GASTROINTESTINAL PHYSIOLOGY

Ingestion of food is controlled by hunger and appetite. In health the body controls the rate at which ingested food moves through the GI system, so that digestion and absorption are optimised. The first residue from a meal will pass through the GI system in 7-10 hours, but some may take up to 5 or 6 days to pass through.

Ingested food pass through the mouth, esophagus, stomach, small intestine, (duodenum, jejunum, and ileum), and the large intestine (colon) before exiting the body.

THE GI WALL HAS FOUR LAYERS.The basic structure of the GIT wall is similar

in the stomach and intestine though with some variations between different sections of the GIT.

An inner layer—mucosa a middle layer--- submucosaAn outer layer---muscle Cover-----------serosa

I. THE MUCOSAThe inner lining of the GIT created from;A. A single layer of epithelial cellsB. Lamina propria, subepithelial connective tissue that

holds the epithelium in placeC. Muscularis mucosa, a thin layer of smooth muscle .Several modifications have evolved to increase the

amount of surface area that is contained within the lumen.

1st entire wall is crumpled into folds –the rugae in the stomach and plicae in the intestine. Intestinal mucosa also projects into the lumen in small fingerlike extensions-villi

Additional surface area is created by tubular invaginations of the surface that extend down into the suppository connective tissue. These invaginations are gastric glands in the stomach and crypts in the intestine. Some of the deepest invaginations form secretory submucosal glands that open into the lumen through ducts

The surface area of each individual cell is increased by microvilli along apical membrane

II. THE SUBMUCOSAMiddle layer composed of connective tissue

with larger blood and lymph vessels. It also contains, submucosal plexus, (meissner’s) one of the 2 major nerve networks of the enteric nervous system. The enteric NS is a unique division of the nervous system that helps coordinate digestive functions

iii. MUSCULATUREThe outer wall of the intestinal tract consists

mostly of 2 layers of smooth muscle, an inner circular layer, and an outer longitudinal layer. Contraction of the circular layer decreases the diameter of the lumen , and contraction of the longitudinal layer shortens the tube.

Myenteric plexus (Auerbach’s) which is the second nerve network of the Enteric NS lies between the two muscle layers

Iv. THE SEROSAThis is the outer covering of the GIT

Principles of GI FunctionNeural Control of GI FunctionThe gut is controlled by its own nervous

system the Enteric nervous system, Autonomic nervous system

(parasympathetic and sympathetic) Endocrinal Control of GI Function Several hormones.

ENTERIC NERVOUS SYSTEMContains all the neural elements required for complex

integrative function and behaves like a “little brain “ in the generation and modulation of phasic patterns of neuronal activity. It programs and regulates all GI functions. The 2 peripheral plexuses of the ENS are

the submucosal (Meissner’s) plexus located within the submucosa , is more involved with local conditions and controls local secretion, absorption and local movements

Myenteric (Auerbach’s) plexus located between the circular and outer longitudinal muscle layer. MOTILITY throughout the whole gut. Stimulation of the plexus increases the tone and velocity and intensity of the contractions. Inhibition helps relax the sphincters

The mucosa and epithelium have sensory

nerve endings that feed signals to the both layers of the enteric plexus as well as sending information back to the sympathetic pre- vertebral ganglia, the spinal corn and to the brain stem. Numerous transmitters seem to be involved, the more important of which are acetylcholine and norepinephrine. The former excites, the latter inhibits it.

EXTRINSIC NERVESI. PARASYMPATHETIC FIBERS are supplied by the

vagus nerve and pelvic nerves which are of sacral origin. Parasympathetic fibers are cholinergic and innervate both plexuses of the enteric NS. Increased parasympathetic activity increases smooth muscle activity. Motility and secretion is increased, there is a reduction in constriction of sphincters. An increase in parasympathetic activity promotes digestive and absorptive processes.

The proximal half of the nervous system is innervated from the cranial parasympathetic nerve fibers via the vagal nerve. The distal half is innervated via Sacral Parasympathetic nerves, which gives supply to the sigmoid colon, rectum and anus, and are important in controlling defecation

SYMPATHETIC INNERVATIONThe fibers originate in the sympathetic ganglia of T-5

to L-2 and terminate on the enteric nervous plexus, but also a few nerves terminate in the mucosa it self

SYMPATHETIC FIBERS innervation of the GI is noradrenergic postganglionic. Increased sympathetic discharge inhibit acetylcholine secretion from cholinergic neurons.

Some sympathetic fibers innervate smooth muscle cells directly and some innervate splanchnic blood vessels and act to cause vasocostriction, leading to decreased motility and secretions, increase in constriction of sphincters.

Afferent Sensory InnervationNumerous afferent sensory fibers innervate

the gut. Some have their cell bodies in the enteric plexus, and some in the spinal cord. As well as sending information concerning irritation and over distension, they can also pick up the presence of chemical signals in the gut. 80% of the fibers in the vagus nerve are afferent, and these send signals all the way to the medulla for processing

Gastrointestinal ReflexesGI reflexes can be considered;1. Local2. Regional3. SystemicLocal reflexes are processed entirely within the enteric

system and control secretion, local motility, and mixing contractions.

Regional reflexes go to the sympathetic ganglia, and are important for reflexes at a distant, such as the gastro- colic reflex causing evacuation of the colon, and messages from the intestine to the stomach to inhibit emptying, the entero- gastric reflex, or the colono- ilial reflex that inhibits emptying of the ilial contents into the colon.

Systemic reflexes are processed in the spinal cord or brainstem and will control overall activity f the GI system, for example pain reflexes that will inhibit the entire GI system.

Hormone Source Stimulus Stomach Motility and Secretion

Pancreas Gall bladder

1. Secretin S cells lining the duodenum

Acid entering duodenum

Inhibits Stimulates fluid secretion (HCO3

-)2. CCK Cells lining the

duodenumFat and amino acids entering duodenum

Inhibits emptying

Stimulates enzyme secretion

1. Contraction2. Relaxation

sphincter (Oddi)

3. Gastrin G cells of stomachAntrumDuodenum

Stomach distensionParasymp Peptides Stomach acid inhibits

Stimulates

4. GIP Duodenum Fat, CH0, amino acids

Inhibits

CCK = Cholecystokonin, GIP = Gastric inhibitory peptide (glucose insulintropic peptide)Note: In a non-acid producing stomach (e.g, chronic gastritis), the reduced negative feedback increases circulating gastrin.All four hormones stimulate insulin release.

MOTILITYIn the GIT serves 2 purposesI. Moving food from mouth to the anus II.Mechanically mixing food to maximize

exposure to digestive enzymes and the absorptive epithelium.

Most of the intestinal tract is composed of single unit muscle whose cells are electrically connected by gap junctions

Certain intestinal muscle cells act as pacemaker and exhibit spontaneous depolarization which is similar to pacemaker of the heart. These generate slow wave potentials at a rate of 8-11 per minute. When the slow wave reaches threshold, it fires a battery of AP’s that spread through gap junctions to adjacent muscle cells. The longitudinal layer of muscle conducts these action potentials along the length of the GI tract, creating a wave of contractions.

