Digestive System.
The digestive system is responsible for the intake, processing,
and absorption of ingested nutrients and water.
It is critical to the provision of substrates, minerals, vitamins, and water,
and to the regulation of metabolic processes through out the body.
Normal function is necessary for whole body homeostasis,
as well as normal functioning of individual organ systems.
First, the endocrine, neural, and paracrine control of gastrointestinal function,
illustrates the general principle of physiology that information flow between cells, tissues,
and organs is an essential feature of homeostasis,
and allows for integration of physiological processes.
This is highlighted by the intimate relationship,
between the absorptive capacity of the gastrointestinal tract,
and the circulatory and lymphatic system as pathways to deliver these nutrients to the tissues.
Second, many of the functions of the gastrointestinal tract illustrates,
the general principle of physiology that most physiological functions,
are controlled by multiple regulatory systems, often working in a position.
For example, the acidity of the contents of the stomach is increased or decreased,
by the influence of hormones released from the gastrointestinal tract,
as well as paracrine factors, and neural inputs.
Third, the epithelium of the digestive tract regulates the transfer of materials,
from the environment to the blood, which exemplifies the general principle of physiology,
that control exchange of materials occurs between the compartments,
and across the cellular membranes.
Fourth, the very process of digestion depends on basic chemistry,
reflecting yet another principle of physiology,
that physiological processes are dictated by the laws of chemistry and physics.
Finally, there are many examples of how form and function,
are related at all levels of structure from cells to organs of the digestive system,
which illustrates the general principle of physiology that structure is a determinant of -
and has coevolved with - function.
One of the most vivid examples is the large surface area for absorption of ingested materials,
made possible by morphological specialisations of the small intestine.
Overview of the digestive system.
The digestive system includes the gastrointestinal tract, or alimentary canal,
- consisting of the mouth, pharynx, esophagus, stomach, small intestine, large intestine,
and anus - and the accessory organs and tissues - consisting of the salivary glands,
liver, gallbladder, and exocrine pancreas.
The accessory organs are not part of the tract,
but secrete substances into it via connecting ducts.
The overall function of the digestive system is to process ingested foods into molecular forms,
that are then transferred, along with small molecules, ions, and water,
to the body’s internal environment, where the circulatory system can distribute them to cells.
The adult gastrointestinal tract is a tube approximately 9 meters in length,
running through the body from mouth to anus.
This is the approximate length in human cadavers: in life,
the tract is shorter due to tonic contractions of the smooth muscle in its walls.
The lumen of the tract is continuous with the external environment,
which means that its contents are technically outside the body.
This fact is relevant to understanding some of the tracts properties.
For example, the large intestine is colonised by billions of bacteria,
most of which are harmless and even beneficial in this location.
However, if the same bacteria enter the internal environment, as may happen, for example,
if a portion of the large intestine is perforated, they may cause a severe infection.
Most food enters the gastrointestinal tract as large particles containing macromolecules,
which are unable to cross the intestinal epithelium.
Before ingested food can be absorbed,
it must be dissolved and broken down into smaller molecules.
Small nutrients such as vitamins and minerals do not need to be broken down,
and can cross the epithelium intact.
The dissolving and breaking down process is called digestion,
and is accomplished by the action of a variety of digestive enzymes,
and other chemicals released by the system’s and other chemicals,
released by the endocrine glands.
Polysaccharide digestion is initiated by the enzyme amylase,
triglyceride digestion by the enzyme lipase, and proteins are digested by a variety of proteases.
These enzymes are released into the lumen of the GI tract through the process of secretion,
in which the enzymes are released from exocrine cells,
by exocytosis into a duct that connects to the GI tract.
In addition, the digestive enzymes are located on the apical membranes,
of the intestinal epithelium.
Carbohydrates are broken down into monosaccharides, glucose, fructose, and galactos.
Proteins are broken down into 20 different amino acids.
Triglycerides are broken down to monoglyceride plus 2 free fatty acids.
The molecules produced by digestion, along with water and small nutrients,
that do not require digestion, then move from the lumen of the gastrointestinal tract,
across a layer of epithelial cells and enter the interstitial fluid.
This process is called absorption.
Absorbed fats and fat soluble nutrients are taken up by the lymphatic vessels,
that ultimately empty into large veins near the heart.
All other absorbed nutrients enter directly into capillaries that drain into veins,
and eventually merge to form the hepatic portal vein.
The hepatic portal vein drains into the liver.
While secretion, digestion, and absorption are taking place,
contractions of smooth muscles in the gastrointestinal tract wall occur,
where they serve two functions:
They mix the luminal contents with the various secretions,
and they move the content through the tract from mouth to anus.
These contractions are referred to as the motility of the gastrointestinal tract.
In some cases, muscular movements travel in a wave like fashion in one direction along the
length of a path of the tract, a process called peristalsis.
The functions of the digestive system can be described in terms of 4 major processes,
- secretion, digestion, absorption, and motility - and the mechanisms controlling them.
Digestion begins with chewing in the mouth,
where large pieces of food are broken up into smaller particles,
mixed with secretions of the salivary glands, and formed into a rounded mass called bolus.
The next segments of the tract, the pharynx and oesophagus,
do not contribute significantly to digestion, but the muscles in the walls of the segments,
participate in the swallowing reflex that moves ingested food and drink to the stomach.
The stomach is a saclike organ that functions to store, dissolve,
and partially digest the macromolecules in food,
and to regulate the rate at which it empties its contents into the small intestine.
Secretion of hydrochloric acid by cells in the wall of the stomach,
creates a highly acidic gastric environment.
The mixture of ingested food particles and gastric secretions is referred to as chyme.
The majority of the digestive process occurs in the next section of the tract, the small intestine.
It is by far the longest section, and is divided into three regions.
The duodenum section and the ileum is the terminal region,
from which the chyme enters the large intestine.
The surface area of the small intestine is vastly increased by finger like projections called villi.
Aided by secretions that flow via ducts from the liver and pancreas,
the small intestine digest all the categories of macromolecules into molecules,
small enough to be transported through the epithelial lining of the tract wall.
The final section of the tract, the large intestine,
concentrates undigested material by absorbing most of the remaining ions and water.
It also serves to temporarily store the undigested material,
until it is expelled by the body in the feces.
The large intestine contains billions of beneficial bacteria,
(collectively known as the microbiome),
that metabolise some of the substances not absorbed by the small intestine.
Some products of bacterial metabolism are absorbed into the blood,
and provide important health benefits to other body systems.
With a few exceptions, the digestive system will absorb,
all of a particular nutrient that is ingested.
Therefore, the digestive system is not generally responsible ,
for the homeostatic control of nutrient concentrations in the internal environment.
Instead, the plasma concentration and distribution of the absorbed,
nutrients throughout the body are primarily controlled by hormones,
from a number of endocrine glands and by the kidneys.
Small amounts of certain metabolic end products are excreted via the gastrointestinal tract,
primarily by way of the liver.
This represents a relatively minor function of the GI tract in healthy individuals - elimination.
In fact, the lungs and kidneys are usually responsible,
for eliminating most of the body’s waste products, such as CO2 and urea.
The feces leave the system via the anus at the end of the gastrointestinal tract.
Feces consists all most entirely of bacteria and ingested material,
that was neither digested nor absorbed,
and therefore was never actually within the internal environment.
The GI tract also has a variety of immune functions, allowing it to produce antibodies,
and fight ingested microorganisms that are not destroyed by the acidity of the stomach.
For example, the small intestine has regions of lymphatic nodules that contain immune cells;
these cells secrete factors that alter intestinal motility and kill microorganisms.
The average American adult consumes about 500 to 800 grams of food,
and 1200 millilitres of water per day, but this is only a fraction of the materials,
entering the lumen of the gastrointestinal tract.
An additional 7000 millilitres of fluid from salivary glands, gastric glands, pancreas, liver,
and intestinal glands are secreted into the tract each day.
Salivary glands secrete 1500 millilitres.
Gastric secretions contributes 2000 millilitres.
Bile from the gallbladder contributes 500 millilitres.
Pancreatic secretions contribute 1500 millilitres.
Of the approximately 8 litres of fluid entering the tract each day, as much as 99% is absorbed.
6700 millilitres are absorbed into blood in the small intestine.
1400 millilitres is absorbed into blood in the large intestine.
The small amount of fluid loss represents only 4% of the total fluids,
lost from the body each day.
Most fluid loss is via the kidneys and respiratory system.
Almost all the ions in the fluids that are secreted into the GI tract,
are also reabsorbed into the blood.
Moreover, the secreted digestive enzymes are themselves digested,
and the resulting amino acids are absorbed into the blood.
Structure of the gastrointestinal tract wall.
From the mid oesophagus to the anus, the wall of the GI tract has a similar structure.
In some regions, the apical (luminal) surface is highly convoluted,
a feature that greatly increases the surface area available for absorption.
From the stomach on, the surface is covered by a single layer of epithelial cells,
linked together along the edges of their apical surfaces by tight junctions.
Invagination of the epithelial into the underlying tissue form exocrine glands that secret acid,
HCO3- , digestive enzymes, water, ions, and mucus into the lumen.
Other cells into the epithelium secrete hormones into the blood,
that are important in regulating various aspects of digestion and appetite.
Surrounding the epithelium is the lamina propria, which is the layer of loose connecting tissue,
through which pass small blood vessels, neurons and lymphatic vessels.
The lamina propria is separated from underlying tissues by the muscularis mucosa,
which is a thin layer of a smooth muscle involved int small movements of the mucosal surface.
