The Digestive System

Digestive Process

Figure 23.2

GI TractExternal environment for the digestive

processRegulation of digestion involves:

Mechanical and chemical stimuli – stretch receptors, osmolarity, and presence of substrate in the lumen

Extrinsic control by CNS centersIntrinsic control by local centers

Receptors of the GI TractMechano- and chemoreceptors respond to:

Stretch, osmolarity, and pHPresence of substrate, and end products of

digestionThey initiate reflexes that:

Activate or inhibit digestive glands Mix lumen contents and move them along

Nervous Control of the GI TractIntrinsic controls

Nerve plexuses near the GI tract initiate short reflexes

Short reflexes are mediated by local enteric plexuses (gut brain)

Extrinsic controlsLong reflexes arising within or outside the GI

tract Involve CNS centers and extrinsic autonomic

nerves

Nervous Control of the GI Tract

Figure 23.4

Secretions of the StomachChyme: ingested food plus stomach secretionsMucus: surface and neck mucous cells

Viscous and alkalineProtects from acidic chyme and enzyme pepsinIrritation of stomach mucosa causes greater mucus

Intrinsic factor: parietal cells. Binds with vitamin B12 and helps it to be absorbed. B12 necessary for DNA synthesis

HCl: parietal cellsKills bacteriaStops carbohydrate digestion by inactivating salivary

amylaseDenatures proteinsHelps convert pepsinogen to pepsin

Pepsinogen: chief cells. Packaged in zymogen granules released by exocytosis. Pepsin catalyzes breaking of covalent bonds in proteins.

G-cells: secrete the hormone gastrin which stimulates HCl secretion from parietal cells

Hydrochloric Acid Production1. CO2 and Cl- diffuse from the blood into the stomach cell.2. CO2 combines with H2O to form H2CO3.

3. H2CO3 dissociates into bicarbonate (HCO3-) and H+.4. H+ combines with Cl- in duct of gastric gland to form HCl-.5. An ATP pump is necessary to pump the HCl- into the duct since the concentration of HCl- is about a million times more concentrated in the duct than in the cytosol of the cell.

Regulation of Gastric SecretionNeural and hormonal mechanisms

regulate the release of gastric juiceStimulatory and inhibitory events occur in

three phasesCephalic (reflex) phase: prior to food entryGastric phase: once food enters the stomachIntestinal phase: as partially digested food

enters the duodenum

Release of Gastric Juice

Figure 23.16

Cephalic PhaseThe taste or smell of food,

tactile sensations of food in the mouth, or even thoughts of food stimulate the medulla oblongata.

Parasympathetic action potentials are carried by the vagus nerves to the stomach.

Preganglionic parasympathetic vagus nerve fibers stimulate postganglionic neurons in the enteric plexus of the stomach.

Postganglionic neurons stimulate secretion by parietal and chief cells (HCl and pepsin) and stimulate the secretion of the hormone gastrin.

Gastrin is carried through the circulation back to the stomach where it stimulates further secretion of HCl and pepsin.

Gastric PhaseDistention of the stomach

activates a parasympathetic reflex. Action potentials are carried by the vagus nerves to the medulla oblongata.

Medulla oblongata stimulates further secretions of the stomach.

Distention also stimulates local reflexes that amplify stomach secretions.

Intestinal Phase Chyme in the duodenum with

a pH less than 2 or containing lipids inhibits gastric secretions by three mechanisms

1. Sensory input to the medulla from the duodenum inhibits the motor input from the medulla to the stomach. Stops secretion of pepsin and HCl.

2. Local reflexes inhibit gastric secretion

3. Secretin, gastric inhibitory polypeptide, and cholecystokinin produced by the duodenum inhibit gastric secretions in the stomach.

Regulation of Gastric EmptyingGastric emptying is regulated by:

The neural enterogastric reflexHormonal (enterogastrone) mechanisms

These mechanisms inhibit gastric secretion and duodenal filling

Carbohydrate-rich chyme quickly moves through the duodenum

Fat-laden chyme is digested more slowly causing food to remain in the stomach longer

Regulation of Gastric Emptying

Figure 23.19

Microscopic Anatomy of the Liver

Figure 23.24c, d

Histology of the Liver

Connective tissue septa branch from the porta into the interior Divides liver into lobules Nerves, vessels and ducts follow

the septa Lobules: portal triad at each

corner Three vessels: hepatic portal

vein, hepatic artery, bile duct (hepatic duct in diagram)

Central vein in center of lobule Central veins unite to form

hepatic veins that exit liver and empty into inferior vena cava

Hepatic cords: radiate out from central vein. Composed of hepatocytes

Hepatic sinusoids: between cords, lined with endothelial cells and hepatic phagocytic (Kupffer) cells

Bile canaliculus: between cells within cords

Functions of the LiverBile production: 600-1000 mL/day. Bile salts (bilirubin),

cholesterol, fats, fat-soluble hormones, lecithinNeutralizes and dilutes stomach acidBile salts emulsify fats. Most are reabsorbed in the ileum.Secretin (from the duodenum) stimulates bile secretions,

increasing water and bicarbonate ion content of the bileStorage

Glycogen, fat, vitamins, copper and iron. Hepatic portal blood comes to liver from small intestine.

Nutrient interconversionAmino acids to energy producing compoundsHydroxylation of vitamin D. Vitamin D then travels to kidney

where it is hydroxylated again into its active formDetoxification

Hepatocytes remove ammonia and convert to ureaPhagocytosis

Kupffer cells phagocytize worn-out and dying red and white blood cells, some bacteria

SynthesisAlbumins, fibrinogen, globulins, heparin, clotting factors

Composition of BileA yellow-green, alkaline solution

containing bile salts, bile pigments, cholesterol, neutral fats, phospholipids, and electrolytes

Bile salts are cholesterol derivatives that:Emulsify fatFacilitate fat and cholesterol absorptionHelp solubilize cholesterol

Enterohepatic circulation recycles bile salts

The chief bile pigment is bilirubin, a waste product of heme

Regulation of Bile Release

Figure 23.25

Blood and Bile Flow Through the Liver

Pancreas Pancreas both endocrine and

exocrine Head, body and tail Endocrine: pancreatic islets.