Smooth muscle is unique in that it can contract even without a significant change in membrane potential. This occurs when a chemical ligand such as hormones or drugs combine with membrane receiptors that either open Ca++ channels in the muscle cell membrane, or cause release of Ca++ from the SR. This type of contraction is termed pharmacomechanical coupling.

SMOOTH MUSCLE CHARACTERISTICSSmooth, also called involuntary or un-striated

muscle is usually found in the walls of the hollow organs, and have many unique characteristics. Contraction of these cells is due an influx of Ca++ ions. In the gut three types of contraction are seen;

Tonic sustained contractions such as occur in sphincters

Peristaltic contractionsSegmental contractionsBy a variety of these contractions, food and

chyme is moved through the bowel.

TONIC, SUSTAINED CNTRACTIONThese type of contractions occur in rings or

bands of muscles- sphincters that separate different sections of the digestive system.

There are several sphincters , upper and lower esophageal sphincters which close off the 2 ends of esophagus

-the pyloric sphincter located between the stomach and the small intestine.

-the sphincter of oddi- which controls the flow of bile and pancreatic juices into the small intestine

-ileocecal sphincter found between the small intestine and the large intestines.

-internal and external anal sphinctersThe upper esophageal and the external anal

sphincter are composed of skeletal muscle, and the remaining 5 are smooth muscles

All sphincters are tonically contracted . When they relax material is able to pass from one segment of the GI to another

PERISTALTIC CONTRACTIONSThese are progressive waves of contractions

that move from one section of the intestinal tract to another.

-this movement is responsible for the rapid forward propulsion of material through the tract.

The forward movement of material with peristaltic contraction occurs at a speed of between 2 and

25 cm/sec

In the peristaltic Reflex, peristaltic waves are triggered in isolated segment of the intestine by distention of the wall. This reflex is mediated strictly through the enteric NS- peristalsis is also subject to external control by hormones, paracrines and ANS

SEGMENTAL CONTRACTIONThese are mixing contraction that knead

material back and forth without propelling it forward at a very fast rate . In this segment contraction alternative segments of intestine contract and relax, propelling material short distances in both directions.

Segmental contractions – churn the intestines contracts back and forth mixing them and keeping them in contact with absorptive epithelium.

MECHANICS OF CONTRACTIONSmooth or un-striated muscle cells contract

by altering their shape. They contain numerous actin-myosin bundles. Some of the strands attach to the cell, they are all anchored to the dense bodies in the cytoplasm of the cell. On activation the actin strands slide over the myosin causing shortening of the actin-myosin bundle.

MOTILITY THROUGHOUT THE GI SYSTEM The passage of food through the gut, its

conversion to chyme, and finally feces is all under involuntary control. Only the first part –ingestion and swallowing, and the last part – defecation are under voluntary control.

MASTICATIONChewing is extremely important part of the

digestive progress especially for fruits and vegetables as these have indigestible cellulose coats which must be physically broken down . Also digestive enzymes only work on the surfaces of food particles, so the smaller particle, the more efficient the digestive process

SWALLOWINGSwallowing is coordinated by the swallowing

or deglutition center located in the lower pons. Impulses are carried by the Trigeminal, Glossopharangeal, and Vagus nerves.

STAGES has 3 stagesThe 1st stage-Oral/buccal voluntary2nd stage-pharyngeal3rd stage Eosophageal involuntary

SWALLOWING I. The tongue pushes a bolus of food against the

soft palate triggering the swallowing reflex.II. The soft palate is pulled upwards preventing

reflux of food into the nasal cavitiesThe vocal cords are strongly approximatedThe larynx is pulled upwards, closing the

epiglottis, preventing food entering the trachea. The esophageal sphincter relaxes.

The muscular wall of the pharynx contracts beginning superiorly, pushing the food into the esophagus

III.Peristaltic waves assisted by gravity push the food down the esophagus.

ESOPHAGUSFood is carried down the esophagus by

peristaltic contractions. If these are insufficient to move all the food, stronger secondary peristaltic waves develop. These are initiated by both the myenteric plexus and centrally

The muscle at the lower end of the esophagus thickens and is called the lower esophageal sphincter. This is usually tonically contracted, but relaxes when the peristaltic wave reaches it, allowing passage of food into the stomach.

STOMACHFood entering the stomach passes into the fundus

of the stomach where it is stored. Weak peritaltic waves known as mixing waves originate in the upper stomach and pass down to the antrum. These waves become stronger as they approach the antrum, and as they push the food against a closed pylorus they also act as mixing waves. Food in the antrum of the stomach is also thoroughly mixed with segmental contractions. The mixed fluid contents are called chyme, and amounts of this are pushed through the pylorus into the duodenum with the stronger peristaltic contractions.

Control of stomach emptyingT he rate of emptying of the stomach is controlled by

various factors originating in the duodenum and stomach, of which the duodenal factors are the most important.

Gastric factors include increased volume of food in the stomach and stretching of the stomach wall. The hormone Gastrin also appears to promote stomach emptying

Duodenal factors serve mainly to inhibit entering , thereby ensuring that the intestine is not overwhelmed by sudden influx of acidic chyme. They include nervous reflexes and hormones. The nerve reflexes are transmitted both by the enteric nervous system and through extrinsic nerves via the pre-vertebral sympathetic ganglia.

Control of Stomach Emptying cont..Factors that inhibit emptying include Distention of the duodenumThe degree of acidity of the duodenal chyme The osmolarity of the chymeIrritation of the duodenumThe reflexes are particularly sensitive to acidity and

irritation which cause rapid inhibition of the stomach emptying

Hormones that inhibit emptying include cholecystokinin, secretin, Gastric Inhibitory Peptide (GIP) Secretin is secreted in response to acidity in the duodenum, Cholecytokinin and GIP response to the presence of fats in the chyme

All these factors ensure that the rate of stomach emptying is limited to what the small intestine can process.

SMALL BOWELIn the small intestine mixing with segmental

contractions continues and the food is slowly passed through the intestine , finally passing through the ileo-caecal sphincter to the large intestine, to a large extent the separation of segmental contractions from peristaltic contractions is artificial as both serve to move chyme forward and both add to mixing. Chyme moves down the small intestine at a rate about 1 cm/min, so will reach the ileocaecal junction in 3-5 hours. It often stays there till the next meal the gastroileal reflex intensifies peristalsis in the distal ileum forcing chyme through the ileocaecal valve.

Small Bowel cont.Intensity of peristalsis is controlled by both

neuronal reflexes and hormones. Neuronal factors include distension of the intestine wall, but also distension of the stomach will also cause increased small intestine peristalsis. Both of these reflexes are mediated by the mesenteric plexus.

Hormonal factors increasing peristalsis include gastrin, CCK, insulin, motulin and serotonin.

Glucagon and secretin inhibit peristalsis.

Ileocaecal valveT he prime function of the ileoceacal valve is to

prevent reflux of fecal contents into the small intestines. The valve protrudes into the caecum, thus increased ceacal pressure will cause occlusion. Furthermore, the muscle is thickened for a few centimeters from the distal end of the ileum, and this acts as a functional sphincter.

Increased pressure or irritation in the distal ileum will cause relaxation, increased caecal pressure or irritation will cause constriction.