The combination of these 3 layers - the epithelium, lamina propria, and the muscularis mucosa -
is called the mucosa.
This is the region where much of the processes of digestion and absorption takes place.
Outside of the mucosa is the submucosa, which is a second connective tissue layer.
This layer also contains blood and lymphatic vessels, and a network of neurons,
the submucosal plexus.
Neurons project from this network to the mucosa.
Surrounding the submucosa are layers of smooth muscle called muscular externa.
Contractions of these muscles provide the forces,
for moving and mixing the gastrointestinal contents.
Except in the stomach, which has three layers, elsewhere the musclaris externa has two layers.
A relatively thick inner layer of muscle, the fibres of which are oriented in a circular pattern,
around the tube, so that the contraction produces a narrowing of the lumen.
A thinner outer layer of longitudinal muscle, the contraction of which shortens the tube.
Between these two muscle layers is a second network of neurons,
known as the myenteric plexus.
Neurons interconnect these network with the submucosal plexus.
The myenteric plexus is innervated by nerves,
from the sympathetic and parasympathetic divisions of the autonomic nervous system.
Finally, the outer surface of the tube is a thin layer of connecting tissue called the serosa.
Thin sheets of connective tissue connect the serosa to the abdominal wall,
and support the GI tract in the abdominal cavity.
Epithelial surfaces in the GI tract are continuously being replaced by new epithelial cells.
In the small intestine, for example, new cells arise by cell division from cells,
at the base of the finger like villi that project into the lumen.
These cells differentiate as they migrate to the top of the villi, replacing older cells that die,
and are discharged into the intestinal lumen.
These dead cells release their intracellular enzymes into the lumen,
which then contribute to the digestive process.
About 17 billion epithelial cells are replaced each day,
and the entire epithelium of the small intestine is replaced in about 5 days.
It is because of this rapid cell turnover,
that the lining of the intestinal tract is so susceptible to damage by treatments,
that inhibit cell division, such as anti cancer drugs and radiation therapy.
Also, at the base of the villi are enteroendocrine cells that secrete hormones,
that control a wide variety of gastrointestinal functions,
including motility and exocrine and pancreatic secretions.
Regulation of gastrointestinal processes.
Unlike control systems that regulate variables in the internal environment,
the control mechanisms of the digestive systems primarily regulate conditions in the lumen,
and wall of the GI tract.
With few exceptions, these control mechanisms are governed by the volume and composition,
of the luminal contents rather than by the nutritional state of the body.
GI reflexes are initiated by a relatively small number of luminal stimuli :
- Distension of the wall by the volume of the luminal contents.
- Chyme osmolarity (total solute concentration).
- Chyme acidity.
- Chyme concentrations of specific digestion products like monosaccharides, fatty acids,
peptides and amino acids.
These stimuli act on mechanoreceptors, osmoreceptors,
and chemoreceptors located in the wall of the tract and trigger reflexes,
that influence the effectors - the muscle layers in the wall of the tract,
and the exocrine glands that secrete substances into its lumen.
Neural regulation.
The GI tract has its own local neural control, a division of the autonomic nervous system,
known as the enteric nervous system, composed of two nerve plexuses,
the myenteric and submucosal.
These neurons either synapse with other neurons within a given plexus,
or end near smooth muscles, glands, and epithelial cells.
Many axons leave the myenteric plexus and synapse with neurons in the submucosal plexus,
and vice versa, so that neural activity in one plexus influences the activity in the other.
Moreover, stimulation at one point in the plexus can lead to impulses,
that are conducted longitudinally up and down the tract.
For example, stimuli in the upper part of the small intestine may affect smooth muscle and gland activity,
in the stomach as well as in the lower part of the intestinal tract.
In general, the myenteric plexus influences smooth muscle activity and motility,
whereas the submucosal plexus influences gland function and secretory activity.
The enteric nervous system contains adrenergic and cholinergic neurons,
as well as neurons that release other neurotransmitters,
such as nitric oxide, several neuropeptides, and ATP.
Interactions between neurons of the enteric nervous system and the effectors mentioned previously -
muscles cells and exocrine glands - permit neural reflexes that occur entirely within the tract,
independent of the CNS.
In addition, efferent neurons from both the sympathetic and parasympathetic branches,
of the autonomic nervous system enter the intestinal tract and synapse with neurons with both plexuses.
Via these pathways, the CNS can influence the motility and secretory activity of the GI tract.
Thus, two types of neural-reflex arcs exists.
1. Short reflexes from receptors through the nerve plexuses to effector cells all within the GI tract.
2. Long reflexes from the receptors in the tract to the CNS by way of afferent nerves,
and back to the nerve plexuses and effector’s cells by way of autonomic nerves.
Finally, it should be noted that not all neural reflexes are initiated by signals in the tract.
Hunger, the sight or smell of food, and the emotional state of an individual,
can have significant effects on the GI tract, effects that are mediated by the CNS via autonomic neurons.
Hormonal regulation.
The hormones that control the GI system as secreted mainly by enteroendocrine cells,
scattered throughout the epithelium of the stomach and small intestine - that is,
these cells are not clustered into discrete endocrine glands, like the thyroid or adrenal glands.
One surface of each endocrine cell is exposed to the lumen of the GI tract.
At this surface, various chemical substances in the chyme stimulate the cells,
to secrete its hormones from the opposite side of the cell into the blood.
The gastrointestinal hormones reach their target cells via the circulation.
The four best understood GI hormones are :
- Secretin
- Cholecystokinin (CCK)
- Gastrin
- Glucose dependent insulinotropic peptide (GIP).
Two generalisations can be made of GI hormones.
1. Most of the hormones participate in a feedback control system that regulates,
some aspect of GI luminal environment.
2. Most GI hormones affect more than one type of target cell.
These two generalisations can be illustrated by CCK.
The presence of fatty acids and amino acids in the small intestine triggers CCK secretion,
from cells in the small intestine into the blood.
Circulating CCK then stimulates the pancreas to increase the secretion of digestive enzymes,
causes the gall bladder to contract, and relaxes the sphincter, that allows pancreatic and liver secretions,
to flow into the small intestine.
As fatty acids and amino acids are absorbed, their concentrations in the lumen decrease,
removing the signal for CCK release.
In many cases, a single effector cell contains receptors for more than one hormone,
as well as receptors for neurotransmitters and paracrine substances.
The results is a variety of inputs that can affect the cells response.
One such event is the phenomenon known as potentiation,
in which the response of an effector to a hormone is greatly increased,
when a second hormone is also present.
In this type of interaction, the magnitude of the effector response to the two hormones,
is greater than would be predicted by the sum of their individual stimulatory effects.
One of the consequences is that small changes in the plasma concentration,
of one gastrointestinal hormone can have large effects on the actions of other gastrointestinal hormones.
In addition to the stimulation (or, in some cases, inhibition) of effective cell functions,
the gastrointestinal hormones also have trophic (growth promoting) effects on varies tissues,
including the gastric and intestinal mucosa of the exocrine portions of the pancreas.
Finally, many additional GI hormones, some of which called incretins,
are involved in the control of blood glucose by serving as a feedforward signal,
from the GI tract to the endocrine pancreas:
Others may regulate appetite.
Properties of gastrointestinal hormones.
Gastrin.
Gastrin is a peptide.
It is produced in the antrum of the stomach.
The stimuli for hormone release is amino acids; peptides in stomach; parasympathetic nerves.
Factor inhibiting hormone release are acid in stomach; somatostatin.
It stimulates acid secretion in the stomach.
It stimulates motility in the stomach.
It stimulates ileum motility in the small intestine.
It stimulates mass movement in the large intestine.
CCK.
It is a peptide.
It is produced in the small intestine.
The stimuli for hormone release is amino acids, fatty acids in the small intestine.
It inhibits acid secretion in the stomach.
It inhibits motility in the stomach.
It potentiates secretin’s actions by HCO3- secretion in the pancreas.
It stimulates insulin secretion in the pancreas.
It potentiates secretin’s actions by HCO3- secretion in the bile ducts of the liver.
It stimulates gallbladder contractions.
It relaxes sphincter of Oddi.
Secretin.
It is a peptide.
It is produced in the small intestine.
The stimuli for hormone release is acid in the small intestine.
It inhibits acid secretion in the stomach.
It inhibits motility in the stomach.
It stimulates HCO3- secretion in the pancreas.
It potentiates CCK’s actions by enzyme secretion in the pancreas.
It stimulates HCO3- secretion in the bile ducts of the liver.
GIP.
It is a peptide.
It is produced in the small intestine.
The stimuli for hormone release is glucose, fat in the small intestine.
It stimulates insulin secretion.
Phases of gastrointestinal control.
The neural and hormonal control of the digestive system is, in large part, divisible into three phases.
- Cephalic.
- Gastric.
- Intestinal.
According to where the stimulus is perceived.
The cephalic phase is initiated when sensory receptors in the head are stimulated by sight,
smell, taste, and chewing.
Various emotional states can also initiate this phase.
The efferent pathways for these reflexes are primarily mediated by parasympathetic neurons,
carried in the vagus nerves.
They activate neurons in the gastrointestinal nerve plexus,
which in turn affect secretory and contractile activity.
Four stimuli in the stomach initiate the reflexes that constitute the gastric phase of regulation:
- distension.
- acidity.
- amino acids.
- peptides.
Formed during the partial digestion of ingested protein.
The responses to these stimuli are mediated by short and long neural reflexes,
and by the release of the hormone gastrin.
Finally, the intestinal phase is initiated by stimuli in the small intestine including distension, acidity,
osmolarity, and various digestive products.