Produce insulin, glucose, and somatostatin

Exocrine: groups acini (grape-like cluster) form lobules separated by septa.

Intercalated ducts lead to intralobular ducts lead to interlobular ducts lead to the pancreatic duct.

Pancreatic duct joins common bile duct and enters duodenum at the hepatopancreatic ampulla controlled by the hepatopancreatic ampullar sphincter

Pancreatic Secretions: Pancreatic JuiceAqueous. Produced by columnar epithelium lining smaller ducts. Na+,

K+, HCO3-, water. Bicarbonate lowers pH inhibiting pepsin and

providing proper pH for enzymesEnzymatic portion:

TrypsinogenChymotrypsinogenProcarboxypeptidasePancreatic amylasePancreatic lipasesDeoxyribonucleases and ribonucleases

Interaction of duodenal and pancreatic enzymes.Enterokinase from the duodenal mucosa and attached to the

brush border activates trypsinogen to trypsin. Trypsin activates chymotrypsinogen to chymotrypsinTrypsin activates procarboxypeptidase to carboxypeptidase.

Trypsin, chymotrypsin and carboxypeptidase digest proteins: proteolytic.

Pancreatic amylase continues digestion of starchPancreatic lipase digests lipidsDeoxyribonucleases and ribonucleases digest DNA and ribonucleic

acid, respectively

Bicarbonate Ion Production in Pancreas

Regulation of Pancreatic Secretion

Figure 23.28

Secretions of Large IntestineMucus provides protection

Parasympathetic stimulation increases rate of goblet cell secretion

Pumps: bacteria produce acid and the following remove acid from the epithelial cells that line the large intestineExchange of bicarbonate ions for chloride ionsExchange of sodium ions for hydrogen ions

Bacterial actions produce gases (flatus) from particular kinds of carbohydrates found in legumes and in artificial sugars like sorbitol

Bacteria produce vitamin K which is then absorbed

Feces consists of water, undigested food (cellulose), microorganisms, sloughed-off epithelial cells

Digestion, Absorption, Transport

Digestion Breakdown of food molecules for absorption

into circulation Mechanical: breaks large food particles to small Chemical: breaking of covalent bonds by digestive

enzymes

Absorption and transportMolecules are moved out of digestive tract

and into circulation for distribution throughout body

Carbohydrates: Hydrolyzed into Monosaccharides

Glucose is transported to cells requiring energy; insulin influences rate of transport

Lipids Include triglycerides, phospholipids,

steroids, fat-soluble vitamins Bile salts surround fatty acid and glycerol

to form micelles Chylomicrons are 90% triglyceride, 5%

cholesterol, 4% phospholipid, 1% protein. Chylomicrons enter blood stream and

travel to adipose tissue. In blood, triglycerides converted back into fatty acids and glycerol where they are transported into the adipose cells, then converted back into triglycerides.

Transport of Lipids Across Intestinal Epithelium

Fatty Acid Absorption

Figure 23.36

Lipoproteins All lipids carried in the blood are done

so in combination with protein to make them soluble in plasma.

Cholesterol: 15% ingested; 85% manufactured in liver and intestinal mucosa

Lipids are lower density than water; proteins are higher density than water

Chylomicrons: 99% lipid and 1% protein (extremely low density); enter lymph

VLDL: 92% lipid, 8% protein Form in which lipids leave the liver Triglycerides removed from VLDL

and stored in adipose cells. VLDL has been converted to LDL.

LDL: 75% lipid, 25% protein Transports cholesterol to cells Cells have LDL receptors # of LDL receptors become less

once cell’s lipid/cholesterol needs are met.

HDL: 55% lipid, 45% protein Transports excess cholesterol from

cells to liver

Transport of LDL into Cells

ProteinsPepsin breaks proteins into smaller

polypeptide chainsProteolytic enzymes produce small peptide

chainsDipeptides, tripeptides, amino acids

After absorption, amino acids are are carried through the hepatic portal vein to the liver.

Amino Acid Transport

Chemical Digestion: Nucleic AcidsAbsorption: active transport via membrane

carriersAbsorbed in villi and transported to liver via

hepatic portal veinEnzymes used: pancreatic ribonucleases and

deoxyribonuclease in the small intestines

Electrolyte AbsorptionMost ions are actively absorbed along the

length of small intestine Na+ is coupled with absorption of glucose and

amino acidsIonic iron is transported into mucosal cells where

it binds to ferritinAnions passively follow the electrical

potential established by Na+

K+ diffuses across the intestinal mucosa in response to osmotic gradients

Ca2+ absorption:Is related to blood levels of ionic calciumIs regulated by vitamin D and parathyroid

hormone (PTH)

Water Absorption95% of water is absorbed in the small

intestines by osmosisWater moves in both directions across

intestinal mucosaNet osmosis occurs whenever a

concentration gradient is established by active transport of solutes into the mucosal cells

Water uptake is coupled with solute uptake, and as water moves into mucosal cells, substances follow along their concentration gradients

Water and Ions

Water: can move in either direction across wall of small intestine depending on osmotic gradients

Ions: sodium, potassium, calcium, magnesium, phosphate are actively transported

Introduction to Introduction to Gastrointestinal Gastrointestinal

PhysiologyPhysiology

Gastrointestinal System(GIS)Gastrointestinal System(GIS)The main function of the GIS is to process

ingested food into molecular forms that are transferred, with salts and water to the body’s internal environment where the circulatory system can distribute them to cells.

This system includes the Gastrointestinal Tract (GI) which is made up of; mouth, pharynx, oesophagus, stomach, small intestine, large intestine and accessory organs.