LARGE BOWEL and DEFECATIONThe principle function of the large intestine is to

remove water and electrolytes from the chyme, and to store the resultant faeces until it can be eliminated.

In the colon the longitudinal muscle coat is condensed into three narrow bands called taenia coli.

Thus mixing movements of the circular muscle coat , so called haustrations predominate . These will also slowly move the contents towards the rectum.

Much of the movement comes from haustrations, but is the third type of contraction called mass movement which sends substantial amounts of material forward. These typically occur 2-3 times a day, usually after a meal- the so called gastrocolic reflex, and last for about 20 minutes. They are responsible for the final formation of the faeces and the filling of the rectum.

Filling of the rectum is a signal for the relaxation of the Internal anal sphincter. However the External anal sphincter is under voluntary control.

Although the myenteric defecation signal only weakly relaxes the Internal anal sphincter, the stronger signal comes from parasympathetic reflexes synapsing in the sacral cord .These can be inhibited centrally, and when time to defecate is convenient, the inhibition is released, and the external anal sphincter, under voluntary control is relaxed.

The sequence of defecation is often initiated voluntarily; the epiglotis is closed a deep breath, and contraction of the abdominal muscles increase intra-abdominal pressure.

Coordination of motilityAll these actions are coordinated, and are

under control of hormones, and the autonomic nervous system as well as the enteric nervous system, the result is that in health food products and chyme are moved forward at the optimal rate to allow for efficient digestion and absorption.

GASTROINTESTINAL SECRETIONSSecretions in the GI tractAbout 9 L of fluid pass through the GI system

each day, and only about 2 L are ingested, the rest represent secretions from the system itself. About 3.5 L is secreted from the exocrine glands, the salivary glands, the pancreas and the liver, and other half is secreted by the epithelial cells of the digestive tract it self. Nearly all this fluid is absorbed, so the pellets of feces only contain a significant amount of fluid in diarrhea.

To put this in perspective a 70 kg man has 42 L of fluid, so the secretions represent about a sixth of the body’s volume. The circulation contains about 3.5 liters, so these secretions represent twice the body’s circulating volume! Failure of absorption of the intestinal secretions can thus lead to rapid dehydration and electrolyte imbalance.

The secretions consist of digestive enzymes, mucous and substantial amounts of fluid and ions.

Daily Volume (ml) pHSaliva 1000 6.0- 7.0Stomach 1500 1.0-3.0Brunners Gland 200 8.0-9.0Pancreas 1000-1500 8.0- 8.3Bile 1000 7.8Small Intestine 1800 7.5-8.0Large Intestine 200 7.5-8.0Total 6700-7200

Types of glands Several different types of gland and are found in

the GITSingle cell mucous glands and goblet cells.Pit glands. Invaginations of the epithelia into the

submucosa. In the Small intestine these are called Crypts of Lieberkuhn

Deep tubular glands. These are found in the stomach – the gastric glands, and the upper duodenum-Brunners glands.

Complex glands, the salivary glands, the pancreas, and the liver. The salivary glands and the pancreas are compound acinous glands.

Mechanisms of stimulationStimulation occurs due to local effects;

autonomic stimulation; and hormonesLocal effects The mechanical presence of food causes

stimulation not only locally but also adjacent regions. This may either be a direct effect, or via the enteric nervous system.

Autonomic StimulationStimulation of parasympathetic nerves serve

to increase secretion. Stimulation of sympathetic nerves may increase some secretions, but usually diminish blood flow, which will usually decrease overall secretion

HormonesSeveral different hormones affect secretions

Digestive EnzymesDigestive enzyme are secreted by glandular

cells which will store the enzyme in secretory vesicles until they are released. These cells are characterised by a robust rough endoplasmic reticulum and numerous mitochondria. Passage of materials from the ribosomes, through the endoplasmic reticulum and Golgi body to the secretory vesicles takes about 20 minutes.

Water and Electrolyte secretionsGlandular secretions must also secrete water and electrolytes to go along with the organic

substances.In its resting state the membrane resting potential

is about -30 -40 mV.Neural stimulation causes an influx of -ve chloride

ions decreasing resting potential by 10-20 mVSodium ions follow down the electrical gradient.

Cell contents become hyper osmotic Water follows. Intracellular pressure increases.Increased pressure opens ports on the apical side

of cell flushing water and electrolytes

Mucus Secreting CellsMucous is viscous secretion used for

protection and lubrication. It consists mainly of Glycoproteins. It is made by mucous cells in the stomach and Goblet cells in the small intestine. Up to 25% of the intestinal epithelial cells are goblet cells. In the mouth about 70% of the mucous is secreted by the minor salivary glands.

Mucous has the following properties:Adherent properties, it sticks well to surfacesEnough body to prevent contact of most food

particles with tissue.Lubricates well- has a low resistance to

slippageStrongly resistant to digestive enzymesNeutralizing properties..As well as a buffer

like effect, mucous can also contain large quantities of bicarbonate.

Electrolytes and FluidsA large portion of the 7 liters is composed of water and

ions. The ionic composition varies from region to region.

The acini of the salivary glands secrete a sodium and chloride rich secretion, this is then turned to a potassium, bicarbonate rich secretion as it travels down the lumen and ducts of the glands.

The oxyntic cells of the stomach secrete hydrochloric acid

The mucous cells of the stomach secrete mucous rich in bicarbonates

The pancreatic ducts and ductules secrete a solution rich in bicarbonate

The Crypts of Liberkuhn of the intestine secrete a solution almost indistinguishable from intestinal fluid

MOUTHThe salivary glands consist of the Parotid,

submandibular, and sublingual as well as numerous smaller buccal glands secreting both serous and mucoid secretions. The parotid secretions are mainly serous, the buccal glands mucus, and the sublingual and submandibular are a mixture of the two. The acini secrete proteins and a fluid similar in consistency to interstitial fluid, and the ducts exchange the sodium for potassium and bicarbonate for chloride leaving saliva rich in potassium and bicarbonate.

The saliva secrete between 800- 1500 mls a day.

The sodium ions are actively reabsorbed, and the potassium ions are actively secreted at the luminal side of the cell with an excess of sodium reabsorption causing a – 70m V gradient. This causes passive reabsorption of chloride ions. Bicarbonate ions are both passively exchanged, and actively secreted in exchange for chloride.

The saliva contains enzyme ptyalin, an amylase for breaking down carbohydrates as well as lipase.

Anti bacterial action of SalivaThe mouth contains numerous bacteria, and an

important function of saliva is oral hygiene. The saliva contains thiocyanate, a potent antibacterial. The lipase in saliva will also breakdown bacteria cell walls and facilitates the passage of thiocyanate into bacteria.

The enzyme lipase is not very important for the digestion of food, most of fat digestion occurs with the pancreatic enzymes, but is important in its antibacterial and oral hygiene role

Regulation of Salivary Secretion.Salivation is controlled via the parasympathetic

system from the salivary nuclei in the brain stem. Factors that induce salivation include;

Taste stimuli, especially sour tasteHigher centers especially appetite anticipation,

smells and visual cluesIn response to signals from the stomach and

upper GI tract, particularly irritating stimuli.Salivation can also occur as a prelude to

vomiting.