The intestinal phase is mediated by both short and long neural reflexes, and by the hormones secretin,
CCK, and GIP, which has secreted by enteroendocrine cells of the small intestine.
We must emphasise that each of these phases is named for the site,
at which the various stimuli initiate the reflex, and not for the sites of effector activity.
Each phase is characterised by efferent output to virtually all organs in the gastrointestinal tract.
Also, these phases do not occur in temporal sequence except at the very beginning of a meal.
Rather, during ingestion and the much longer absorptive period,
reflexes characteristics of all three phases may be occurring simultaneously.
Mouth, pharynx and oesophagus.
In these initial portions of the gastrointestinal tract, whole bytes of food are chopped into smaller bits,
mixed with salivary secretions, moulded into a slippery bolus, and swallowed.
While little digestion or absorption actually takes place, the stimulation of sensory and mechanoreceptors, triggers the cephalic phase signals that activate subsequent regions of the tract.
This is an excellent example of a feed forward control system.
Saliva.
Saliva is secreted through a series of short ducts from three pairs of salivary glands,
- Parotid gland,
- Sublingual gland,
- and Submandibular gland.
It contains mucus, water, HCO3- , and several enzymes.
Saliva moistens and lubricates food particles for swallowing, and buffers the acidity of ingested foods,
and of metabolites from bacteria living on or around the teeth.
Mucus is a viscous, slippery, glycoprotein rich protective secretion produced by epithelial cells,
through out the gastrointestinal tract.
Protection from potentially harmful bacteria is provided by salivary lysozyme, and anti bacterial enzyme, found in tears and nasal secretions.
Saliva also contains amylase and lipase, which begins the digestion of polysaccharides and triglycerides.
These salivary enzymes play a minor role in digestion overall,
because of the limited time they have to act on food,
before they are inactivated by the acidic environment of the stomach.
Another function of saliva is to dissolve some of the food molecules.
Only in the dissolved state can these molecules react with chemoreceptors in the mouth,
giving rise to the sensation of taste, and the activation of cephalic phase reflexes.
Components and functions of saliva.
Water.
Moistens food and dissolves molecules to facilitate chemoreception.
Mucus.
Lubricates food and facilitates formation of a bolos for swallowing.
HCO3-.
Neutralises acids in food and bacterial metabolites.
Lysozyme.
Kills bacteria to maintain health of gums and teeth.
Amylase.
Begins the digestion of polysaccharides.
Lipase.
Begins the digestion of triglycerides.
The secretion of saliva is controlled by both sympathetic and parasympathetic neurons.
Unlike their antagonistic activity the most organs, both systems stimulate salivary secretion,
with the parasympathetic neurons producing the greater response.
There are no hormonal regulation of salivary secretion.
In the absence of ingested material, a low rate of salivary secretion keeps the mouth moist.
The smell or sight of food induces a cephalic phase of salivary secretion.
This reflex can be conditioned to other cues, a phenomenon made famous by Pavlov,
who conditioned dogs to salivate in response to a sound cue,
by repeatedly presenting the sound when food was offered.
Salivary secretion can increase markedly in response to a meal.
The reflex is initiated by chemoreceptors (acidic foods are particularly strong stimuli),
and pressure receptors in the walls of the mouth and on the tongue.
Increased saliva secretion is accomplished by a large increase in blood flow to the salivary glands,
which is mediated primarily by an increase in parasympathetic neural activity.
At its maximum, the volume of saliva secreted per gram of tissue,
is the largest secretion of any of the body’s exocrine glands.
Chewing.
Chewing is controlled by the somatic nerves to the skeletal muscles of the mouth and jaw.
Although chewing is a voluntary activity, it is coordinated by pattern generator circuits in the brain stem,
and reflexes activated by the pressure of food against the gums, hard palate at the roof of the mouth.
Activation of these mechanoreceptors leads to reflexive inhibition of the muscles holding the jaw closed.
The resulting relaxation of the jaw reduces the pressure on the various mechanoreceptors,
leading to a new cycle of contraction and relaxation.
Chewing prolongs the subjective pleasure of taste.
Chewing also breakups food particles, creating a bolus that is easier to swallow, and possibly, digest.
Attempting to swallow a large particle of food can lead to chocking if the particles lodges over the trachea,
blocking the entry of air into the lungs.
Swallowing.
Swallowing is a complex reflux 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 centre in the medulla oblongata of the brainstem.
This centre then elicits swallowing via efferent fibres to the muscles in the pharynx and oesophagus,
as well as to the respiratory muscles.
As the ingested materials moves into the pharynx,
the soft palate elevates and lodges against the back wall of the pharynx,
preventing food from entering the nasal cavity.
Impulses from the swallowing centre inhibit respiration, raise the larynx,
and close the glottis (the area around the vocal chords and the space between them),
keeping 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 the cover the glottis.
This prevents aspiration of food, a potentially dangerous situation in which food travels down the trachea, and can cause choking,
or when regurgitated stomach contents are allowed into the lungs causing damage.
The next stage of swallowing occurs in the oesophagus, the tube that passes through the thoracic cavity,
penetrates the diaphragm (which separates the thoracic cavity from the abdominal cavity),
and joins the stomach a few centimetres below the diaphragm.
Skeletal muscles surrounds the upper third of the oesophagus,
and smooth muscle surrounds the lower two thirds.
The pressure in the thoracic cavity can be negative relative to atmospheric pressure,
and this subatmospheric pressure is transmitted across the thin wall of the intrathoracic portion,
of the oesophagus to the lumen.
In contrast, the luminal pressure in the pharynx at the opening to the oesophagus,
is equal to atmospheric pressure, and the pressure at the opposite end of the oesophagus,
in the stomach is slightly greater than atmospheric pressure.
Therefore, pressure differences could tend to force both air (from above) and gastric contents (from below),
into the oesophagus.
This does not occur, however because both ends of the oesophagus are normally closed,
by the contraction of sphincter muscles.
A ring of skeletal muscles surrounds the oesophagus just below the pharynx,
and forms the upper oesophageal sphincter,
where as the smooth muscle in the last portion of the oesophagus form the lower oesophageal sphincter.
The oesophagus phase of swallowing begins with relaxation of the upper oesophageal sphincter.
Normally, in the absence of swallowing, this sphincter is closed.
This permits inhaled air to travel from the pharynx -
a structure shared by the digestive and respiratory systems - to the trachea.
Immediately after the food has passed, the sphincter closes again, the glottis opens and breathing resumes.
Once in the oesophagus, the food moves towards the stomach by peristalsis -
a progressive wave of muscle contractions that proceeds along the oesophagus,
compressing the lumen and forcing the food ahead.
Each oesophageal peristaltic wave takes about nine seconds to reach the stomach.
Swallowing can occur even when a person is upside down or in zero gravity (outer space),
because it is not primarily gravity but the peristaltic wave that moves the food to the stomach.
The lower oesophageal sphincter opens and remains relaxed throughout the period of swallowing,
allowing the arriving food to enter the stomach.
After the food passes, the lower oesophageal sphincter closes,
resealing the junction between the oesophagus and the stomach.
The act of swallowing is a neural and muscular reflex coordinated by a group of brain stem nuclei,
collectively called the swallowing system.
Both skeletal and smooth muscles are involved,
so the swallowing centre must direct the efferent activity in both somatic nerves (to skeletal muscle),
and autonomic nerves (to smooth muscle).
Simultaneously, afferent fibres from receptors in the oesophageal wall send information,
to the swallowing centre; this can alter the afferent activity.
For example, if a large food bolus does not reach the stomach during the initial peristaltic wave,
the maintained distension of the oesophagus by the bolus activates receptors that initiate reflexes,
causing repeated waves of peristaltic activity (secondary peristalsis).
The ability of the lower oesophageal sphincter to maintain a barrier,
between the stomach and the oesophagus when swallowing is not occurring,
is aided because the last portion of the oesophagus lies below the diaphragm,
and subject to the same abdominal pressures as the stomach.
In other words, if the pressure in the abdominal cavity increases, for example,
during cycles of respiration or contraction of the abdominal muscles,
the pressure on both the gastric contents and the terminal segment of the oesophagus,
are increased together.
This prevents the formation of a pressure gradient between the stomach and oesophagus,
that could force the stomach’s contents into the oesophagus.
The lower oesophageal sphincter undergoes brief periods of relaxation not only during a swallow,
but also in the absence of a swallow.
During this period of relaxation, small amounts of the acid contents from the stomach,
normally reflux into the oesophagus.
The acid in the oesophagus triggers a secondary peristaltic wave,
and also stimulates increased salivary secretion, which helps to neutralise the acid.
Some people have less efficient lower oesophageal sphincter,
resulting in repeated episodes of gastric contents moving into the oesophagus,
a condition called acid reflux.
Smoking and ingestion of alcohol and caffeine can contribute to this problem.
When acid reflux occurs, the hydrochloric acid from the stomach irritates the oesophagus walls,
producing pain known as heartburn,
(because the pain subjectively appears to be located in the area of the heart).
It can also cause coughing and irritation of the larynx in the absence of any oesophageal symptoms.
Gastroesophageal reflux can occur after a large meal, which can sufficiently increase,
the pressure in the stomach to force acidic gastric contents into the oesophagus.
This is more likely to occur in individuals who have increased pressure in the abdominal cavity - for example,
in individuals who are obese with significant deposits of abdominal fat or in the later stages of pregnancy.
The stomach.
Food particles that enter the stomach are thoroughly mixed with gastric secretions to form the solution,
defined earlier as chyme.
