Download The Mouth and Esophagus

Digestive System Expert/Analogies – A Group Activity
Objective:
This exercise will be used as a group activity when studying the human digestive system. There are two parts
to this poster activity. One half of your poster will include an actual diagram of the specific organ along with
answers to the questions preceding your information packet. On the other half of the poster you are to relate a
common kitchen item to the function of your specific digestive organ.
Procedure:
In the table below you will see a list of some of the major organs of the digestive system. (Use the chart to jot
down your ideas before writing on poster paper) As a group, decide on which item or appliance that you would
find in a kitchen would be the most analogous to the organ named. Use your poster paper to write down the
name of the organ, the appliance which you compared it to, and then the rationale. Make sure your rationale
gives reasons your group chose this particular item.
Make your posters neat and presentable – they will be on display. Near the end of the class your group will
explain your choices to the other groups and record their rationales.
ORGAN
ITEM(S)
RATIONALE
1. Tongue
2. Teeth
3. Salivary
glands
4. Esophagus
5. Stomach
6. Small
Intestine
7. Pancreas
8. Liver
9. Gall Bladder
10. Colon
11. Rectum &
Anus
1
The Teeth
As a group you have the task of becoming an expert on The Teeth. You need to complete the tasks that are
outlined below. Use each other as a resource and make sure you understand all the tasks fully as you will have
the responsibility of explaining the teeth to your classmates.
1.
2.
3.
4.
5.
Explain the structure of the teeth. Beside each structure list the function of the structure.
Draw a diagram of the teeth – label the important structures.
Explain the types of mechanical digestion that the teeth engage in.
Explain how this benefits chemical digestion.
Describe one common ailment that afflicts the teeth and how it can be treated and prevented.
Background http://www.uic.edu/classes/bios/bios100/lecturesf04am/lect20.htm
Mastication, or chewing, is the first step in the breakdown of complex foodstuffs and serves several functions,
including:
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breaking large pieces into small pieces, resulting in a massive increase in surface area, which is where
digestive enzymes work
softening of food and transformation into a size conducive to swallowing
lubrication of food by impregnating it with saliva
Chewing is, to a large extent, a reflex, although you can voluntarily masticate as well. To study this
phenomenon, watch a cow ruminating or look around and watch someone chewing gum. The presence of food
(or gum) in the mouth causes a reflex inhibition of the muscles of the lower jaw. Those muscles relax and the
lower jaw drops, causing a stretch reflex which causes muscle contraction and closure of the mouth. During
mastication, the tongue and, to a lesser extent, the lips and cheeks acts to keep food between the grinding
surfaces of the teeth. This can be demonstrated by trying to chew your next meal while holding your tongue
still. Incidentally, chewing is hard work and expends a lot of energy.
Deficits in the ability to effectively masticate are a very common cause of digestive disease in animals. Many of
these problems are associated with poor teeth, and most are easily diagnosed by simple inspection. A
particularly common problem in horses is the occurrence of "points" on the molar teeth.
The final step in pregastric digestion is swallowing, also known as deglutition. This is really a very complex
process that can be thought of as occurring in three steps:
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First, a bolus of food is pressed backward into the pharynx by the tongue. This is the only step that is
voluntary - the remaining steps occur by reflex.
Once the bolus reaches the pharynx several actions are initiated, which basically involve shunting the bolus
into the esophagus while at the same time closing alternative routes of escape. The lumen of the larynx is
squeezed shut and the epiglottis swings backward to cover the larynx. The larynx is also pulled forward and
down making the opening to the esophagus larger.
Finally, the tongue presses backward and a peristaltic contraction in the pharynx propels the bolus into the
esophagus, where the actual act of swallowing takes place.
During swallowing, boluses of food are propelled through the esophagus by strong peristaltic contractions. In
dogs and humans, it takes 4-5 seconds for the bolus to traverse the esophagus. If the bolus is not delivered in
"one pass", secondary waves of peristalsis are initiated at the point of distention, which almost always result in
delivery of the bolus to the stomach. Congenital and acquired disorders in esophageal motility that interfere with
this usually reliable delivery of food are rather common in both animals and man.
2
http://www.bbc.co.uk/science/humanbody/body/factfiles/teeth/teeth.shtml
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Food processing: Teeth cut through and chew up food, preparing it for digestion
Enamel: Is the hardest substance in the human body
 Tooth decay: Bacteria in your mouth produce acid which rots your teeth
Teeth break down food
 Your teeth prepare food for digestion by breaking it down and chewing it up. They do this by
cutting, tearing, crushing and grinding:
 Your eight flat front teeth are good for biting, scraping and cutting. They are called incisors
 Your four cone shaped canines are good at piercing and tearing food
 The teeth that crush and grind your food are your eight blunt premolars and your twelve broader,
larger molars
Hard teeth have a soft centre
 Your teeth are covered in enamel, which is the hardest substance in your body. It covers the exposed
part of your teeth above your gum. The roots of your teeth are fixed into a socket in your jawbone.
 Although your teeth are hard on the outside, they actually have a soft centre. Inside your teeth is a
cavity filled with pulp. Pulp is made up of connective tissue, blood vessels, and nerve fibers. It
supplies nutrients to your teeth. The pulp cavity extends into the root of your teeth, forming the root
canal.
Two sets of teeth
 The first set of teeth known as deciduous or milk teeth erupts through the gums between eight
months and three years of age. Milk teeth become loose and start to fall out as permanent teeth push
through the gums at about six years of age. A full set of 32 permanent teeth is complete when
wisdom teeth appear in the late teens or early twenties.