EsophagusEsophageal secretions are entirely mucous in

character, and assist passage of food as well as protecting the lower end of the esophagus from gastric reflux.

StomachThe adult stomach secretes about 1500 ml in a normal

day consisting of hydrochloric acid, bicarbonate rich mucous, and the digestive hormone precursor pepsinogen.

Pepsinogen is activated to pepsin by the acidity of the stomach. G cells also secrete the hormone gastrin.

The gastric pits of the stomach open on to branching glands; pyloric glands in the antral part of the stomach; gastric or oxyntic glands in the fundus and body of the stomach.

The parietal or oxyntic cells secrete hydrochloric acid; the peptic or chief cells secrete pepsinogen; the mucous cells secrete a bicarbonate rich mucous; and the G cells secrete the hormone Gastrin.

Hydrochloric Acid secretionThe oxyntic or parietal cell contains a large

number of intracellular canaliculi. The pH of the secreted acid is 0.8, and has hydrogen ion concentration of about 3 million times that of arterial blood. To achieve this level of concentration requires a lot of energy, about 1500 calories per liter of secretion

Mechanism of Hcl Secretion Carbon dioxide and water enter the cell and

combine to form carbonic acid under the influence of enzyme carbonic anhydrase.

Bicarbonate is actively excreted at the basal side of the cell and is exchanged for chlorine.

Potassium is exchanged for hydrogen ions at the apical side of the cell.

Chlorine ions are also actively secreted.

The chief cells also secrete intrinsic factor, a substance essential for the absorption of vitamin B12 in the small intestine. In chronic gastritis, this may not be secreted, and the medical condition pernicious anemia will develop.

Bicarbonate Rich Mucous SecretionMucous secretion rich in alkaline bicarbonate

protects the stomach from the acid of the gastric juice.

Mechanism of mucous secretion Carbon dioxide and water enter the cell and

combine to form carbonic acid under the influence of the enzyme carbonic anhydrase.

Hydrogen ions are actively secreted on the basal side of the cell in exchange for sodium.

Bicarbonate ions are actively secreted on the apical or lumen side of the cell in exchange for chlorine.

Secretion and activation of PepsinogenPepsinogen is secreted by the peptic or

chief cells of the glandWhen first secreted pepsinogen is inactive,

but contact with acid converts it to the active form pepsin by splitting pepsinogen molecule. Pepsin functions best between 1.8 and 3.8

Stimulation of Gastric Acid secretionThe oxyntic cells function in close association

with histamine producing cells called enterochromaffin cells (ECL),which secrete histamine. These cells release histamine in direct contact with the oxyntic glands and promote the secretion of Hcl.

The activation of this complex is under hormonal (gastrin) and nervous control.

stimulating action

Gastrin, secreted by the G cells in the antrum of the stomach in response to the presence of proteins is the most potent stimulator of the Histamine /Acid complex.

The gastrin is not only carried by the blood directly into the lumens of gastric pits as a direct stimulating action.

The Histamine/Hcl complex is also activated by acetylcholine released by the vagus nerve.

Other substances also control Acid secreted, mainly through their action on Gastrin production

Inhibition of Gastric Acid secretion Factors which slow stomach emptying, which was

discussed when considering motility will also reduce gastrin production and hence Acid secretion

Regulation of pepsinogen Secretion Pepsinogen secretion occurs in response to two

signals;Acetylcholine release from the vagus nerve Stimulation of peptic cell secretion in response to

acid in the stomach, probably not directly but through the enteric nervous system.

Gastric Events Following Ingestion of a mealDigestion is traditionally divided into three

phases;Cephalic PhaseGastric Intestinal

The Cephalic PhaseSecretion of gastric juice is a continuous process. Secretion

of gastric juice by the stimuli arising from head region is called cephalic phase.

This phase of gastric secretion is under nervous control.During this phase, the gastric secretion occurs without the

presence of food in the stomach. The gastric juice secreted during this phase is called appetite

juice. The quantity of the juice is less but it is rich in enzymes and

hydrochloric acid.

Cephalic phase is regulated by the nervous mechanisms which operate through reflex action. Two types of reflexes occur;

UnconditionedConditioned

Unconditioned ReflexUnconditioned reflex is the inborn reflex. When

food is placed in the mouth, it induces salivary secretion. Simultaneously, gastric secretion also occurs.

Stages of the reflex action i. The presence of food in the mouth stimulates

the taste buds and other receptors in the mouth ii. The sensory ( afferent) impulses from mouth

pass via afferent nerve fibers of glossopharyngeal and facial nerves to the appetite center present in the amygdala of the hypothalamus.

iii. From here, the efferent impulses pass through dorsal nucleus of the vagus and vagal efferent nerve fibers to the wall of the stomach

iv. Acetylcholine is secreted at the vagal efferent nerve endings and stimulates gastric glands to increase the secretion.

Conditioned ReflexConditioned reflex is the reflex response acquired by

previous experience. Presence of food in the mouth is not necessary to elicit this reflex. By this reflex, the sight , smell, hearing or thought of food which induce salivary secretion induce gastric secretion also.

Stages of reflex action;i. Impulses from the special sensory organs (eye, ear,

and nose) pass through afferent fibers of neural circuits to the cerebral cortex

ii. Thinking of food stimulates the cerebral cortex (Integrating center) directly

iii. From cerebal cortex the impulses pass through dorsal nucleus of vagus and vagal effents and reach stomach wall.

iv. The vagal nerve endings secrete acetylcholine. It stimulates the gastric glands to increase its secretion.

The cephalic vagal reflex then causes the stomach to begin acid secretion.

The parasympathetic neurons innervate; Parietal Cells, which release gastric acidEnterochromaffin cells, which release

histamine that triggers gastric acid release G cells, which release hormone Gastrin. Gastrin in turn promotes acid release, both

directly and indirectly through histamine release.

By the time food reaches the stomach, the lumen has become acidified. When acid being secreted, mucosal bicarbonate secretion increases to protect the mucosa from autodigestion.

Gastric Phase The secretion of gastric juice when the food

enters the stomach is called gastric phase. It is under both nervous and hormonal control. The gastric juice secreted during this phase is rich in pepsinogen and hydrochloric acid.

The mechanisms involved in this phase are;1 Nervous mechanism through local

myenteric reflex and vagovagal reflex2 Hormonal mechanism through gastrin.

The stimuli, which initiate these mechanisms are;

1 Distention of the stomach2 Mechanical stimulation of gastric mucosa by

bulk of food3 Chemical stimulation of gastric mucosa by

food contents

1. Nervous MechanismLocal myenteric reflexLocal myenteric reflex is the reflex secretion of

gastric juice which is elicited by stimulation of myenteric nerve plexus in stomach wall. After entering stomach, the food particles stimulate the local nerve plexus present in the wall of the stomach. These nerve fibers release additional acetylcholine, which further stimulate the gastric glands to secrete a large quantity of gastric juice. Simultaneously, acetylcholine stimulates G cells to secrete gastrin

Vagovagal reflex( both afferent and efferent impuses pass through vagus)

Vagovagal reflex is the reflex in which entrance of food in the stomach causes secretion of gastric juice.