Chyme contains molecular fragments, proteins, and polysaccharides, droplets of fat: and ions, water,
and various other molecules ingested in the food.
Virtually none of these ions or molecules, except water can cross the epithelium of the gastric wall,
and thus little absorption of nutrients occurs in the stomach.
In addition to playing a role in the breakdown of proteins, the stomach functions as a storage vessel,
that periodically empties some chyme into the small intestine,
at a rate that favours the complete digestion and absorption of a meal.
Anatomy.
The oesophagus opens into the body of the stomach, the upper most part which is referred to as the fundus.
The lower portion of the stomach, the antrum, has a thicker layer of smooth muscle,
and is responsible for mixing and grinding the stomach contents.
At the junction between the antrum and the small intestine is a ring of contractile smooth muscles,
called pyloric sphincter.
The epithelium layer lining the stomach invaginate into the mucosa, forming many tubular glands,
the secretions of which will be described next.
Secretion of the stomach.
The cells at the opening of the gastric glands secrete a protective coating of mucus and HCO3- .
Lining the walls of the glands are parietal cells, which secrete acid and intrinsic factor, and chief cells,
which secrete pepsinogen.
Intrinsic factor is a protein that binds and allows the absorption of ingested vitamin B12.
Thus each of the major exocrine secretions of the stomach - mucus, acid, and pepsinogen -
is secreted by a difference cell type.
The unique invaginations of a apical membrane of parietal cells are called canaliculi :
these increase the surface area of the parietal cells, thereby maximising secretion into the lumen,
of the stomach.
This again illustrates the general principle of physiology that structure (increased surface area),
is a determinant of function (efficient secretion).
The gastric glands in the antrum also contain entero-endocrine cells called G cells, which secrete gastrin.
In addition, ECL cells, which release the paracrine substance histamine and other cells called D cells,
which secrete the polypeptide somatostatin, are scattered throughout the tubular glands,
or in surrounding tissue: both of these substances contribute to the regulation of acid secretion,
by the stomach.
The acidic environment in the stomach alters the ionisation of polar molecules,
leading to the denaturation of protein.
This exposes more sites for digestive enzymes to breakdown the proteins,
and disrupts the extra cellular network of connective tissue proteins that form the framework of the tissues, (example, muscle) in food.
Polysaccharides and fat are major food components that are not dissolved to a significant extent by the acid.
The high acidity also kills most of the bacteria that enters along with the food.
The process is not completely effective, and some bacteria survive to colonise and multiply,
in the remainder of the GI tract, particularly in the large intestine.
Hydrochloric acid production and secretion.
The stomach secretes about 2 litres of hydrochloric acid per day.
The concentration of H+ in the lumen of the stomach may reach greater than 150 Millimolar,
which is 1 to 3 million times greater than the concentration in the blood.
This requires an efficient production mechanism to generate large numbers of hydrogen ions.
The origin of hydrogen ions is CO2 in the parietal cell, which contains the enzyme carbonic anhydrase.
Carbonic anhydrase catalysis the reaction between CO2 with water to produce carbonic acid,
which disassociates to H+ and HCO3- .
Primary active H+/ K+ ATPase pumps in the apical membrane of the parietal cell pump hydrogen ions,
into the lumen of the stomach.
This primary active transporter also pumps K+ into the cell, which then leaks back into the lumen,
HCO3- is moved across the basolateral membrane and into the capillaries in exchange for CL-,
which maintains electroneutrality.
Removal of the end products (H+and HCO3- ) of this reaction enhances the rate of the reaction,
by the law of mass action.
In this way, production and secretion of H+ are coupled.
Increased acid secretion results from the transfer of H+/K+ ATPase proteins,
from the membranes of intracellular vesicles to the plasma membrane by fusion of these vesicles,
with the apical membrane, thereby increasing acid secretion: Gastrin (a gastric hormone),
acetylcholine (ACh, a neurotransmitter), and histamine (paracrine substance).
By contrast somatostatin - another paracrine substance - inhibits acid secretion.
Parietal cell membranes contain receptors for all four of these molecules.
This illustrates the general principle of physiology that most physiological functions - in this case,
the secretion of H+ into the stomach lumen - are controlled by multiple regulatory systems,
often working in opposition.
These chemical messengers not only act directly on the parietal cells,
but also influence each other’s secretion.
For example, histamine markedly potentiates the response to the other two stimuli, gastrin and ACh,
both stimulate histamine secretion.
During a meal, the rate of acid secretion increases markedly,
as stimuli arising from the cephalic and gastric phases alter the release of ACh from the plexus neurons, gastrin from the gastrin releasing G cells, and histamine from the ECL cells.
Once food has reached the stomach, the gastric phase stimuli -
distension from the volume of ingested material and the presence of peptides and amino acids,
released by the digestion of luminal proteins - produce a further increase in acid secretion.
These stimuli use some of the same neural pathways used during the cephalic phase.
Neurons in the mucosa of the stomach respond to these luminal stimuli and send action potentials,
to the cells in the enteric nervous system, which in turn can relay signals to the gastrin-releasing cells,
histamine-releasing cells, and parietal cells.
In addition, peptides and amino acids can act directly on the gastrin releasing enteroendocrine cells,
to promote gastrin secretion.
The concentration of acid in the gastric lumen is itself an important determinant of the rate of acid secretion, because H+(acid) directly inhibits gastrin secretion.
It also stimulates the release of somatostatin from D cells in the stomach wall.
Somatostatin then acts on the parietal cells to inhibit acid secretion;
it also inhibits the release of gastrin and histamine.
The net result is a negative feedback control of acid secretion.
As the contents of the gastric lumen become more acidic, the stimuli that promotes acid secretion decrease.
Increasing the protein content of a meal increases acid secretion for two reasons.
First, protein ingestion increases the concentration of peptides in the lumen of the stomach.
These peptides, stimulate acid secretion through their actions on gastrin.
The second reason is more complicated and reflects the effects of proteins on luminal acidity.
During the cephalic phase, before food enters the stomach,
the H+ concentration in the lumen increases because there are few buffers present to bind the secreted H+.
Thereafter, the rate of acid secretion decreases because high acidity reflexively inhibits acid secretion.
The protein in food is an excellent buffer, so as it enters the stomach,
the H+ concentration decreases as H+ binds to proteins to denature them.
This decrease in acidity removes the inhibition of acid secretion.
The more protein in the meal, the greater the buffering of acid and the more acid secreted.
We now come to intestinal phase of control of acid secretion -
reflexes in which stimuli in the early portion of the duodenum trigger inhibition of gastric and acid secretion.
This inhibition is beneficial because digestive activity in the small intestine,
is strongly inhibited by acidic solutions.
These reflexes limit gastric acid production when the H+ concentration in the duodenum,
increases during the entry of chyme from the stomach.
Acid, distension, hypertonic solutions, and solutions containing amino acids and fatty acids,
in the small intestine reflexively inhibit gastric acid secretion in the stomach.
The extent to which gastric acid secretion is inhibited during the intestinal phase varies,
depending upon the amounts of these substances in the intestine.
The net result is the same - the secretory activity of the stomach is balanced,
with the digestive and absorptive capacities of the small intestine.
The inhibition of gastric secretion during the intestinal phase is mediated by short and long neural reflexes, and by hormones that inhibit acid secretion.
These pathways influence the four signals that directly control gastric acid secretion - ACh, gastrin,
histamine, and somatostatin.
The hormones released by the intestinal tract that reflexively inhibit gastric activity,
are collectively called enterogastrones and include secretin and CCK.
Pepsin secretion.
Pepsin is an enzyme that is secreted by chief cells in the form of an inactive precursor called pepsinogen.
Exposure to low pH in the lumen of the stomach activates a very rapid autocatalytic process.
in which pepsin is produced from pepsinogen.
The synthesis and secretion of pepsinogen, followed by intraluminal activation to pepsin,
provide an example, of a process that occurs with many other secreted proteolytic enzymes in the GI tract.
These enzymes are synthesised and stored intracellularly in inactive forms,
collectively referred to as zymogens.
Consequently, zymogens do not act on proteins inside the cells that produce them,
thereby protecting the cell from proteolytic damage.
Pepsin is active only in the presence of high H+ concentration (low pH).
It is inactivated when it enters the small intestine,
where HCO3- secreted by the small intestine and pancreas neutralises the H+.
The primary pathway for stimulating pepsinogen secretion,
is input to the chief cells from the enteric nervous system.
During the cephalic, gastric, and intestinal phases,
most of the factors that stimulate or inhibit acid secretion exert the same effect on pepsinogen secretion.
Thus pepsinogen secretion parallels acid secretion.
Pepsin is not essential for protein digestion because,
in its absence as occurs in some pathological conditions,
proteins can be digested by enzymes in the small intestine.
However, pepsin accelerates protein digestion,
and normally accounts for about 20% of total protein digestion.
It is also important in the digestion of collagen contained in the connective tissue matrix of meat.
This is useful because it helps shred meat into smaller, more easily processed pieces,
with greater surface area for digestion.
We will now discuss to the patterns of smooth muscle contraction that occur in the stomach,
and will see that the stomach’s motility is regulated in a way that is similar to how its secretion is regulated.
Gastric motility.
A empty stomach has a volume of only about 50ml,
and a luminal diameter of only slightly larger than that of the small intestine.
When a meal is swallowed, the smooth muscle in the stomach relaxes before the arrival of food,
allowing the stomach’s volume to increase as much as 1.5 litres with little increase in pressure.