The accessory organs include; salivary glands, liver, gall bladder and pancreas

Organ Exocrine secretions

Digestion Absorption

Bulk transport/ Function

Mouth and PharynxSalivary glands

Salt and waterMucusAmylase

Chewing breaks down food particlesAmylase partially digests polysaccharides

No Moistens and lubricates food particles

Oesophagus Mucus No No Moves food to stomach by peristaltic wavesProvides lubrication

Stomach HClPepsinsMucus

Solubilises food particles, kills microbes, activates pepsinogens to pepsinPepsins break down protein

No Store food particlesRegulate rate at which contents are emptied into the small intestine

Pancreas EnzymesBicarbonate

CarbohydratesFatsProteins and Nucleic acids

No Neutralize HCl entering the small intestine

Organ Exocrine secretions

Digestion Absorption Bulk transport/ Function

Liver Bile SaltsBicarbonateOrganic waste products and trace metals

Solubilizes water insoluble fats

No Neutralizes HCl entering the small intestineElimination of feces

Gall Bladder No No No Stores and concentrates bile between meals

Small Intestine

EnzymesSalt and waterMucus

Hydrolytic enzymes break down carbohydrates, fats and proteins into monosaccharides, fatty acids, amino acids

Monosaccharides, fatty acids, amino acids, vitamins, minerals, water

Maintain fluidity of luminal contentsLubrication

Large Intestine

Mucus No Salt, water Storage and concentration of undigested matterMixing and propulsion of contentsDefecationLubrication

Structure of the GI Tract WallStructure of the GI Tract WallThe wall of the gastrointestinal tract has

the same general structure from mid-oesophagus to the anus.

The wall comprises: - mucosa, -submucosa, -muscularis externa - serosa.

Walls of the GI TractIn the small intestine finger like projections

called villi which extend from the luminal surface. The centre of each villus is occupied both by lacteal (single blind-ended lymphatic vessel) and a capillary network.

The surface of each villus is covered with a layer of epithelial cells whose surface membrane form projections called microvilli

Epithelial FunctionThe increased surface area of the wall in the

small intestine by villi and microvill allow for mass absorption.

The invaginatons in the wall form exocrine glands and allow passage of substances.

They also have a paracrine function which refers to the ability of the endocrine cells within the epithelial layer to release hormones and bind to the receptors of nearby cells to affect their function.

Epithelia Lifetime

17 Billion epithelial cells are replaced each day.

The entire epithelium of the small intestine is replaced approximately every five days.

The rapid cell turnover makes the lining of the intestinal tract suseptible to damage by agents that inhibit cell division (e.g. anticancer drugs)

Digestion & Absorption ObjectivesDigestion & Absorption ObjectivesDescribe the process involved in the breakdown and

absorption of ingested carbohydrates.

Describe fat absorption, resynthesis of triglycerides and phospholipids, the formation of chylomicrons and the absorption into the lacteals.

Describe the absorptive mechanisms involved in protein absorption.

Describe the absorption mechanisms for the different water- and fat soluble vitamins, noting the special role of intrinsic factor in the absorption of vitamin B 12.

Describe the epithelial processes involved in the active absorption of water and minerals.

Digestion and Absorption Digestion and Absorption Overview of the four basic digestive processes:

Digestion: dissolving and breaking down process of food into small molecules.

Absorption: the process whereby molecules produced from digestion moves from the GI tract across a layer of epithelial cells and enters the blood.

Secretion: The release of substances that aid in digestion.( HCL acid, bile and digestive enzymes)

Motility: Contraction of the GI tract .

Digestion and Absorption Digestion and Absorption Carbohydrates:

Digestion and Absorption Digestion and Absorption Carbohydrates

Digestion and AbsorptionDigestion and AbsorptionGlucose & Galactose enter epithelial cells via sodium-linked secondary active transport across the epithelial membrane.

Fructose enters by facilitated diffusion.

These monosaccharides exit via the Basolateral Membrane by facilitated diffusion transporters and then diffuse into the capillaries.

Digestion and AbsorptionDigestion and AbsorptionProteins Proteins need to be broken down into smaller molecules

(amino acids, dipeptides & tripeptides) before they can be absorbed by the small intestine.

Proteases involved in this process are : -Pepsin: secreted as pepsinogen into the stomach -Trypsin: secreted as trypsinogen into small intestine.

-Chymotrypsin: secreted as chymotrypsinogen, into small intestine.

-Carboxypeptidase: secreted as procarboxypeptidase into small intestine. -Aminopeptidase (brush border enzyme) is also used.

Digestion and AbsorptionDigestion and Absorption

Digestion and AbsorptionDigestion and Absorption

Digestion and AbsorptionDigestion and AbsorptionFree Amino acids enter

absorptive epithelial cells via sodium-linked secondary active transport across the apical membrane.

Others are transported via facilitated diffusion into cells.

Dipeptides and Tripeptides are actively transported across the apical membrane and then broken down to amino acids within the cell.

Amino acids from the cell enter the capillaries via facilitated diffusion across the basolateral membrane.

Digestion and AbsorptionDigestion and AbsorptionFats Fats are ingested in the form of Triglycerides.Fat digestion occurs almost entirely in the small

intestine whereby lipase splits bonds linking fatty acids to the first and third carbon atoms of glycerol. Two fatty acids and a monoglyceride are produced.

Ingested fats aggregate into large lipid droplets in the upper portion of the stomach. (insolubility in water).

Emulsification: breakdown of large lipid droplets into smaller droplets resulting in an increased rate of digestion.

Digestion and AbsorptionDigestion and AbsorptionFats

Digestion and AbsorptionDigestion and Absorption ‘Mechanical disruption of fat

globlets’ (contractions of stomach and small intestine) & ‘ An emulsifying agent’ (Phospholipids in food and secreted bile salts) is needed for the emulsification of fat.

Non polar regions on phospholipids and bile salts associate with the non polar interior of the lipid droplets.

Repulsion of other lipid droplets occurs preventing reaggregation.

Although accessibility to lipase is impaired, colipase (secreted from pancreas) binds lipase onto the surface of the lipid droplet.

Digestion and AbsorptionDigestion and AbsorptionMicelles: similar in structure to

emulsion droplets & comprise clusters of bile salts, fatty acids, monoglycerides & phospholipids. (Polar ends oriented toward micelle surface; nonpolar portions form micelle’s core).

Micelles continuously breakdown & reform which increases absorption.