It involves both afferent and efferent vagal fibers.Presence of food in the stomach stimulates the sensory

(afferent) nerve endings of vagus which generates the sensory impulses.

The sensory impulses are transmitted to the brainstem via the sensory fibers of vagus.

Brain stem in turn sends efferent impules through the motor (efferent ) fibers of the vagus back to the stomach and cause secretion of gastric juice.

2. Hormonal Mechanism- GastrinGastrin is released when food enters the

stomach. The mechanism involved in the release of gastrin may be the local nervous reflex or vagovagal reflex.

The nerve endings release the neurotransmitter called gastrin releasing peptide which stimulates the G cells to secrete gastrin.

Gastrin stimulates the secretion of Hcl and pepsinogen by the gastric glands

Intestinal PhaseAs chyme enters the small intestine, the

intestinal phase begins. Some reflexes from this phase feed back to regulate gastric function, serving as a means by which the intestine influences the delivery of chyme from the stomach. Presence of acidic chyme in the duodenum inhibits gastric motility and secretion. These reflexes are mediated through the enteric nervous system and through various hormones.

Initial stage of intestinal phaseThe chyme entering the intestine stimulates

the duodenal mucosa to release gastrin which is transported to the stomach by the blood.

There (in the stomach) it increases gastric secretion.

Later stage of intestinal phase When food enters the intestine, after the

initial stage of increase in secretion of gastric juice, there is decrease or complete stoppage of secretion of gastric juice.

The gastric secretion is inhibited by 2 factors:1. Enterogastric reflex2. GI hormones

1. Enterogastric reflexIt is the reflex that inhibits the secretory motor

activities of the stomach due to the distention or chemical or osmotic irritation of intestinal mucosa.

It is mediated by myenteric nerve plexus of the enteric plexus and vagus.

2. GI hormones Presence of chyme in the intestine stimulates the

secretion of many GI hormones from the intestinal mucosa and other structures.

These hormones inhibit the gastric secretion. These hormones are;

SecretinCholecystokinin (CCK)Gastric inhibitory peptide (GIP)Vasoactive intestinal polypeptide (VIP)

The net result of all three phases of gastric function is the digestion of proteins in the stomach by pepsin, the formation of chyme by the action of acid and churning, and the controlled entry of chyme into the small intestine so that further digestion and absorption can take place.

FUNCTIONS OF STOMACH1. Mechanical functioni, Storage FunctionFood is stored in the stomach for a long period 3-4hrs

and emptied into the small intestine slowly. The maximum capacity of the stomach is up to 1.5 liters. This slow emptying of the stomach provides enough time

for proper digestion and absorption of food substances in the small intestine.

ii. Formation of chymeThe peritaltic movements of stomach mix gastric juice

and convert it into semisolid material known an chyme.

2.Digestive function 3. Protective4. Hemopoeitic5. ExcretoryMany substances like toxins, alkaloids and

metals are excreted through gastric juice.

Small IntestineThe upper small intestine secretes the

hormones cholecystokinin and secretin, mucous, intestinal digestive juices, and possibly enzymes. The small intestine secretes 1800mL daily. The pH7.5 to 8.0

Hormone SecretionCholecystokinin( CCK) is secreted in

response to fats and peptides in upper small intestines particularly the duodenum. Actions of CCK include;

Secretion of Pancreatic EnzymesContraction of GallbladderRelaxation of the sphincter of OddiIncreased tension in the pyloric sphincter,

inhibiting stomach emptying.

Secretin is released in response to the presence of Acid in the duodenum. Actions of secretin include;

Secretion of copious amounts of bicarbonate rich fluid by the biliary and gall bladder ducts

Secretion of alkaline rich mucous by the Brunners glands

Increased tension in the pyloric sphincter, inhibiting stomach emptying.

Brunner’s GlandsThe first few centimeters of the duodenum,

between the stomach and the ampulla of Vater, which contain numerous compound mucous glands called Brunner’s Glands. These secrete an alkaline rich mucous –pH between 8.0 and 8.9- in response to various stimuli;

Local irritation and the presence of acid Vagal stimulationGastrointestinal hormones especially secretin

Peptic ulcersGastric and duodenal ulcers are due mainly to the

breakdown of the protective barrier of alkaline mucous.The following factors have been identified as causes;Non Steroidal Anti- inflammatory DrugsThe bacteria Heliobacter Pylori.Excess acid secretion which can over whelm the

defenses. This can occur particularly in Zollinger- Ellison syndrome, caused by benign gastrin secreting tumors which may develop in the stomach or duodenum

It is of interest that Brunner Cell secretion is inhibited by sympathetic stimulation, thus this may be a connection between the hyper personality and their disposition to duodenal ulcers. Less mucous may be secreted making the duodenum more vulnerable to stomach acid and stomach pepsin.

Crypts of Lieberkuhn These are located over the entire surface of

the small intestine adjacent to the villi. They secrete a copious solution almost identical to interstitial fluid.

Mucous cellsThe villi are covered with goblet cells. About

a quarter to a half of the villi cells are mucous producing

Enzyme secretionSmall intestine secretions that are free of

cellular debris contains almost no enzymes! Thus the enzymes are either secluded within the cell or possibly they are attached to the brush border. In any case they are not flushed down the lumen and they remain local.

Regulation of the small intestine secretionsSecretions are produced almost entirely from

local enteric nervous reflexes in response to local stimuli.

PancreasThe pancreas is a large endocrine and

exocrine gland situated retroperitonealy beneath the stomach. The microscopic structure of the pancreas is similar to the salivary glands, the acini secretes enzymes, and the ductules and ducts secrete large quantities of a bicarbonate rich juice. These travel down the pancreatic duct to the second part of the duodenum where it exits via the Ampulla of Vater protected by the Sphincter of Oddi.

Enzymes secreted by the acini include proteolytic enzymes, amylases and lipases. The proteolytic enzymes are all secreted in an inactive form to prevent auto-digestion.

GROUP ENZYMES SUBSTRATES

Carbohydrates and starch

Amylase Starch

Fats Lipase and Colipase

Phospholipase cholesterol esterase

Trigycerides

Phospholipids Hydrolysis of Cholesterol esters

Proteins and Peptides Trypsin (Trypsinogen)

Chymotrypsin (Chymotrypsinogen)Carboxypolypeptidase

PeptidesPeptidesPeptides

Amylase breaks down carbohydrates (except Cellulose) to di-saccharides and some tri-saccharides.

Proteolytic enzymes are secreted in the inactive form to prevent auto digestion, they are converted to the active form in the small intestine. Trypsin is activated by enterokinase, secreted by the intestinal mucosa;

Trypsin then activates ChymotrypsinogenLipase converts fats to fatty acids and

monoglyceridesPhospholipase splits fatty acids from phospholipidsCholesterol esterase hydrolyses cholesterol esters.