This receptor relaxation is mediated by the parasympathetic nerves,
innervating the stomach’s enteric nerve plexuses,
with coordination provided by afferent vagal input from the stomach.
and by efferent input from the swallowing centre in the brain.
Nitric oxide and serotonin released by enteric neurons mediate this relaxation.
As in the oesophagus the stomach produces peristaltic ways in response to the arriving food.
Each wave begins in the body of the stomach and produces only a ripple as it proceeds towards the antrum:
this contraction is too weak to produce much mixing of the luminal contents with acid and pepsin.
As the wave approaches the larger mass of wall muscle surrounding the antrum,
however, it produces a more powerful contraction,
which both mixes the luminal content and closes the pyloric sphincter.
The pyloric sphincter muscles contract upon arrival of a peristaltic wave.
As a consequence of the sphincter closing, only a small amount of chyme,
is expelled into the duodenum with each wave.
Most of the astral contents are forced backward toward the body of the stomach.
The backward motion of chyme, called the retropulsion,
generates strong shear forces that help to disperse the food particles and improve mixing of the chyme.
The lower oesophageal sphincter prevents the retrograde movement of stomach contents,
from entering the oesophagus.
What is responsible for producing gastric peristaltic waves?
Their rate, about 3 per minute, is generated by pacemaker cells in the longitudinal smooth muscle layer.
These smooth cells undergo spontaneous depolarisation - repolarisation 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 the overlying circular muscle layer.
In the absence of neural or hormonal input,
these depolarisation are too small to cause significant contractions.
Excitatory neurotransmitters and hormones act upon the smooth muscle,
to further depolarise the membrane, thereby bringing it closer to threshold.
Action potentials may be generated at the peak of the slow wave cycle if threshold is reached,
causing larger contractions.
The number of action potentials fired with each wave determines the strength of the muscular contraction.
Therefore, whereas the frequency of contraction is determined by the intrinsic basic electrical rhythm,
and remains essentially constant, the force of the contraction - and,
consequently the amount of gastric emptying per contraction -,
is determined by neural and hormonal input to the antral smooth muscle.
The initiation of reflexes that control gastric motility depends on the contents,
of both the stomach and the small intestine.
The factors that regulate acid secretion can also alter gastric motility.
For example,
gastrin in sufficiently high concentrations increases the force of the antral smooth muscle contractions.
Distension of the stomach also increases the force of the antral contractions,
through long and short reflexes triggered by the mechanoreceptors in the stomach wall.
Therefore, after a large meal, the force of initial stomach contractions is greater,
which results in greater emptying per contraction.
In contrast, gastric emptying is inhibited by distension of the duodenum, the presence of fat,
high acidity (low pH), or hypertonic solutions in the lumen of the duodenum.
This reflex is referred to as enterogastric reflex.
These are the same factors that inhibit acid and pepsin secretion in the stomach.
Fat is the most potent of these chemical stimuli.
This prevents over filling of the duodenum.
The rate of gastric emptying has significant clinical implications,
particularly when considering what food type is eaten with oral medications.
A meal rich in fat content tends to slow oral drug absorption due to the delay of the drug,
entering the small intestine through the plyloric sphincter.
A hypertonic solution in the duodenum is one of the stimuli inhibiting gastric emptying.
This reflex prevents the fluid in the duodenum from becoming too hypertonic.
It does so by slowing the rate of chyme entry, thereby decreasing the delivery rate of large molecules,
that can be broken down into many smaller molecules by enzymes in the small intestine.
Autonomic neurons to the stomach can be activated by the CNS independently of the reflexes,
originating in the stomach and duodenum, and can influence gastric motility.
An increase in parasympathetic activity increases gastric motility,
whereas an increase in sympathetic activity decreases motility.
Via these pathways, pain and emotions can alter motility; however,
different people show different GI responses to apparently similar emotional states.
The small intestine.
Anatomy.
The macro and microscopic structure of the wall of the small intestine is particularly elaborate.
The circular folds are covered with fingerlike projections called villi.
The surface of each villus is covered with a layer of epithelial cells,
whose surface membranes forms small projections called microvilli or brush border.
Interspersed between these absorptive epithelial cells are goblet cells that secret mucus into the lumen,
where it lubricates and protects the inner surface of the wall of the small intestine.
The combination of circular folds, villi, and microvilli increases the small intestine’s total surface area,
about 600 folds over that of a flat surfaced tube having the same length and diameter.
The human small intestine’s total surface area is about 250 to 300 square meters,
roughly the area of a tennis court.
This is a dramatic example of the general principle of physiology that structure is a determinant of function;
in this case, the greatly increased surface area of the small intestine maximises its absorptive capacity.
Just as the folding of the cerebral cortex provides much larger number of neurons in the cranium,
and the large surface area of the alveoli enhances gas exchange in the lungs,
the large surface area provided by the morphology of the small intestine,
allows for the highly efficient digestion and absorption of nutrients.
The centre of each intestinal villus is occupied by a single blind ended lymphatic -
a lacteal - and a capillary network.
Most of the fat absorbed in the small intestine enters the lacteals.
Material absorbed by the lacteals reaches the general circulation,
by eventually emptying from the lymphatic system into large veins,
through a structure called the thoracic duct.
The small intestine is divided into three segments:
An initial short segment, the duodenum, is followed by a jejunum and then by the longest segment,
the ileum.
Normally, most of the chyme entering from the stomach is fully digested,
and absorbed in the first quarter of the small intestine in the duodenum and part of the jejunum.
Therefore, the small intestine has a very large reserve for the absorption of most nutrients;
removal of portions of the small intestine for disease doesn’t necessarily result in nutritional deficiencies,
depending on which part of the intestine is removed.
Moreover the remaining tissue can often increase its digestive and absorptive capacities,
to compensate in part for the removal of the diseased part.
The exocrine pancreas and liver connect to the small intestine via ducts,
and produce secretions essential to the function of the small intestine.
The pancreas is an elongated gland located behind the stomach.
A large, central pancreatic duct delivers exocrine secretion of the pancreas into the duodenum.
The liver, a large organ located in the upper right portion of the abdomen,
secretes bile into small ducts that join to form the common hepatic duct.
Between meals, secreted bile is stored in the gallbladder,
a small sac under the liver that branches from the common hepatic duct.
During a meal, the smooth muscles in the gallbladder wall are stimulated to contract,
causing a concentrated bile solution to flow down the common bile duct,
and be injected through the sphincter of Oddi into the duodenum.
Secretions.
Approximately 1500ml of fluid is secreted by the cells of the small intestine from the blood,
into the lumen each day.
The ion sodium plus is read as Na+.
Similarly other ions also can be misread.
One of the causes of water secretion into the lumen is that the intestinal epithelium at the base of the villi, secretes a number of ions - notable Na+, Cl- and HCO3- into the lumen, and water follows by osmosis.
The osmotic gradient is enhanced when chyme entering the small intestine from the stomach,
is hypertonic due to high concentration of solutes resulting from the breakdown,
of large food molecules into many more small molecules.
These secretions, along with mucus, lubricates the surface of the intestinal tract,
and help protect the epithelial cells from excessive damage by the digestive enzymes in the lumen.
Some damage to these cells still occurs,
so that the intestinal epithelium has one of the highest renewal rates of any tissue in the body.
In addition, the Na+ ions secreted into the tract drive secondary active transporters,
that absorb monosaccharides and amino acids from the lumen into the epithelial cells.
Pancreatic secretions.
The pancreas has both endocrine and exocrine functions,
but only the latter are directly involved in the gastrointestinal processes.
The exocrine portion of the pancreas secretes HCO3- and the number of digestive enzymes,
into the duodenum.
The enzymes are secreted by the cells called acinar cells.
HCO3- is secreted by the epithelial cells lining the pancreatic ducts.
The high acidity of the chyme coming from the stomach would inactivate the pancreatic enzymes,
in the small intestine if the acid were not neutralised by the HCO3- in the pancreatic fluid.
The pancreatic duct cells secrete HCO3- produced from CO2 and water,
into the duct lumen via a apical membrane Cl-/HCO3- exchanger,
while the hydrogen produced is exchanged for extracellular Na+ on the basolateral side of the cell.
The H+ enters the pancreatic capillaries to eventually meet-up in the venous blood containing the HCO3- ,
produced by the stomach during the generation of luminal H+.
As with many transport systems, the energy for secretion of HCO3-,
is ultimately provided by Na+/K+ ATPase pumps on the basolateral membrane.
Cl- normally does not accumulate within the cell because these ions are recycled into the lumen,
through the cystic fibrosis transmembrane regulator (CFTR).
Via a paracellular route, Na+ and water move in to the ducts,
due to the electro chemical gradient established by chloride movement through the CFTR,
that cause cystic fibrosis result in decreased pancreatic HCO3- secretion.
Further more, the lack of normal water movement into the lumen,
leads to the thickening of pancreatic secretions;
this can lead to clogging of the pancreatic ducts and pancreatic damage.
In fact, the cystic (cyst forming) and fibrotic (scaring)appearance of the diseased pancreas,
was the origin of the name of this disease.
Enzymes secreted by the pancreas digest fat, polysaccharides, proteins, and nucleic acids to fatty acids,
and monoglycerides, sugars, amino acids, and nucleotides, respectively.
The proteolytic enzymes are secreted in inactive forms (zymogens),
as described for pepsinogen in the stomach, and then activated in the duodenum.
Like pepsinogen, the secretion of zymogens protects pancreatic cells from autodigestion.
A key step in this activation is mediated by enterokinase,
which is embedded in the apical plasma membranes of the intestinal epithelial cells.
