass on the gene)
Lactase drops to 5-10% of childhood levels As the milk/sugar cannot get absorbed, they stay in
the lumen, increasing pressure and volume, causing distention that leads to motility and diarrhoea.
Lactase is sensitive to infectious & inflammatory diseases that affect intestine (Hence when patient is sick, they cannot drink milk or they may get diarrhoea)
Digestion and Absorption of Proteins
Digestion Protein digested into small polypeptides & a.a before being absorbed
Di, tri & tetrapeptides are 3-4 x more concentrated than single a.a. inside enterocytes
o This is because short chain peptides are transported faster than single amino acids, able to be absorbed not as single amino acids only (unlike monosaccharides)
Enzymes: Gastric pepsin
o Digest 10-15% of protein Pancreatic proteases (BULK) Enterocytes peptidases
About 50% protein is digested & absorbed by duodenum & jejunum
20-50% reaches ileum 10% reaches colon
o Digested by micro-organisms (feed the bacteria)
Protein in stools is from bacterial & cellular debris, not from food.
AbsorptionNa+-dependent transport systems for tri-, dipeptides & L-a.a.
Tripeptides & dipeptides are absorbed in greater quantities than a.a. Almost all ingested protein is absorbed by intestine Hydrolysed intracellularly to form amino acids.
Digestion and Absorption of Lipids
Biliary Secretion (ongoing)Bile functions
Digestion & absorption of fats - emulsify fats to make more water soluble for lipase to act on
Excretion of water-insoluble substances - fat soluble substances dissolve in bile to be excreted
o Cholesterol & bilirubin
Composition of Bile1) Bile acids
1° bile acids (in small intestine)o Cholic & chenodeoxycholic acids
Synthesized from cholesterol
Bile formation By hepatocytes
(liver) & ductal (bile duct) cells
3-4g/dl
Bile storage In gall bladder
during interdigestive period
10-15g/dl
Bile release Chyme triggers CCK
release, which subsequently
stimulates gallbladder contraction
More water soluble than cholesterol (hence stay in lumen as it is water soluble, and is only reabsorbed at terminal ileum)
Actively reabsorbed at ileum 2° bile acids (in colon) (carcinogenic)
o Deoxycholic & lithocholic acids Deconjugation & dehydroxylation of 1° bile acids (those not
reabsorbed) by intestinal bacteria to make them fat soluble again (such that they can cross membrane and thus be reabsorbed)
2) Bile pigments Bilirubin & biliverdin
o Metabolites of hemoglobin o For excretion o Responsible for yellow colour of bile
Bacteria convert bilirubin to urobilin o Brown colour of stool o Hence if stool is yellowish, it means there’s less bilirubin to be
converted, hinting a problem with bile secretion. (# gallstones causing blockage)
3) Phospholipids (mostly lecithins, which enhance power of bile) 2nd abundant organic bile compound Amphipathic, hence it increases cholesterol solubilization in bile micelles (as
bile salts are steroids and are hence rigid and unable to accommodate another cholesterol well.
o Major route for cholesterol excretion Stabilizing the crude triglyceride emulsion
4) Electrolytes Isotonic to plasma
o [HCO3-] > plasma to neutralise pH
Conjugation of Bile Acids Bile acids are conjugated with glycine or taurine to form bile salts
Enhance the hydrophilicity Taurine more hydrophilic than glycine
Makes it more amphiphatic Easier to form micelles - aid fat absorption Reabsorb poorly - stay longer in gut (until
transporter at the end of the ileum) Resistance to hydrolysis by pancreatic enzymes (hence it can stay intact in the lumen)
Enterohepatic CirculationRecycle bile from small intestine to liver and back again
Only limited pool of bile salts (3.6 g) Reabsorbed only in terminal ileum
80-90% reabsorbed Remaining are excreted into feces
Need 4-8 g bile in each meal
Colon cancer is caused when you eat a lot, and there’s a lot of bile acid utilization. Hence a lot of them cannot be reabsorbed at ileum and will become 2° bile acids. Prolong exposure to the carcinogenic 2° bile acids
Total pool recirculate twice per meal Rate of synthesis is determined by rate of return to liver (if there’s more return, less synthesis is required)
EmulsificationFat must be soluble in water for digestion & absorption
Bile acts a detergent Lecithin increase detergent power of bile
Cholesterol Solubility in Bile When it is in micellar liquid form, cholestrol can be transported and excreted. Without the correct composition, gall stones may form.
Extremely hydrophobic materials (cholesterol & fat-soluble vit.) are within the interior of micelle
Need minimum amount of bile salts
Absorption of lipids from micelles Lipids are removed rapidly once
contacted with microvilli o Hence, the rate limiting step is the
migration of micelle from chyme to microvilli surface
Bile salts are actively reabsorbed at terminal ileum such that all ingested lipid is absorbed
Fat in stools is from colonic bacteria & desquamated intestinal cells
>95% coefficient of absorption for triglyceride Cholesterol absorption is slowest
Increase plant steroids can decrease cholesterol absorption
Post- Absorptive (Delivery)
Re-esterification Formation of chylomicrons (lipoprotein particles) for re-esterified lipids Lymphatic transport No re-esterification for Medium Chain Fatty Acids (6-12 Cs) and Short Chain Fatty
Acids (<6 Cs) SCFA is a bacterial source with no micelle and chylomicron formation