Broken-down micelles release its contents (fatty acids and monoglycerides) which diffuse into epithelial cells.

Fatty acids and monoglycerides enter the intestinal lumen and triglycerides are released into the interstitial fluid.

Re-synthesis of triglycerides occurs on the smooth E.R. within epithelial cells.

Digestion and AbsorptionDigestion and Absorption Chylomicrons: extracellular fat droplets containing triglycerides and other lipids (phospholipids, cholesterol & fat-soluble vitamins) which have been absorbed in the absorption process.

Chylomicrons released from epithelial cells enter lacteals and then into the lymph.

A basement membrane(extracellular glycoprotein layer) prevents entry of chylomicrons into the capillaries.

Digestion and AbsorptionDigestion and Absorption

Digestion and AbsorptionDigestion and AbsorptionWater & Minerals:Small amounts of water are absorbed in the stomach in spite

of the absence of solute absorbing mechanisms.

Significant absorption takes places in the epithelial membranes of the small intestine.

A water concentration difference is required for net water diffusion and this is established via active absorption of solutes.( active transport of sodium across epithelium)

Water moves by osmosis across the epithelium.

Iron absorption

Increased iron deposition leads to hemochromatosis.

Mouth Food enters the

digestive tract through the mouth.

As food enters the mouth, breakdown begins:

Mechanical breakdown by chewing (teeth) and actions of the tongue.

Chemical breakdown of starch by production of salivary amylase from the salivary glands.

SalivaSaliva

Salivary amylase hydrolyzes internal α1-4 bonds within starch.

A second digestive enzyme, lingual lipase, is produced by lingual serous glands on the tongue and in the back of the mouth.

This enzyme hydrolyzes dietary triacylglycerols (triglycerides) in the stomach.

Mucus secretions found in saliva contain glycoproteins.

Mucus lubricates food and coats and protects the oral mucosa.

The secretion of saliva is controlled by both sympathetic and parasympathetic neurons.

There is no hormonal regulation of salivary secretion.

In the absence of ingested material, a low rate of salivary secretion keeps the mouth moist.

In the presence of food, salivary secretion increases markedly.

This reflex response is initiated by chemoreceptors (acidic fruit juices are a particularly strong stimulus) and pressure receptors in the walls of the mouth and on the tongue.

Increased secretion of saliva is accomplished by a large increase in blood flow to the salivary glands, which is mediated by both neural activity and paracrine/autocrine agents released by the active cells in the salivary gland.

The volume of saliva secreted per gram of tissue is the largest secretion of any of the body’s exocrine glands.

SwallowingSwallowing Swallowing is a complex reflex initiated when

pressure receptors in the walls of the pharynx are stimulated by food or drink forced into the rear of the mouth by the tongue.

These receptors send afferent impulses to the swallowing center in the brainstem medulla oblongata.

This center then elicits swallowing via efferent fibers to the muscles in the pharynx and esophagus as well as to the respiratory muscles.

Samantha

food going down the wrong hole

Swallowing is an example of a reflex in which multiple responses occur in a temporal sequence determined by the pattern of synaptic connections between neurons in a brain coordinating center.

Since both skeletal and smooth muscles are involved, the swallowing center must direct efferent activity in both somatic nerves (to skeletal muscle) and autonomic nerves (to smooth muscle).

Simultaneously, afferent fibers from receptors in the esophageal wall send information to the swallowing center that can alter the efferent activity.

PharynxPharynx Swallowing moves ingested material (bolus) from the mouth into the

pharynx.

The pharynx is 14-16cm long.

As the ingested material (bolus) moves into the pharynx, the soft palate elevates and lodges against the back wall of the pharynx.

This prevents food from entering the nasal cavity.

Impulses from the swallowing center inhibit respiration, raise the larynx, and close the glottis (the area around the vocal cords and the space between them).

This keeps food from moving into the trachea.

As the tongue forces the food farther back into the pharynx, the food tilts a flap of tissue, the epiglottis, backward to cover the closed glottis, thereby preventing food from entering the trachea.

PharynxPharynx

The pharynx is divided into three sections:

the nasopharynx

the oropharynx

the laryngopharynx

How the Esophagus Works….How the Esophagus Works…. As a person swallows, food

moves from the mouth to the throat, also called the pharynx (1).

The upper esophageal sphincter opens (2) so that food can enter the esophagus,

where waves of muscular contractions, called peristalsis, propel the food downward (3).

The food then passes through the lower esophageal sphincter (4)

and moves into the stomach (5).

“Food goin’ down d wrong hole”

http://kidshealth.org/kid/watch/er/choking.html

Once in the esophagus, the food is moved toward the stomach by a progressive wave of muscle contractions that proceeds along the esophagus, compressing the lumen and forcing the food ahead of it.

Such waves of contraction

in the muscle layers surrounding a tube are known as peristaltic waves.

One esophageal peristaltic wave takes about 9 s to reach the stomach.

Upper Esophageal Sphincter

Lower Esophageal Sphincter

The esophageal phase of swallowing begins with relaxation of the upper esophageal sphincter.

Immediately after the food has passed, the sphincter closes, the glottis opens, and breathing resumes.

The lower esophageal sphincter opens and remains relaxed throughout the period of swallowing, allowing the arriving food to enter the stomach.

After the food has passed, the sphincter closes, resealing the junction between the esophagus and the stomach.

The ability of the lower esophageal sphincter to maintain a barrier between the stomach and the esophagus when swallowing is not taking place is aided by the fact that the last portion of the esophagus lies below the diaphragm, and is subject to the same abdominal pressures as is the stomach.

This prevents the formation of a pressure gradient between the stomach and esophagus that could force the stomach’s contents into the esophagus.

HeartburnSome people have less efficient lower esophageal sphincters, resulting in repeated episodes of refluxedgastric contents into the esophagus (gastro-esophagealreflux), heartburn, and in extreme cases, ulceration, scarring, obstruction, or perforation of the lower esophagus.

The lower esophageal sphincter not only undergoes brief periods of relaxation during a swallow but also in the absence of a swallow.

During these periods of relaxation, small amounts of the acid contents from the stomach are normally refluxed into the esophagus.