Inhibition and Activation of EnzymesThe cells that secrete proteolytic enzymes

also secrete another substance called trypsin inhibitor. This prevents any trypsin that may form in the cells or ducts from becoming active, or activating the other enzymes. If however the pancreas becomes damaged or the pancreatic ducts become blocked then the action of trypsin inhibitor can be overwhelmed, and the very serious condition acute pancreatitis can develop. This can also occur if there is registration of intestinal contents through the Ampulla of Vater.

Secretion of Bicarbonate ionsCopious quantities of Bicarbonate ion rich

solutions are secreted by the ducts and ductules of the pancreas in response to the hormone Secretin.

Like gastric secretions, pancreatic secretions can be divided into three phases;

CephalicGastricIntestinal

Cephalic PhaseThe cephalic phase occurs when we think

about or anticipate food. It is mediated by the vagus nerve. It causes secretion of about 20% of the enzymes, but as this secretion is not accompanied by fluid secretions, the enzymes are not flushed out and tend to remain in the ducts .

Gastric phaseThis phase occurs when the food enters the

stomach, and again is mediated by neural stimuli. This accounts for another 5-10%, and again in the absence of serous flow these secretions tend to remain in the ducts

Intestinal phaseThis phase occurs when food enters the

small intestine and both serous pancreatic secretion becomes copious due to the hormone secretin.

Regulation of pancreatic SecretionThese basic stimuli control pancreatic

secretion; Nerves and Hormones1. Acetylcholine from the parasympathetic

nerves of the vagus and the cholinergic nerves of the enteric nervous system

2. Cholecystokinin secreted in the duodenum and the upper small intestine

3. Secretin, also secreted in the duodenum and upper jejunum

Acetylcholine and Cholecystokinin cause secretion of digestive enzymes, but these tend to remain in the gland, as there are no secretions to flow them out.

Secretin causes copious secretions of sodium bicarbonate rich fluids which wash the enzymes into the small intestines, and also neutralize the Hcl from the stomach.

Pancreatic enzymes work best between a pHof 7-8. Sodium bicarbonate has a pH of about 8

Biliary SystemAbout 1500 ml of bile daily. The bile is

secreted continuously by the hepatocytes of the liver, and if not immediately required for digestion are stored in the gall bladder. In the GB the bile is concentrated up to 15 times. Initially bile fluid has about the same electrolyte concentration of interstitial fluid, but during concentration large quantities of electrolytes( but not Ca++ ions) are reabsorbed.

In the presence of fats in the duodenum, CCK is secreted which causes strong contractions of the gall bladder and relaxation of the Sphincter of Oddi, propelling the bile into the small intestine. Vagal stimulation can have a similary but secondary effect.

Bile contains bile salts, an emulsifying agent necessary for the digestion and absorption of fats, as well as bilirubin, cholesterol and fatty acids

Composition of Human Hepatic Duct BileWater 97%Bile Salts 0.7%Bile Pigments 0.2%Cholesterol 0.07%Inorganic Salts 0.7%Fatty Acids 0.15%Fat 0.1%Lecithin 0.1%

Bile is continuously secreted by the hepatocytes. The fluid part of the secretion, a watery substance rich in sodium and bicarbonate is added by the ducts of the biliary system, and this secretion is stimulated by secretin.

Bile SaltsBile salts are the sodium and potassium salts of

bile acids., which are conjugated with glycine or taurine

Formation of Bile SaltsBile salts are formed from bile acids. There

are two primary bile acids in human, cholic acid and chenodeoxycholic acid which are formed in the liver and enter the intestine through bile. Due to the bacterial action in the intestine the primary bile salts are conjugated into secondary bile acids.

Cholic acid – deoxycholic acidChenodeoxycholic acid----- lithocholic acidSecondary bile acids from the intestine are

transported back to the liver through enterohepatic circulation. In the liver secondary bile acids are conjugated with glycine or taurin and form conjugated bile acids namely glycocholic acid and taurocholic acids. These bile acids combine with sodium or potassium to form the salts, sodium or potassium glycocholate and sodium or potassium taurocholate

Recycling of bile salts Enterohepatic circulation of bile saltsBile salts are recycled by the GI System.

About 95% of bile salts are reabsorbed from the terminal ileum and returned to the liver via the portal system. In addition, some salts are produced by bacterial action in the large intestine, and these too are returned to the liver.5% of the bile salts enter large intestines and they are converted into deoxycholate and lithocholate which is excreted in feces.

Recycling of bile salts Enterohepatic circulation of bile salts.cont….About 0.2 gm per day of bile salts are

manufactured by the liver, and the total pool of salts is about 3.5gm, so recycling occurs 6-8 times per day or about twice per meal. If compromised, and mal absorption of fat soluble vitamins can occur

Functions of bile saltsThey are the following: 1. Emulsification of FatsThis is the process by which the fat globules are

broken down into minute droplets and made in the form of milky emulsion. Fats are made into an emulsion in the small intestine by action of bile salts. Emulsification increases the surface area of these lipids making them much easier to digest. Un emulsified fat usually passes through the intestines and then it is eliminated in feces.

BILE SALTS Contnd..The lipolytic enzymes of the GI tract can not

digest the fats directly because the fats are insoluble in water due to the surface tension. The bile salts emulsify the fat by reducing the surface tension of the fats due to their detergent action. Because of the reduction in surface tension, the lipid granules are broken into minute particles which can be easily digested by lipolytic enzymes. The emulsification of fats by bile salts needs the presence of lecithin from bile.

2.Absorption of fatsBile salts help in the absorption of digested

fats from the intestine into blood. The bile salts combine with fats and make complexes of called micelles. The fats in the form of micelles can be absorbed easily

3. Choleretic ActionBile salts stimulate the secretion of bile from

liver. This action is called choleretic action.

4. Cholagogue ActionCholagogue is an agent, which increases the

release of bile from GB into the intestine by contraction of the GB. Bile salts act as cholagogues indirectly by stimulating the secretion of hormone CCK. This hormone causes contraction of GB resulting in release of bile

5.Laxative Laxative is an agent which induces

defecation. Bile salts act as laxatives by stimulating peristaltic movements of the intestine.

6. Preventing of Gallstone FormationBile salts prevent the formation of gall stones

by keeping the cholesterol and lecithin in solution. In the absence of bile salts, cholesterol precipitates along with lethicin and forms gallstone.

Bile pigmentsThese are the excretory products in the bile.

Bilirubin and biliverdin are the two bile pigments and bilirubin is the major bile pigment in humans.

The bile pigments are formed during the breakdown of hemoglobin, which is released from the destroyed RBCs in the reticuloendothelial system.

Formation and excretion of bile pigmentsStages of formation and circulation of bile

pigments1. The senile erythrocytes are destroyed in

reticuloendothelial system and the hemoglobin is released from hem.

2. The hemoglobin is broken into globin and heme3. Heme is split into iron and pigment biliverdin 4. The iron goes to iron pool and is reused5. The first formed pigment biliverdin is reduced

to bilirubin

Formation and excretion of bile pigments contnd6. The bilirubin is released into blood from

reticuloendothelial cells.7. In the blood, the bilirubin is transported by the

plasma protein, albumin. The bilirubin circulating in the blood is called free bilirubin.