Enterokinase is a proteolytic enzyme that splits of the peptide from pancreatic trypsinogen,
forming the active enzyme trypsin.
Trypsin is also a proteolytic enzyme; once activated, it activates the other pancreatic zymogens,
by splitting of peptide fragments.
This activating function is in addition to the function of trypsin in digesting ingested protein.
The non proteolytic enzymes secreted by the pancreas (example, amylase and lipase),
are released in fully active form.
Pancreatic secretions increases during a meal, mainly as a result of stimulation of the pancreas,
by the hormones secretin and CCK released from enteroendocrine cells of the small intestine.
Secretin is the primary stimulant for HCO3-, where as CCK mainly stimulates acinar cell secretion.
Because the function of pancreatic HCO3- is to neutralise acid entering the duodenum from the stomach,
it is appropriate that the major stimulus for secretin release is increased acidity in the duodenum.
In analogous fashion, CCK stimulates the secretion of digestive enzymes,
including those for fat and protein digestion,
so it is appropriate that the stimuli for its release of fatty acids and amino acids in the duodenum.
Luminal acid and fatty acids also act on afferent neurons ending in the intestine wall,
initiating reflexes that act on the pancreas to increase both enzymes and HCO3- secretion.
In these ways, the organic nutrients in the small intestine initiate neural and endocrine reflexes,
that control the secretions involved in their own digestion.
Although most of the pancreatic exocrine secretions are controlled by stimuli,
arising from the intestinal phase of digestion,
cephalic and gastric stimuli also contribute by way of the parasympathetic nerves to the pancreas.
Thus the taste of food or the distension of the stomach by food will lead to increased pancreatic secretion.
This is an example of the feed forward process.
Bile formation and secretion.
As mentioned previously, exocrine secretions from the liver enter the small intestine,
and are beneficial for normal digestion.
We will discuss the liver’s exocrine functions that are directly related to the secretion of bile.
Bile contains HCO3-, cholesterol, phospholipids, bile pigments, and number of organic wastes,
and a group of substances collectively termed bile salts.
The HCO3-, like that from the pancreas, help neutralise acid from the stomach,
whereas the bile salts and phospholipids, solubilise dietary fat.
These fats would otherwise be insoluble in water,
and their solubilisation increases the rates at which they are digested and absorbed.
The other components of bile are extracted from blood and excreted as wastes.
The functional unit of the liver is the hepatic lobule.
Within the lobule are structure called portal triads that are composed of branches of the bile duct,
the hepatic and portal veins, and the hepatic artery.
Substances absorbed from the small intestine windup in the hepatic sinusoid,
either to reach the vena cava via the central vein, are taken up by the hepatocytes (liver cells).
In which they can be modified.
Hepatocytes can rid the body of substances by secretion into the bile canaliculi,
which converts to form the hepatic bile duct.
The most important digestive components of bile are the bile salts.
During the digestion of a fatty meal, most of the bile salts entering the intestinal tract,
via the bile are absorbed by specific Na+ coupled transporters in the ileum,
the last segment of the small intestine.
The absorbed bile salts are returned via the portal vein to the liver,
where they are once again secreted into the bile.
Uptake of bile salts from portal blood into hepatocytes is driven by secondary active transport,
coupled to Na+.
This recycling pathway from the liver to the intestine and back to the liver,
is known as enterohepatic circulation.
The small amount (5%) of the bile salts escapes this recycling and is lost in the feces,
but the liver synthesises new bile salts from cholesterol to replace it.
During the digestion of a large meal, the entire bile content of the body may be recycled several times,
via the enterohepatic circulation.
In addition to synthesising the bile salts from cholesterol, the liver also secretes cholesterol from the blood, into the bile.
Bile secretion, followed by bile excretion in the feces,
is one of the ways of maintaining cholesterol homeostasis in the blood.
It is also the process by which cholesterol lowering drugs work.
Dietary fibre also sequesters bile, thereby lowering cholesterol in the blood.
This occurs because the sequestered bile salts escape the enterohepatic circulation.
Therefore, the liver must synthesise new cholesterol, or remove it from the blood,
or both to produce more bile salts.
Cholesterol is insoluble in water, and its solubility in bile is achieved by its incorporation,
into tiny fat droplets called micelles.
In blood, cholesterol is incorporated into lipoproteins.
Gallstones, consists of precipitated cholesterol.
Bile pigments are substances formed from the heme portion of hemoglobin,
when old or damaged erythrocytes are broken down in the spleen or liver.
The predominant bile salt is bilirubin, which is extracted from the blood by hepatocytes,
and actively secreted into the bile.
Bilirubin is yellow and contributes to the colour of bile.
During their passage through the intestinal tract, some of the bile pigments are absorbed into the blood,
and are eventually excreted in the urine, giving urine its yellow colour.
After entering the intestinal tract, some bilirubin is modified by bacterial enzymes,
to form the brown pigments that give feces their characteristic colour.
The components of bile are secreted by two different cell types.
The bile salts, cholesterol, phospholipids, and bile pigments are secreted by hepatocytes,
whereas most of the HCO3- rich solution is secreted by the epithelial cells lining the bile ducts.
Secretion of HCO3- rich solution by the bile ducts, just like the secretion by the pancreas,
is stimulated by secretin in response to the presence of acid in the stomach.
Although bile secretion is greatest just during or after a meal, the liver is always secreting some bile.
Between meals the sphincter of Oddi remains closed and dilute bile is shunted into the gallbladder,
where the organic components of bile become concentrated,
as some NaCl and water are absorbed into the blood.
Shortly after the beginning of a fatty meal, the sphincter of Oddi relaxes and the gallbladder contracts,
discharging concentrated bile into the duodenum.
The signal for gallbladder contraction and sphincter relaxation is the intestinal hormone CCK,
- appropriately so, because the presence of fat in the duodenum,
is a major stimulus for the hormones release.
It is from this ability to contract the gallbladder, that cholecystokinin received its name: chole, ‘bile’,;
cysto ‘bladder’ and kinin ‘move’.
Digestion and absorption in the small intestine.
While chyme from the stomach is throughly mixed with the secretions from the small intestine, pancreas,
and liver, the digestion and absorption of a meal begins in earnest.
Most of the digestion and absorption of nutrients occurs in the small intestine.
It follows the general principle of physiology that controlled the exchange of materials,
occurs between compartments (in this case, from the lumen of the small intestine to the blood and lymph), and across cellular membranes (of the cells lining the GI tract),
we will discuss the major mechanisms for carbohydrate, protein and fat digestion and absorption :
Nuclei acids are handled in similar general ways and are not discussed.
Carbohydrate.
The average daily intake of carbohydrates is about 200-300 grams.
This represents about half the daily intake of calories.
About two thirds of this carbohydrate is the plant polysaccharide starch,
and most of the remainder consists of disaccharides sucrose (table sugar) and lactose (milk sugar).
Ingestion of the monosaccharides fructose is fairly low on a diet of whole foods,
but it can be significant when the diet includes processed food sweetened with high fructose corn syrup.
Cellulose and certain other complex polysaccharides found in vegetable matter -,
referred to as dietary fibre - or not broken down by enzymes in the small intestine,
and pass on to the large intestine, where they are partially metabolised by bacteria.
The digestion of starch by salivary amylase begins in the mouth,
but accounts for only a small fraction of the total starch digestion.
It continues very briefly in the upper part of the stomach before gastric acid inactivates the amylase.
Most (95% or more) starch digestion is completed in the small intestine by pancreatic amylase.
The products of both salivary and pancreatic amylase are the disaccharide maltose and a mixture of short,
branched chain of glucose molecules.
These products, along with ingested sucrose and lactose, are broken down into monosaccharides,
- glucose, galactose, and fructose - by enzymes located on the apical membranes,
of the small intestine epithelial cells (brush border).
These monosaccharides are then transported across the intestinal epithelium into the blood.
Fructose enters the epithelial cells via one type of a family of monosaccharide transporters,
called glucose transporters (GLUTS), whereas glucose and galactose undergo secondary active transport, coupled to Na+ via a sodium-glucose co-transporter (SGLT).
These monosaccharides then leave the epithelial cells and enter the interstitial fluid,
by way of facilitated diffusion via various GLUT proteins in the basolateral membranes of the epithelial cells.
From there, the monosaccharides diffuse into the blood through capillary pores.
Most ingested carbohydrates are digested and absorbed within the first 20% of the small intestine.
Proteins.
A healthy average sized adult requires about 40 to 60 grams of protein to supply essential amino acids,
and replace the nitrogen contained in amino acids that are metabolised to urea.
A typical diet contains 60 to 90 grams of protein per day.
This represents about one sixth of the average daily calorie intake.
In addition, a large amount of protein, in the form of mucus,
is secreted into the GI tract or enters it via the depth and disintegration of epithelial cells.
Regardless of the source, most of the protein in the lumen is broken down into dipeptides,
tripeptides and amino acids, all of which are absorbed by cells of the small intestine.
Proteins are first partially broken down to peptide fragments in the stomach by the enzyme pepsin.
Further breakdown is completed in the small intestine by the enzyme trypsin and chymotrypsin,
the major active forms of proteases secreted by the pancreas.
These peptide fragments can be absorbed if they are small enough or further digested to free amino acids,
by carboxylpeptidases (additional proteases secreted by the pancreas) and amino peptidases,
located on the apical membranes of the small intestine epithelial cells.
These last two enzymes split off amino acids from the carboxyl and amino ends of peptide fragments,
respectively.