Multiple mechanisms, including neural and hormonal, regulate gastroesophageal sphincter pressure.

The musculature of the gastroesophageal sphincter has a tonic pressure.

It is normally higher than the intragastric pressure (the pressure within the stomach).

This high tonic pressure at the gastroesophageal sphincter keeps the sphincter closed.

Keeping this sphincter closed is important.

It prevents gastroesophageal reflux: the movement of substances from the stomach back into the esophagus.

The StomachThe Stomach

The stomach is a typically J shaped enlargement of the GI tract.

It connects the oesophagus to the duodenum (the first part of the small intestine).

Anatomy of the StomachAnatomy of the StomachThe stomach has four

(4) main regions:The cardiaThe fundusThe bodyThe pyloric region

The pyloric antrumThe pyloric canal The

phyloricsphinter

Histology of the StomachHistology of the StomachThe stomach wall is composed of the same four(4)

basic layers as the rest of the GI tract, with certain modifications.

The surface of the mucosa is a layer of simple columnar epithelial cells called mucous surface cells.

The epithelial cells extend down into the lamina propia, where they form columns of secretory cells called gastric glands that line many narrow channels called gastric pits.

Secretions from the gastric glands flow into each gastric pit and into the lumen of the stomach.

Gastric pits contain four (4) major secretory cells:Chief cells

Pepsinogen Activation of pepsinogen by low pH to form pepsin Once pepsin is formed, it can act on pepsinogen to produce more

pepsin Pepsin is a protease for protein digestion

Parietal cells HCl

Kills microbes in food Denatures protains Converts pepsinogen to pepsin

Intrincis factors Needed for absorption of vitamin B12

G-cells (enteroendocrine cell) Secretes gastrin hormone

Gastrin activates gastric juice secretion and gastric smooth muscle “churning”

Gastrin activates gastroileal reflex which moves chyme from ileum to colon

Mucus cells Protective role of mucus against acid and digestive enzymes

The submucosa layer of the stomach is composed of areolar connective tissue.

The muscularis has three (3) (rather than two) layers of smooth muscle:An outer longitudinal layerA middle circular layerAn inner oblique layer (limited to the body of

the stomach).

The serosa (simple squamous mesothelium and areolar connective tissue) covering the stomach is part of the viseral peritoneum.

Functions of the StomachFunctions of the StomachStorage

Because of its accordionlike folds (called rugae), the wall of the stomach can expand to store two to four liters of material. Temporary storage is important because you eat considerably faster than you can digest food and absorb its nutrients.

Mixing The stomach mixes the food with water and gastric

juice to produce a creamy medium called chyme.

Controlled release Movement of chyme into the small intestine is

regulated by a sphincter at the end of the stomach, the pyloric sphincter.

Physical breakdown Three layers of smooth muscles (rather than the usual

two) in the muscularis externa churn the contents of the stomach, physically breaking food down into smaller particles. In addition, HCl denatures (or unfolds) proteins and loosens the cementing substances between cells (of the food). The HCl also kills most bacteria that may accompany the food.

Chemical breakdown Proteins are chemically broken down by the enzyme

pepsin. Chief cells, as well as other stomach cells, are protected from self-digestion because chief cells produce and secrete an inactive form of pepsin, pepsinogen. Pepsinogen is converted to pepsin by the HCl produced by the parietal cells. Only after pepsinogen is secreted into the stomach cavity can protein digestion begin. Once protein digestion begins, the stomach is protected by the layer of mucus secreted by the mucous cells.

Hydrochloric Acid Production

HCl is produced in the parietal cells through a complex series of reactions.

Carbon dioxide diffuses into the parietal cell and the enzyme carbonic anhydrase catalyzes a reaction between the carbon dioxde and water to form carbonic acid.

Carbonic acid dissociates into bicarbonate ion and hydrogen ion and the bicarbonate ion is transported back into the bloodstream.

An ion exchange molecule in the plasma membrane exchange bicarbonate going out for chloride coming in.

Proton pumps powered by H+/K+ ATPases is used to transport the potassium and hydrogen ions.

The hydrogen ions are actively transported into the duct of the gastric gland and the negatively charged chloride ions diffuse with the positively charged hydrogen ions.

Potassium ions are counter transported into the parietal cells in exchange for hydrogen ions. The potassiun ions leak back into the lumen via potassium channels.

The net result is production of HCl in the parietal cells and its secretion into the duct of the gastric gland.

Four (4) chemical messengers regulate acid secretion: GastrinGastrin

released from G-cell stimulates acid secretion

Acetylcholine (Ach)Acetylcholine (Ach) released from the plexus neurons stimulates acid secretion

HistamineHistamine released from ECL cells stimulates acid secretion potentiates the response to gastrin and Ach.

Somatostatin Somatostatin – released from endocrine cells in the gastric wall Acts on parietal cells to inhibit acid secretion Inhibits release of gastrin and histamine

Parietal cell membranes contain receptors for all 4 of these molecules. Not only do these chemical messengers act directly on the parietal cells, they also influence each other’s secretion.

Pepsinogen secretion parallels acid secretion, i.e. most of the factors stimulate or inhibit acid secretion exert the same effect on pepsinogen secretion.

Three Phases of Gastric SecretionThree Phases of Gastric Secretion

Regulation of stomach secretion is divided into three (3) phases: • Cephalic• Gastric• Intestinal

Cephalic phase:Cephalic phase:

Taste, sight, tactile sensation of or thought of food in the mouth sends nervous impulse to the medulla oblongata.

These impulses cause parasympathetic neurons via the vagus nerves to stimulate secretion of HCl, pepsinogen and mucus in the stomach.

The parasympathetic stimulation also results in secretion of gastrin from the lower part of the stomach.

Gastrin travels through the bloodstream and further stimulated HCl and pepsinogen secretion in the upper and middle part of the stomach.

Gastric Phase:Gastric Phase:

Food has entered and distended the stomach. The pH of the stomach is also altered because protein has entered the stomach and buffered some of the stomach acid causing a low pH.