8. Within few hours after entering the circulation, the free bilirubin is taken up by the liver cells.

9. In the liver, it is conjugated with glucuronic acid to form conjugated bilirubin

10. Conjugated bilirubin is then excreted into intestine through bile

Fate of conjugated bilirubinStages of excretion of conjugated bilirubin1. In the intestine 50% of the conjugated

bilirubin is converted to urobilinogen by intestinal bacteria. First the conjugated bilirubin is deconjugated into free bilirubin which is later reduced into urobilinogen.

2. Remaining 50% of the conjugated bilirubin from the intestine is absorbed into blood and enters the liver through portal vein( enterohepatic circulation). From liver, it is re excreted in bile.

Fate of conjugated bilirubin contnd.3. Most of the urobilinogen from the intestine

enters the liver via enterohepatic circulation. Later it is re-excreted through bile.

4. About 5% of the urobolinogen is excreted by kidney through urine. In urine , due to the exposure to air, the urobilinogen is converted into urobilin by oxidation.

5. Some of the urobilinogen is excreted in feces as stercobilinogen. In feces, stercobilinogen is oxidized to stercobilin

Functions of Bile1. Digestive 2. Absorbtive3. Excretory Bile pigments, Heavy metals copper and iron,

bacteria like typhoid bacteria, toxins, cholesterol, lecithin and alkaline phosphatase

4. Laxative5. Antiseptic action Bile inhibits the growth of certain bacteria in the

lumen of intestine by its natural detergent action

Functions of Bile contnd6. Choleretic action 7. Maintenance of pH in GI tractAs bile is highly alkaline, it neutralizes acid

chyme which enters the intestine from the stomach.

8. Prevention of gall stone formation9. Lubricates Mucin in bile acts as lubricant10. Cholagogue action

Regulation of Bile SecretionBile secretion is a continuous process though

the amount may be less during fasting. It increases three hours after meals. The secretion of bile from the liver and release of bile from the gallbladder are influenced by some chemical factors which are categorized into three groups:

1.Choleretics2.Cholagogue3.Hydrocholeretic agents

1. Choleretics Substances, which increase the

secretion of bile in the liver, are known as choleretics. The effective choleretic agents are :

1. Acetycholine2. Secretin3. Cholecystokinin4. Acid chyme in intestine5. Bile salts

CholagoguesCholagogue is an agent, which increases the release of

bile from gallbladder into the intestine. It does not influence the secretion of bile in the liver. The release of bile into intestine is achieved by causing contraction of gallbladder. The common cholagogues are;

1.Bile salts2.Calcium3.Fatty acids4.Amino acids5.Inorganic acidsAll these substances stimulate the secretion of

cholecytokinin, which in turn causes contraction of gallbladder and flow of bile into intestine.

Hydrocholeretic AgentsHydrocholeretic agent is a substance which causes secretion of bile from liver with large amount of water and less amount of solids. Hydrochloric acid is a hydrocholeretic agent.

JAUNDICE OR ICTERUS Jaundice or icterus is the condition characterized by yellow

coloration of the skin, mucous membrane and deeper tissues due to the increased bilirubin level in the blood. The word jaundice is derived from the French word “jaune” meaning yellow.

The normal serum bilirubin level 0.5-1.5 mg/dL. Jaundice occurs when biliburin level exceeds 2mg/dL.

TYPES OF JAUNDICE Jaundice is classified into three types:1. Prehepatic or hemolytic jaundice2. Hepatic or hepatocellular jaundice3. Posthepatic or obstructive jaundice

1.Prehepatic or hemolytic Jaundice.Hemolytic jaundice is the type of jaundice

that occurs because of excessive destruction of RBCs resulting in increased blood level of free (unconjugated) biliburin. In this condition the function of the liver is normal. But the quantity of biliburin increases enomously. The liver cells cannot excrete that much biliburin rapidly. So, it accumulates in the blood resulting in jaundice.

Formation of urobilinogen also increases resulting in the excretion of more amount to urobilinogen in urine.

CAUSES Any condition that causes hemolytic anemia can lead

to hemolytic jaundice. The common causes of hemolytic jaundice are:

1.Liver failure2.Renal disorder3.Hypersplenism4.Burns5.Infections such as malaria 6.Hemoglobin abnormalities such as sickle cell

anemia or thalassemia7.Drugs or chemical substances causing red cell

damage8.Autoimmune diseases

2. Hepatic or Hepatocellular or Cholestatic Jaundice

This is the type of jaundice that occurs due to the damage of hepatic cells. Because of the damage, the conjugated biribulin from liver cannot be excreted and it returns to blood.

Causes 1.Infection (infective jaundice) by virus

resulting in hepatitis (viral hepatitis)2.Alcoholic Hepatitis3.Cirrhosis of liver4.Exposure to toxic materials

3. Posthepatic or Obstructive or Extrahepatic Jaundice

This type of jaundice occurs because of the obstruction of bile flow at any level of the biliary system. The bile cannot be excreted into small intestine. So, bile salts and bile pigments enter the circulation. The blood contains more amount of conjugated bilirubin

COLONIC SECRETIONSThe chief function of the large intestine is

absorption of fluids and formation of feces. About 1-2 liters of fluid enter the large intestine, and these are mainly absorbed, only about 200ml being egested daily. The large intestine secretes about 200ml of fluid a day, mainly in the form of mucous.

DiarrheaThe large intestine can produce large

quantities of water and electrolytes in response to irritation, such as occurs in infections. This can lead to dehydration, but also has the beneficial effect of flushing out the irritants.

Digestion and Absorption OverviewDigestion of food breaks the large molecules

into smaller molecules suitable for absorbing in the small intestine. This takes place either both in the lumen of the canal in the chyme and at the epithelial junction of the cells of the small intestine.

The surface area for absorption is greatly increased by the christal folds and the villi of the small intestine , and the microvilli of the epithelial cells themselves, which form the brush border.

Digestion and Absorption overview contndSmall intestinal enzymes are anchored in the

apical margin of the epithelial cell, in the brush border. This prevents them from being washed down stream with the chyme.

The enterocyte is specialized for absorption of food stuffs, it is divided into an apical or luminal surface where the final digestion and absorption takes place, and a basal/lateral surface where the products of digestion are passed into the interstitial fluid. The transport mechanisms at these two surfaces are quite different.

Digestion and absorption overview contndThe apical surface is characterized by

numerous microvilli which greatly increase the surface area available for absorption. Adjacent to this is an unstirred layer of mucous that the products of digestion must penetrate before being absorbed.

The junctions between the cells is very tight, and no leakage takes place. At the walls of the base of the cells there is a space continuous with the interstitial space.

The enzymes of the small intestine consist of several peptidases; several enzymes for splitting disaccharides into monosaccharides and a lipase. These enzymes operate while the substrates are being absorbed through the epitheium.

Carbohydrate DigestionCarbohydrates are digested by salivary and

pancreatic enzymes (α-amylases) and by numerous oligosaccharidases of the small intestinal wall.

TABLES…

Carbohydrate Digestion contndThe amylase of the salivary gland (Ptyalin) is

inactivated by stomach acid, but when food enters the stomach it is first stored in the fundus of the stomach and not mixed with acid, so ptyalin can carry on acting until mixing with stomach acid takes place, which can be sometime. By some estimates up to a third of the carbohydrates are reduced to polysaccharides by the time chyme leaves the stomach. The other two thirds are digested by pancreatic amylase.