At least 20 different peptidases are located in the apical membrane (that is, the microvilli),
of the epithelial cells, with various specificities from the peptide bonds they attack.
Most of the products of protein digestion are absorbed as short chains of two or three amino acids,
by secondary active transport coupled to the H+ gradient.
The absorption of small peptides contrast with carbohydrate absorption, in which amino acids, by contrast,
enter the epithelial cells by secondary active transport coupled to Na+ .
There are many different amino acid transporters that are specific to different amino acids.
Within the cytosol of the epithelial cells, the dipeptides and tripeptides are hydrolysed to amino acids;
these, along with free amino acids that entered the cells, then leave the cell and enter the interstitial fluid, through facilitated-diffusion transporters in the basolateral membranes.
As with carbohydrates, protein digestion and absorption are largely completed,
in the beginning portion of the small intestine.
Very small amounts of intact proteins are able to cross the intestinal epithelium,
and gain access to the intestinal fluid.
They do so by a combination of endocytosis and exocytosis.
The absorptive capacity for intact proteins is much greater in infants than in adults,
and antibodies (proteins involved in the immunologic immune system of the body),
secreted into the mother’s milk can be absorbed intact by the infant,
providing some immunity until the infants immunity system matures.
Fats.
The average daily intake of lipids is 70 to 100 grams per day, mostly in the form of fats (triglycerides).
This represents about one third of the average daily calorie intake.
Triglyceride digestion occurs to a very limited extent in the mouth and stomach, and it predominantly occurs in the small intestine.
The major digestive enzyme in this process is pancreatic lipase,
which catalysis the splitting of bonds linking fatty acids to the first and third carbon atoms of glycerol,
producing two fatty acids and a monoglyceride.
The lipids in the ingested food are insoluble in water, and aggregate into large lipid droplets,
in the upper portion of the stomach.
This is like a mixture of oil and vinegar after shaking.
Because pancreatic lipase is a water soluble enzyme, its digestive action in the small intestine,
can take place only at the surface of the lipid droplet.
Therefore, if most of the ingested fat remained in large lipid droplets,
the rate of triglyceride would be very slow because of the small surface area-to-volume ratio,
of these big droplets.
The rate of digestion is, substantially increased by division of large lipid droplets,
into many very small droplets, each about 1 millimetre in diameter,
thereby increasing their surface area accessibility to lipase action.
This process is known as emulsification, and the resulting suspension of small lipid droplets,
is called an emulsion.
The emulsion of fat requires:
- mechanical disruption of the large lipid droplets into smaller droplets.
- a emulsifying agent which acts to prevent the smaller droplets from reaggregating back into large droplets.
The mechanical disruption is provided by the motility of the GI tract,
occurring in the lowest portion of the stomach and in the small intestine,
which grinds and mixes the luminal contents.
Phospholipids in food, along with phospholipids and bile salts secreted in the bile,
provide the emulsifying agents.
Phospholipids are amphipathic molecules consisting of two non polar fatty acid chains attached to glycerol,
with a charged phosphate group located in the glycerol’s third carbon.
Bile salts are formed from cholesterol in the liver and are also amphipathic.
The non polar portions of the phospholipids and bile salts,
associate with the non polar interior of the lipid droplets,
leaving the polar portions exposed to the water surface.
There, the polar regions repel other lipid droplets that are similarly coated with these emulsifying agents,
thereby preventing there reaggregation into larger fat droplets.
The coating of the lipid droplets with these emulsifying agents, however,
impairs the accessibility of the water soluble pancreatic lipase to its lipid substrate.
To overcome this problem the pancreas secrete a protein known as colipase,
which is amphipathic and lodges on the lipid droplet surface.
Colipase binds the lipase enzyme, holding it on the surface of the lipid droplet.
Although emulsification speeds up digestion,
absorption of the water insoluble products of the lipase reaction would be still very slow,
if it were not for a second action of the bile salts,
the formation of micelles which are similar in structure to emulsion droplets,
but much smaller-only four to seven nanometers in diameter.
Micelles consists of bile salts, mono glycerides and phospholipids all clustered together,
with the polar ends of each molecule oriented towards the micelles surface,
and the non polar portions forming the micelles core.
Also included in the core of the micelles are small amounts of fat soluble vitamins and cholesterol.
How do micelles increase absorption?
Although fatty acids and mono glycerides have a extremely low solubility in water,
a few molecules do exist in solution,
and are free to diffuse across the lipid portion of the apical plasma membrane,
of the epithelial cells lining the small intestine.
Micelles, containing the products of fat digestion,
are in equilibrium with small concentration of fat digestion products that are free in solution.
Thus, micelles are continuously breaking down and reformed.
As the luminal concentration of free lipids decrease because of their diffusion into epithelial cells,
more lipids are released into the free phase from micelles as they begin to break down.
Meanwhile, the process of digestion, which is still ongoing,
provides additional small lipids that replenish the micelles.
In this way, micelles provide a means of keeping most of the insoluble fat digestion products,
in small soluble aggregates while at the same time replenishing the small amount of products in solution,
that are free to diffuse into the intestinal epithelium.
Note that it is not the micelle that is absorbed but rather,
the individual lipid molecules released from the micelles.
You can think of micelles as a “holding station” for small, non soluble lipids,
releasing their contents slowly to prevent the lipids from coming out of solution,
while permitting digestion to continue unabated.
Although fatty acids and mono glycerides enter epithelial cells from the intestinal lumen,
triglycerides are released on the other side of the cell into the interstitial fluid.
In other words, during their passage through the epithelial cells,
fatty acids and mono glycerides are re-synthesized into triglycerides.
This occurs in the smooth endoplasmic reticulum, when the enzymes for triglyceride synthesis are located.
The process decreases the concentration of cytosolic free fatty acids and mono glycerides,
and thereby maintains a diffusion gradient for these molecules into the cell from the intestinal lumen.
The re-synthesized fat aggregates into small droplets coated with amphipathic proteins,
that perform an emulsifying similar to that of bile salts.
The exit of these fat droplets from the cell follows the same pathway as a secreted protein.
Vesicles containing the droplet pinch off the endoplasmic reticulum,
are processed through the Golgi apparatus, and eventually fuse with the plasma membrane,
releasing the fat droplet into the interstitial fluid.
These one micron diameter, extracellular fat droplets are known as chylomicrons.
Chylomicrons contain not only triglycerides but other lipids (phospholipids, cholesterol,
and fat soluble vitamins) that are being absorbed,
by the same process that led to fatty acid and monoglyceride movement,
into the epithelial cells of the small intestine.
The chylomicrons released from the epithelial cells pass into lacteals -
lymphatic vessels in the intestinal villi rather than into the blood capillaries.
The chylomicrons cannot enter the blood capillaries because the basement membrane,
(an extra cellular glycoprotein layer) at the outer surface of the capillary,
provides a barrier to the diffusion of large chylomicrons.
In contrast the lacteals have a large course between their endothelial cells,
that allow the chylomicrons to pass into the lymph.
Briefly, the amphipathic proteins coating chylomicrons keep the aggregate soluble in the blood.
These proteins are later recognised by receptors proteins in adipose tissue,
where the triglycerides will be stored.
Vitamins.
Vitamins are small organic molecules necessary for the healthy functioning of the body.
They do not require digestion, but their absorption occurs predominantly in the small intestine.
The fat soluble vitamins, A,D,E and F - follow the same pathway for fat absorption.
They are solubilised in micelles; thus, any interference with the secretion of bile,
or the action of bile salts in the intestine decreases the absorption of fat soluble vitamins.
With one exception, water soluble vitamins are absorbed by diffusion or mediated transport.
The exception, vitamin B12, is a very large charged molecule.
To be absorbed, vitamin B12, then binds to specific sites on the epithelial cells,
in the lower portion of the ileum, where vitamin B12, is absorbed by endocytosis.
Vitamin B12 is required for erythrocyte formation.
Water and minerals.
Water is the most abundant substance in chyme.
Approximately 8000ml of water enters the small intestine each day,
but only 1500ml passes on to the large intestine.
Small amounts of water are absorbed in the stomach, but the stomach has a much smaller surface area, available for diffusion and lacks the solute absorbing mechanisms that create the osmotic gradients,
necessary for net water absorption.
The epithelial membranes of the small intestine are very permeable to water,
and net water diffusion occurs across the epithelium whenever a water concentration difference,
is established by the active absorption of solutes .
Na+ accounts for much of the actively transported solute, because it is such an abundant solute in chyme.
Na+ absorption is a primary active transport process - using Na+/K+ - ATPase pumps -,
and similar to that for renal tubular Na+ and water reabsorption.
Cl- and HCO3- are absorbed with the Na+ and contribute another large fraction of the absorbed solute.
Other minerals present in smaller concentrations, such as potassium, magnesium, phosphate,
and calcium ions, are also absorbed, as trace elements such as iron, zinc, and iodine.
Absorption pathways.
Nutrients absorbed across the intestinal epithelium enter circulating blood by two different pathways.
Fats and other fat soluble nutrients first enter the lymphatic system.
Lymph vessels from the small intestine, as from everywhere else in the body,
eventually converge and empty into a large vein near the heart.
Chylomicrons then circulate throughout the bloodstream,
and deliver lipids and fat soluble vitamins to all body cells.
By contrast, all other absorbed nutrients move directly from intestinal capillaries,
and from there the blood flows into the veins.
The venous drainage from the small intestine - as well as the large intestine, pancreas,
and portions of the stomach - does not empty directly into the inferior vena cava but passes first,
via the hepatic portal vein, to the liver.
In the liver, the blood flows through a second capillary network,
before leaving the liver to return to the heart.