This distention activated a parasympathetic reflex via the medulla oblongate, and also has a direct stimulatory effect on the gastric glands. The result is the continued secretion of HCl and pepsinogen.

Negative feedback control of acid secretion is done by somatostatin. As the contents of the gastric lumen become more acidic, the stimuli that promote acid secretion decrease.

Intestinal phaseIntestinal phase Chyme has entered the duodenum

so gastric secretion is no longer needed.

When the chyme contains lipids from the digestion of fats or contains enough HCl to bring its pH to below 2, gastric secretion is inhibited.

The lipid and hydrogen ions inhibit gastric secretion by three simultaneous actions.

They cause impulses to go to the medulla oblongata to decrease parasympathetic stimulation of gastric glands

They set up local reflexes, via neurons in the wall of the gut, that decrease gastric secretion.

They cause the release of three local hormones collectively called enterogastrones (secretin, CCK inhibitory peptides) which travel via the circulation to the gastric glands and inhibit their secretion.

Gastric MotilityGastric Motility

After food enters the stomach, gentle, rippling, peristaltic movements called mixing waves pass over the stomach every 15-25 seconds.

These waves macerate food, mix it with gastric juice and reduce it to a soupy liquid called chyme.

As digestion proceeds, more vigorous mixing waves begin at the body of the stomach and intensify as they reach the pylorus.

As food reaches the pylorus, each mixing wave forces several milliliters of chyme into the duodenum through the pyloric sphincter.

Most chyme is forced back into the body of the stomach where mixing continues.

The next wave pushes the chyme forward again and forces a little more into the duodenum.

These forward and backward movement of gastric contents are responsible for most mixing in the stomach.

The rhythm of gastric waves are generated by pacemaker cells in the longitudinal smooth muscle layer.

These smooth muscle cells undergo spontaneous depolarization-repolarization cycles (slow waves) known as basic electrical rhythm of the stomach.

These slow waves are conducted through gap junctions along the stomach’s longitudinal muscle layer and also induce similar slow waves in overlying circular muscle layer.

Slow wave oscillations in the membrane potential of gastric smooth muscle fibers trigger bursts of action potentials when threshold potential is reached at the wave peak.

Membrane depolariztion bring the slow wave closer to threshold. Increasing the action potential frequency and thus the force of smooth muscle contraction.

Regulation of Gastric EmptyingRegulation of Gastric EmptyingStimulation of gastric emptying:

Gastric emptying, the periodic release of chyme from the stomach into the duodenum, is regulated by both neural and hormonal reflexes, as follows:

1. Stimuli (distention of the stomach, presence of partially digested proteins, alcohol and caffeine) initiate gastric emptying.

2. These stimuli increase the secretion of gastrin and generate parasympathetic impulses in the vagus (X) nerves.

3. Gastrin and nerve impulses stimulate contraction of the lower oesophagus sphincter, increase motility of the stomach and relax the pyloric sphincter.

4. The net effect of these actions is gastric emptying.

Inhibition of Gastric emptyingInhibition of Gastric emptying is controlled by the

enterogastric reflex and CCK.1. Stimuli (distention of the duodenum and the presence of

fatty acids, partially digested proteins and glucose) in the duodenal chyme initiate gastric emptying.

2. These stimuli the enterogastric reflex: Nerve impulses propagate from the duodenum to the medulla oblongata, where they inhibit parasympathetic stimulation and stimulate sympathetic activity in the stomach. The same stimuli also increase secretion of CCK.

3. Increased sympathetic impulses and CCK both decrease gastric motility.

4. The net effect if these actions is inhibition of gastric emptying.

PANCREATIC SECRETIONS

The proteolytic enzymes are secreted in inactive forms (zymogens) and then activated in the duodenum by other enzymes.

Activation is acquired in steps and is catalyzed by enterokinase. This is embedded in the luminal plasma membrane of the intestinal epithelial cells.

Proteolytic enzymes splits off a peptide from pancreatic trypsinogen thus forming the active enzyme trypsin

When activated trypsin which is also a proteolytic enzyem similarly splits off peptide fragments and in so doing activates the other pancreatic zymogens (this is in addition to its role in protein digestion).

Note bicarbonates function is to neutralize acid entering the deodenum from the stomach.

Also CCK responsible for the secretion of enzymes,(inclusive of those for fat, and protein digestion). CCK’s release is dependent on the levels/presence of fatty acids and amino acids in the duodenum

Glucagon, Insulin and Blood Glucose Regulation

The islets of Langerhans (clusters of emdocrine cells) secrets these two peptide hormones.

Insulin Secreted by beta cells of islets of Langerhans

within the pancreas when blood glucose level.Stimulates the uptake of glucose from the

blood stream and does this by increasing the transport of glucose from the blood to muscle cells and adipocytes. Also a net uptake of glucose by the liver.

Insulin secretion and subsequently signaling leads to the movement of a glucose transport protein GLUT 4 from the intracellular vesicles to the cell membrane. (*)

Once in the cell membrane the GLUT4 protein allows more glucose to enter the cell thus lowering the blood glucose level.

Note insulin secretion is not only dependent on blood glucose levels. Secretion is also dependent on:Elevated amino acid concentration Hormonal controls The autonomic neurons to the islets of

Langerhans

Glucagon Secreted by the alpha cells of Langerhans

within the pancreas at low blood glucose levels also by neural and hormonal inputs to these islets.

Stimulates the release of glucose to the blood stream.

It binds to specific receptors to set off a chain of events which makes glucose available i.e. Increased glycogenolysis (glycogen break

downIncreased gluconeogenesisIncreases in the synthesis of ketones

BILE SECRETION AND LIVER FUCTION

Bile is secreted by liver cells into a number of small ducts (the bile canaliculi which converge to form the common hepatic duct.

Note bile salts and lecithin are synthesized in the liver and helps to solubilize fat in the small intestine

Where as cholesterol, bile pigments and trace metals are extracted from the blood by the liver and excreted via the bile.

Bicarbonate ions neutralize acid in the duodenum

When fatty meals are being digested most of the bile salts entering the intestinal tract via bile are absorbed by specific sodium-coupled transporters in the ileum.