Carbohydrate Digestion ContndCarbohydrates are taken in mainly in the form of plant

carbohydrate (amylose) and animal carbohydrate (glycogen) together with some sugars, mainly disaccharides.

Both the parotid and pancreatic amylases hydrolyse the 1:4 link, but not the terminal 1:4 links or the 1:6 links. This breaks amylose down into disaccharides, and glycose with its 1:6 linkages into polysaccharides.

The net result of these actions are numerous disaccharides and polysaccharides. These are broken down into monosaccharides by enzymes attached to the enterocytes of the small intestine.

Carbohydrate Absorption Glucose is transported from the lumen into the

cell by a sodium linked co-transporter or symport (SGLT) and is thus highly dependent on the concentration of sodium in the lumen. Galactose uses the same mechanism.

Fructose uses a different mechanism, a facilitated carrier and is sodium independent.

Glucose is carried across the baso-lateral membrane by a facilitated carrier

Sugars are absorbed in the capillaries and carried to the liver.

Protein DigestionProtein and polypeptides are digested by

hydrolysis of the C-N bond.Proteolytic enzymes are all secreted in an

inactive form, to prevent auto-digestion, and are activated in the lumen of the gut: by HCl in the case of the stomach pepsinogen; by the enteropeptidase and trypin in the case of the pancreatic enzymes.

Protein Digestion contnndThe enzymes are divided into endo and exo-

peptidases. The endopeptidases cleave the polypeptide at the interior peptide bonds, the exopeptidases cleave the terminal amino acid. Exopeptidases are further subclassified into amino peptidases which cleave off the terminal amino acid at the amine end of the chain, and carboxypeptidases which cleave off the terminal amino acid at the carboxyl end of the chain.

Protein Digestion contnndStomach pepsin cleaves interior bond of

amino acids, and is particularly important for its ability to digest collagen. This is a major constituent of connective tissue of meat. In the absence of stomach pepsin, digestion in the small intestine proceeds with difficult. Stomach pepsin digests about 20% of the proteins, the rest is digested by pancreatic and small intestine enzymes.

TABLE…..

Protein AbsorptionSeveral different transport systems transport

amino acids into the enterocyte, each dealing with different groups of amino acids. Most of these are sodium dependent co- transporters. Di-peptides and tri-peptides are transported by a H+ ion dependent co –transporter. In the cell the poly- peptides may be reduced to amino acids, or they may be carried across the cell intact.

They are transported across the baso-lateral border by both co-transporters and facilitated transporters.

Protein Absorption cont..Some large peptides or proteins can be carried

across the cell by transcytosis., this is particularly true in small children, and is a mechanism whereby the immunoglobulins in the mother’s milk can be transferred to the child.

The enterocytes that do this are probably situated in the Crypts of Lieberkuhn, in infants the openings to the pits are much larger than in older children and adults

This mechanism also operates , but a lesser extent in adults.

Fats and Cholesterol DigestionFats are digested by lipases which hydrolyze the

glycerol- fatty acid bonds. Of particular importance in fat digestion and absorption are bile salts which emulsify the fats allowing for their solution as micelles in chyme, and increasing the surface area on which the pancreatic lipases can operate. Lipases are found in the mouth; stomach and the pancreas. Lingual lipase is inactivated by the acid of the stomach, it has an effect on the bolus in the fundus of the stomach before it is mixed with acid, as much as 30% of the fats are digested by this lipase.

Fats and Cholesterol Digestion Cont…Gastric lipase is of little importance in humans.

Pancreatic lipase accounts for the majority of fat digestion, and operates in conjunction with the bile salts

Bile salts have hydrophobic and hydrophilic side. These will attach to fat globules, emulsifying them to form micelles. Micelles are small and because they have hydrophilic side externally, they effectively allow the fats to acts like water soluble particles. This allows them to penetrate the unstirred layer adjacent to the small intestine epithelium, and to be absorbed.

Fat and Cholesterol digestion cont…In the absence of bile salts very few fatty

acids make it through this layer and much of the fat will pass through the gut unabsorbed causing steatorrhea(fatty stool)

Fats and Cholesterol AbsorptionThe micelles enable the fatty acids and the cholesterol

to cross the unstirred layer and come in contact with the brush border, where they easily cross the fat-soluble cell membrane. A smaller free fatty acids transfuse across the cell and out at the baso-lateral border, passing into the capillaries. However most fatty acids enter the smooth endoplasmic reticulum where they are repackaged into cholemicrons. These are carried out of the cell by exocytosis. The cholemicrons do not enter the capillaries, but pass instead into the lymphatic system where they carried to the thoracic duct. The thoracic duct empties into the superior venacava.

Nucleic AcidsRNA and DNA are broken down by

pancreatic enzymes in the intestinal mucosa. The nucleic bases are absorbed by active transport, the pentoses are absorbed with the other sugars.

Vitamins and MineralsVitaminsThe fat soluble vitamins A, D, and E are

absorbed in the upper small intestine. The factors that cause malabsorption of fat can affect absorption of these vitamins. Vitamin B12 is absorbed in the ileum and requires to be bound to Intrinsic factor, a protein secreted in the stomach, to be absorbed. If intrinsic factor is missing then Vitamin B12 is not absorbed and pernicious anemia results.

Vitamins and minerals cont…Of the water soluble vitamins, transport of

folate and B12 across the apical membrane are Na+ independent, but the other water soluble vitamins are absorbed by Na+ co- transporters.

CalciumBetween 30 and 80% of the bodies calcium

intake is absorbed. The rate of absorption is dependent on Ca++ needs.

Iron Almost all iron absorption occurs in the ferrous (Fe2+)

form in the duodenum. The ferric (Fe3+) form is converted to ferrous by an enzyme ferric reductase. A protein transporter designated DMTI is responsible for the absorption at the apical surface of the enterocyte. Heme molecules are transported by the HT protein transporter. At the basal lateral part of the enterocyte Ferrous ions are transported into the interstitial fluid by a transporter called ferroportin (FP)

In the plasma the ferrous form is reconverted back to the ferric form, and bound to an iron transporting protein Transferrin(TF)

Water and ElectrolytesThe small intestine is presented with 9 liters, 2

extrinsic, and 7 intrinsic, of fluid a day for reabsorption. In health all but 200ml of fluid leave the small intestine and enter the colon.

In the small intestine water is absorbed via the osmotic effects of nutrient absorption. The osmotic gradient is established across the intestinal epithelium that simultaneously drives the movement of water across tight junctions. The mechanism for nutrient driven Na+ and water

Water and ElectrolytesThe junctions between epithelial cells in the large

intestine are much tighter than in the small intestine, and this precludes leakage of sodium into the lumen. Most of the fluid and electrolytes are absorbed in the descending colon.

Although proteins and sugars have usually all been absorbed by the time fluid reaches the large intestine, the colon is capable for absorbing these substrates. Some hard to digest substances, such as beans, can be digested by colonic bacteria, and these bacteria can digest small amounts of cellulose.