Because of this portal circulation, material that is absorbed into the capillaries,
from the abdominal organs can be processed by the liver before entering the general circulation.
This includes the products of carbohydrate and protein digestion,
as well as water, minerals, and water soluble vitamins.
In addition to delivery nutrients to the liver, the hepatic portal system has additional functional significance.
It delivers the pancreatic hormones insulin and glucagon to the liver,
where they regulate the metabolic processing of nutrients.
During the processing of a meal, parietal cells add excess HCO3- to blood leaving the stomach,
and pancreatic duct cells add excess H+ to blood leaving the pancreas.
When blood from these two organs meet in the hepatic portal vein, normal pH balance is restored.
Finally the hepatic portal vein system is important because the liver contains enzymes,
that can metabolise (detoxify) harmful compounds that may have been ingested and absorbed,
thereby greatly reducing their entry into the systemic circulation.
The relationship between the lymphatic system, the circulatory system,
and the absorptive surface of the GI tract, emphasises the general principle of physiology,
that there is coordination between the function of different organisms.
One must understand the distribution of blood flow to the GI tract and lymphatic drainage from the GI tract, to appreciate its huge absorptive and secretory capacity.
Motility of the small intestine.
The motility of the small intestine, brought about by the smooth muscles in its walls,
performs 3 major functions.
- mixes the luminal contents with the various secretions.
- brings the contents into contact with the epithelial surface where absorption takes place.
- slowly advances the luminal material toward the large intestine;
because most substances are absorbed in the small intestine, only small quantities of water,
ions and undigested material pass on to the large intestine.
In contrast to the peristaltic waves that sweep over the stomach,
the most common motion in the small intestine during digestion of a meal is a stationary contraction,
and relaxation of the intestinal segments, with little apparent net moment toward the large intestine.
Each contracting segment is only a few centimetres long, and the contraction lasts a few seconds.
The chyme in the lumen of a contracting segment is forced both forward and backward in the intestine.
This rhythmic contraction and relaxation of the intestine, known as segmentation,
produces a continuous division and subdivision of the intestinal contents,
throughly mixing the chyme in the lumen and bringing it into contact with the intestinal wall.
These segmenting movements are initiated by electrical activity generated by pacemaker cells,
in the circular smooth muscle layer.
As with the slow waves in the stomach, this intestinal basic electrical rhythm produces oscillations,
in the smooth muscle membrane potential.
If threshold has reached, action potentials are triggered that increase muscle contraction.
The frequency of segmentation is set by the frequency of the intestinal basic electrical rhythm:
unlike the stomach, however, which normally has a single rhythm (3 per minute),
the intestinal rhythm varies along the length of the intestine,
each successive region having a slightly lower frequency then the one above.
For example, segmentation in the duodenum occurs at a frequency of 12 contractions per minute,
whereas the last portion of the ileum, the rate is only 9 contractions per minute.
This temporal pattern of segmentation produces a slow migration of the intestinal contents,
towards the large intestinal because more chyme is forced towards the large intestine,
on average, then in the opposite direction.
The intensity of the segmentation can be altered by hormones, the enteric nervous system,
an autonomic nerves; parasympathetic activity increases the force of contraction,
and sympathetic simulation decreases it.
Thus, the cephalic phase stimuli, as well as emotional state, can alter intestinal motility.
As is true for the stomach, these inputs produce changes in the force of smooth muscle contraction,
but do not significantly change the frequency of the basic electrical rhythms.
After most of a meal has been absorbed, the segmenting contractions cease,
and are replaced by a peristaltic activity known as MMC.
Beginning in the lower portion of the stomach, repeated waves of peristaltic activity travel about 2 feet,
along the small intestine and die out.
The next MMC starts slightly farther down in the small intestine so that peristaltic activity,
slowly migrates down the small intestine.
By the time the MMC reaches the end of the ileum, new waves are beginning in the stomach,
and the process repeats.
The MMC moves any undigested material still remaining in the small intestine,
and also prevents bacteria remaining in the small intestine long enough to grow and multiply extensively,
in diseases characterised by an aberrant MMC bacterial overgrowth can become a major problem.
Upon the arrival of a meal in the stomach, the MMC rapidly ceases in the intestine,
and is replaced by segmentation.
An increase in the plasma concentration of the intestinal hormone motility is thought to initiate the MMC.
Feeding inhibits the release of motilin;
motilin stimulates MMC’s via both the enteric and autonomic nervous system.
The large intestine.
The primary function of the large intestine is to store and concentrate fecal material before defecation.
A secondary function is to absorb some water and ions,
and some potentially useful products of bacterial metabolism.
Anatomy.
The large intestine is about 6.5 centimetres in diameter and 1.5 meters long.
Although the large intestine has a greater diameter than the small intestine,
its epithelial surface area is much smaller because the large intestine is shorter than the small intestine,
the surface area is not convoluted, and its mucus lacks villi.
The first portion of the large intestine is the cecum.
There is a sphincter between the ileum and the cecum.
This limits the moment of colonic contents backward into the ileum.
This prevents bacteria from the large intestine from colonising the final part of the small intestine.
The appendix is a small, finger like projection that extends from the cecum,
and may participate in immune function and serve as a reservoir for healthy bacteria,
when illness alters the bacterial population in the small intestine.
The colon consists of three relatively straight segments - the ascending, transverse,
and descending portions.
The terminal portion of the descending colon is S-shaped, falling the sigmoid colon,
which empties into a relatively straight segment of the large intestine, the rectum, which ends at the anus.
Secretion, digestion, and absorption in the large intestine.
The secretions of the large intestine are scanty, lack digestive enzymes,
and consists mostly of mucus and fluid containing HCO3- and K+.
About 1500ml of chyme enters the large intestine from the small intestine each day.
The material is derived largely from the secretions of the lower small intestine,
because most of the ingested nutrients are absorbed before reaching the large intestine.
Fluid absorption by the large intestine normally accounts for only a small fraction,
of the total fluid absorbed by the GI tract each day.
The primary absorptive process in the large intestine is the active transport of Na+ from lumen,
to extra cellular fluid, with the accompanying osmotic absorption of water.
If fecal material remains in the large intestine for a long time, almost all the water is absorbed,
leaving behind hard fecal pellets.
In contrast to Na+, there is normally a net movement of K+ from blood into the lumen.
Severe depletion of total body potassium can result when large volumes of fluid are excreted in the feces.
There is also a net movement of HCO3- into the lumen coupled to Cl- absorption from the lumen,
and the loss of HCO3- (a base) in persons with prolonged diarrhoea can cause metabolic acidosis.
The large intestine also absorbs some of the products formed by the bacteria colonising this region.
It is now recognised that the colonial bacteria make a vital metabolic contribution to health.
For example, some undigested polysaccharides (fibre) are metabolised,
and their breakdown products used to synthesise short chain fatty acids by bacteria in the large intestine,
and absorbed into the blood.
Recent evidence suggests that these fatty acids may have important functions in immunity,
cardiovascular health, and neural function.
The HCO3- secreted by the large intestine helps to neutralise the increased acidity,
resulting from the formation of these fatty acids.
Colonic bacteria also produce small amounts of vitamins, specially vitamin K,
that are absorbed into the blood.
Although this source of vitamins generally provides only a small part of the normal daily requirement,
it might make a significant contribution when dietary vitamin intake is low.
Other bacterial products include gas (flatus) which is a mixture of nitrogen and carbon dioxide,
with small amounts of the gases hydrogen, methane, and hydrogen sulphide.
Bacterial fermentation of undigested polysaccharides produces these gases in the colon,
(except for nitrogen, which is derived from swallowed air) at the rate of 400 to 700 milli litres per day.
Certain foods (beans, for example) contains large amounts of carbohydrates,
that cannot be digested by intestinal enzymes but are really metabolised by bacteria in the large intestine, producing large amounts of gas.
Motility of the large intestine and defecation.
Contraction of the smooth muscle in the large intestine produce a segmentation motion,
with a rhythm considerably slower (one every 30 minutes) than that in the small intestine.
Because of the slow propulsion of the large intestine contents,
material entering from the small intestine remain for 18 to 24 hours.
This provides time for bacteria to grow and multiply.
3 to 4 times a day, generally following a meal, a wave of intense contraction known as a mass movement, spreads rapidly over the traverse segment of the large intestine towards the rectum.
The large intestine is innervated by parasympathetic and sympathetic nerves.
Parasympathetic input increases segmental contractions,
while sympathetic inputs decreases colonic contractions.
The anus, the exit from the rectum, is normally closed by the internal and sphincter,
composed of skeletal muscle under voluntary control.
The sudden distension of the walls of the rectum produced by the mass movement,
of fecal material into it initiates the neurally mediated defecation reflex.
The conscious urge to defecate, mediated by mechanoreceptors,
accompanies distension of the rectum and relaxation of the internal anal sphincter,
but contraction of the external anal sphincter (initially) and increased motility in the sigmoid colon.
Eventually, a pressure is reached in the rectum that triggers reflex relaxation of the external anal sphincter,
allowing the feces to be expelled.
Via descending pathways to somatic nerves to the external anal sphincter,
brain centres can overwrite the reflex signals that eventually would relax the sphincter,
thereby keeping the external sphincter closed and allow the person to delay defecation.
In this case, the prolonged distinction of the rectum initiates a reverse movement,
driving the rectum contents back into the sigmoid colon.
The urge to defecate then subsides until the next mass movement again propels more feces into the rectum, increasing its volume and again initiating the defecation reflex.
End of Module.