Absorbed bile salts are returned via the portal vein to the liver where they are secreted once again.

Bile salts uptake from portal blood into hepatocytes is driven by secondary active transport coupled to sodium

Cholesterol homeostasis in the blood and the process by which cholesterol –lowering drugs work is maintained by the secretion of bile followed by the excretion of cholesterol in feces.

Bile pigments are substances formed from the heme portion of hemoglobin when digestion of old or damaged erythrocytes occurs in the spleen and liver.

Bile components are secreted by two different cells, they are:Hepatocytes which secrets bile salts and pigments, lecithin.Epithelial cells which secrets most of the bicarbonate rich salt

solutions

Secretion of the salt solution by the bile ducts is stimulated by secretin in response in response to acidity in the duodenum.

Note the secretion of bile salts is controlled by the concentration of bile salts within the blood

The liver is always secreting bile however, greater secretion occurs at meal times (during and just after).

The sphincter of oddi is a ring of smooth muscles surrounding the common bile duct at the point at which it enters the duodenum. When closed the diluted bile secreted by the liver is shunted into the gallbladder. It is at this point the organic components of bile (water and sodium chloride) are absorbed into the blood

The Small Intestine

SecretionIntestinal epithelium secretes mineral ions such

as, sodium, chloride and bicarbonate ions into the lumen and water follows by osmosis.

Chloride is the primary ion that determines the magnitude of fluid secretion.

Various hormonal ,paracine signals as well as toxins and bacterial toxins can increase the frequency of these channels and fluid secretion.

Water movement into the lumen occurs when the stomach is hypertonic, this then causes osmotic movement of water.

AbsorptionAll fluid secreted by the small intestine is

absorbed back into the blood.Large volumes of fluid which includes, salivary,

gastric, hepatic, pancreatic secretions and ingested water is simultaneously absorbed from lumen into the blood.

There is a large net absorption of water from small intestine.

Absorption is achieved by transport of ions mostly sodium from lumen into the blood with water followed by osmosis.

MotilityStationary concentration and relaxation of

intestinal segments occurs during the digestion of a meal.

Each contracting segment is a few cm long and the digestion last for a few seconds.

Chyme in the lumen is forced up and down the intestine.

Segmentation- the rhythmical contraction and relaxation of the intestine.

Mixes the chyme in lumen and bringing it into contact with intestinal wall.

Segmentation movement-initiated by electrical activity by pacemaker cells with circular smooth muscle layer.-intestinal basic electrical rhythm produces oscillations in the smooth muscle membrane potential. If threshold is reached action potentials are triggered that increase muscle contraction.-the frequency of segmentation is set by the frequency of the intestinal basic rhythm-unlike the stomach that has a single rhythm 3 mins/sec intestinal rhythm varies along the length of the intestine.-each successive region have a slightly lower frequency than the above

MotilityProduces a slow migration of the intestinal

contents toward the large intestine.

Segmentation intensity can be altered by hormones:

Enteric nervous system and autonomic nerves.

Parasympathetic activity increases the force of contraction.

Sympathetic stimulation decreases it.

Migrating myoelectric complexBegins in the lower portion of stomach.

Repeated waves of peristaltic activity.

Moves any undigested material remaining in the small intestine into the large intestine that is long enough to grow and multiply excessively.

Rise in plasma concentration of intestinal hormone MOTILIN initiates MMC.

Motilin stimulates MMCs via both the enteric and autonomic nervous system.

MotilityContractile activity in certain regions of the

small intestine can be altered by reflexes.

Eg, segmentation intensity in the ileum increases during periods of gastric emptiness (gastroileal reflex)

Intestino intestinal reflex lead to complte cessastion of motility.

Large Intestine6.5CM in diameter, 1.5m longFirst portion CecumCecum forms a blind ended pounch that

extends to appendixCOLON: 3 SEGMENTSAscendingTransverseDescending (forms sigmoid colon)Function –is to store and concentrate faecal

material before defecation.

Large intestineChyme enters the cecum through the ilocecal

sphincter.Sphincter relaxes each time the terminal

portion of the ileum contracts.Chyme enters the large intestine.The primary absorptive process in the intestine

is active transport of Na+ from lumen to blood. Also osmotic absorption of water.

There is a net movement of K+ from blood into the large intestine lumen. Stimulated by cAMP

Motility &DefecationContraction of circular smooth muscle produce

segmentation motion.Slower than small intestineFollowing a meal a wave contraction known as

mass movement spreads over transverse segment of intestine to rectum

Unlike a peristaltic wave in the small intestine, the smooth muscle in the intestine remains contracted for some time after mass mov’t

Parasympathetic input increases segmental contractions whereas sympathetic input decreases colonic contractions

PATHOPHYSIOLOGY OF THE GASTROINTESTINAL TRACT

Peptic Ulcer Disease, Vomiting and Gallstones, Lactose Intolerance, IBD, Constipation and Diarrhoea

DEFINITION

Peptic Ulcer Disease (PUD)= These are areas of tissue degradation that can be caused by increased acid and pepsin or impaired mucosal defenses such as decreased bicarbonate secretions.

Ulcers are normally found in the stomach (gastric), duodenum (duodenal) and oesophagus (oesophagal).

Common Risk Factors for Gastric Mucosal Disruption

Associated with Helicobacter pylori.AlcoholNSAID- Induced gastritis or ulcers are

frequently “silent”.CorticosteroidsTobaccoCoffee/ Caffeine

Clinical Manifestation

Pain (epigastic burning)

Nausea, vomiting or bloating

Weight Loss

Upper Gastrointestinal haemorrhaging or blood in the stomach

Diagnostic MethodsAbdominal X-ray

Blood Count

Endoscopy and biopsy of ulcer

H pylori testing

TherapyIn mild disease, treat with bismuth or

misoprostal

For H pylori give antibiotics

Vomiting

Vomiting is the forceful expulsion of the contents of the stomach and upper intestinal tract through the mouth.

It is a complex co-ordination by a region in the brainstem, the medulla oblongata.

Causes of VomitingGastric contents get into the respiratory tract

Food poisoning

Overeating

Concussion

Vomiting can be induced by stimulation of the chemoreceptor zone, vestibular apparatus and the GI tract

ConsequencesIntestinal Blockage

Aspiration Pneumonia

Disturbances in acid-base balance

Dehydration

Electrolyte Depletion

Diagnosis

Blood Tests- to check electrolytes and blood cell count

Urinalysis- to check for dehydration and infection

CT Scan- to check for head injuries

X-ray

Treatment

Most of the time, vomiting go away on their own and could be managed at home.

If vomiting occurs, fluids are given by the mouth or through a vein into the bloodstream.

GallstonesGallstones are solid particles that form from

the bile in the gallbladder. There are two types of them: 1. Cholesterol Stones and 2. Pigment Stones.

Gallstones can be any size, from as tiny as a grain of sand to large as a golf ball.

Problems of Gallstones

Gallstones within the gallbladder often cause no problems. If they are too large or too many, they cause extreme pain. They may also cause problems if they move out of the gallbladder.

If there movements lead to blockage of any of the ducts connecting the gallbladder, liver or pancreas with the intestine, serious complications may occur.

Blockage of a duct can cause bile or digestive enzymes to be trapped in the duct.

If these conditions go untreated, they can even cause death.

Gallstone Causes

The stones form when the amount of cholesterol or bilirubin in the bile is high.

Pigment stones form most often in people with liver disease or blood disease, who have high levels of bilirubin.

Poor muscle tone may keep the gallbladder from emptying completely. The presence of residual bile may promote the formation of gall stones.

Risk Factors for the Formation of Gallstones

Female Gender

Being Overweight

Losing a lot of weight quickly on a starvation diet

Taking of certain medications such as birth control pills or cholesterol lowering drugs.

TreatmentIntake of only clear liquids to give the

gallbladder a rest.

Avoid fatty or greasy meals.

Use of painkillers.

Use of drugs made with bile acids.

Gallstone surgery called Cholecystectomy.

LACTOSE INTOLERANCE

LACTOSE-milk carbohydrate-digested by LACTASE, into its components

absorbed by glucose & galactose

active transport

LactaseEnzymeEmbedded in luminal plasma membranes of

intestinal epithelial cellsPresent at birthProduction decreases after 2 yrs

Lactose intolerance- inability to digest lactase.

Increases concentration in small intestineDecreases osmotic gradient, therefore, water

retained in lumen.Lactose-containing fluid moves to large

intestine

bacteria digests lactose metabolizes

monosaccharides

produces gas & short chain fatty acids

Gas distends colon and produces painShort chain fatty acids draws water into

intestinal lumen which leads to diarrheaLactose intolerance causes mild discomfort to

severe dehydrating diarrhea

Solution: lactose free products/lactase tablets

INFLAMMATORY BOWEL DESEASE (IBD)

Crohn’s Disease & Ulcerative Colitis

Chronic inflammation of the bowel

Crohn’s DiseaseOccurs anywhere along GI tract (mouth–

anus)Most common at the end of the ileumInflammation and thickening of bowel wall

causes narrowing or blockage of lumen and hence, pain

1st symptoms – pain in lower right abdomen & diarrhea (sometimes fever)

Often mistaken for acute appendicitis

Relief: defecation (temporary)

ColitisConfined to colon

Caused by disruption of normal mucosa with bleeding, edema & ulcerations

In an extreme case bowel wall thins and tissue lost, so holes break bowel wall

Symptoms: diarrhoea , rectal bleeding, abdominal cramps

IBD con’t

Most common in caucasians (late teens to early 20’s and > 60)

Caused by environmental and genetic factors

As a result of weak immune system and poor tissue repair

Responses to normal microorganisms in intestinal lumen

TreatmentInitially – 5-aminosalicylate drugs

e.g. sulfasalazine antibacterial & anti-inflammatory

effectIn severe case – glucocorticoids or removal of

diseased bowelNew drug therapy – immunosuppressive medicinesDiet changes aid in healing

(NB: overuse of glucocorticoids may cause bone loss)

CONSTIPATION AND DIARRHEA

Common Belief: Unless you have a bowel movement everyday, ‘toxic’ substances from fecal matter (in large colon) will poison you!

WHAT DO YOU THINK???

Toxic agents after a prolonged period of time – still to be discovered

HOWEVER, fecal retention for days or weeks may lead to:-

Headache Loss of appitite Nausea Abdominal distention

These are all symptoms of

CONSTIPATION

The longer the fecal matter remains in large intestine, the more water absorbed, feces become drier and defecation becomes difficult and painful

Common in the elderly, or anyone with damage to the enteric nervous system (decreased motility of large intestine) or emotional stress

Cure –distension from dietary fibre or laxatives

Dietary fibre – cellulose & other complex polysaccharides

- not digested in small intestine, produces distension in large intestine, leads to motility

- Bran, Fruits, Veggies

Laxatives – increase frequency/ease of defecation - fiber is a laxative - mineral oils (lubricate feces) - Mg & Al salts (epsom salts) (water

retention) - Caster oil (stimulates intestinal tract) - causes dependence

DiarrheaLarge, frequent, watery, stools

Causes: fluid absorption, fluid secretion

Increased motility caused by distension (not the other way around!)

Secretory diarrhoea – bacterial, protozoan & viral diseases (E. coli)

- Cholera and Traveller's diarrhoea

CHOLERA

- Caused by bacteriaReleases toxin that stimulates cyclic AMP

Opens chloride channels

Increase in chloride ions

Increase water content in lumen

Massive life threatening diarrhoea (dehydration, decreased blood vol.)

TRAVELLER’S DIARRHEA- Produced by several species of bacteria,

parasites, viruses- Produces secretary diarrhoea (same process

at cholera)

Other consequences of severe diarrhoea are potassium depletion, metabolic acidosis

TreatmentDehydrating effect can

be balanced by drinking salt-glucose solution to replace fluids (by active transport).

Until diarrhoea subsides, a change is diet can help. Avoid caffeine, greasy foods, high fibre foods and lactose rich foods