 The reason you have two sets of teeth probably comes down to size. A full set of permanent teeth
would be too big to fit into a young child's mouth. So milk teeth act as a bridge until the jaw is large
enough to accommodate a full set of permanent teeth.
 Wisdom teeth
 The last teeth that emerge are your wisdom teeth. It's not clear what their function is, but some
experts believe they're a remnant from a time when our ancestors had a more rugged diet and, as a
result, longer, larger jaws. Now our jaws are smaller, there often isn't enough room for them, which
is why wisdom teeth can cause problems.
Tooth decay
 There are bacteria in your mouth that multiply when you eat sweet food. As these bacteria feed on
food stuck on your teeth, they produce acid. This acid can dissolve enamel and eat through a tooth,
right down to the nerve in its pulp cavity. A hole in a tooth like this provides a route for bacteria in
your mouth to cause nasty infections in the root of a tooth. This can result in excruciating toothache.
3
The Mouth and Tongue
As a group you have the task of becoming an expert on The Tongue. You need to complete the tasks that are
outlined below. Use each other as a resource and make sure you understand all the tasks fully as you will have
the responsibility of explaining The Tongue to your classmates.
1.
2.
3.
4.
5.
Explain the structure of the mouth and tongue. Beside each structure list the function of the structure.
Draw a diagram of the mouth and tongue – label the important structures.
Explain the types of mechanical digestion that the tongue engages in.
Explain how this benefits chemical digestion.
Describe one common ailment that afflicts the mouth/tongue and how it can be treated and prevented.
Background http://www.uic.edu/classes/bios/bios100/lecturesf04am/lect20.htm
Mechanical breakdown begins in the mouth by chewing (teeth) and actions of the tongue. Chemical breakdown
of starch by production of salivary amylase from the salivary glands. This mixture of food and saliva is then
pushed into the pharynx and esophagus. The esophagus is a muscular tube whose muscular contractions
(peristalsis) propel food to the stomach.
In the mouth, teeth, jaws and the tongue begin the mechanical breakdown of food into smaller particles. Most
vertebrates, except birds (who have lost their teeth to a hardened bill), have teeth for tearing, grinding and
chewing food. The tongue manipulates food during chewing and swallowing; mammals have taste buds
clustered on their tongues.
Salivary glands secrete salivary amylase, an enzyme that begins the breakdown of starch into glucose. Mucus
moistens food and lubricates the esophagus. Bicarbonate ions in saliva neutralize the acids in foods.
The Physiology of Taste
The sense of taste affords an animal the ability to evaluate what it eats and drinks. At the most basic level,
this evaluation is to promote ingestion of nutritious substances and prevent consumption of potential poisons
or toxins. There is no doubt that animals, including humans, develop taste preferences. That is, they will
choose certain types of food in preference to others. Interestingly, taste preference often changes in
conjunction with body needs. Similarly, animals often develop food aversions, particularly if they become ill
soon after eating a certain food, even though that food was not the cause of the illness - surely you have
experienced this yourself. Food preferences and aversions involve the sense of taste, but these phenomena
are almost certainly mediated through the central nervous system.
Taste Receptor Cells, Taste Buds and Taste Nerves
The sense of taste is mediated by taste receptor cells which are bundled in clusters called taste buds. Taste
receptor cells sample oral concentrations of a large number of small molecules and report a sensation of taste
to centers in the brainstem.
In most animals, including humans, taste buds are most prevalent on small pegs of epithelium on the tongue
called papillae. The taste buds themselves are too small to see without a microscope, but papillae are readily
observed by close inspection of the tongue's surface. To make them even easier to see, put a couple of drops
of blue food coloring on the tongue of a loved one, and you'll see a bunch of little pale bumps - mostly fungi
form papillae - stand out on a blue background.
4
Taste buds are composed of groups of between 50 and 150 columnar taste receptor cells bundled together
like a cluster of bananas. The taste receptor cells within a bud are arranged such that their tips form a small
taste pore, and through this pore extend microvillus from the taste cells. The microvilli of the taste cells bear
taste receptors.
Interwoven among the taste cells in a taste bud is
a network of dendrites of sensory nerves called
"taste nerves". When taste cells are stimulated
by binding of chemicals to their receptors, they
depolarize and this depolarization is transmitted
to the taste nerve fibers resulting in an action
potential that is ultimately transmitted to the
brain. One interesting aspect of this nerve
transmission is that it rapidly adapts - after the
initial stimulus, a strong discharge is seen in the
taste nerve fibers but within a few seconds, that
response diminishes to a steady-state level of
much lower amplitude.
Once taste signals are transmitted to the brain, several efferent neural pathways are activated that are
important to digestive function. For example, tasting food is followed rapidly by increased salivation and by
low level secretory activity in the stomach.
Among humans, there is substantial difference in taste sensitivity. Roughly one in four people is a
"supertaster" that is several times more sensitive to bitter and other tastes than those that taste poorly. Such
differences are heritable and reflect differences in the number of fungi form papillae and hence taste buds on
the tongue.
In addition to signal transduction by taste receptor cells, it is also clear that the sense of smell profoundly
affects the sensation of taste. Think about how tastes are blunted and sometimes different when your sense of
smell is disrupted due to a cold.
Taste Sensations
The sense of taste is equivalent to excitation of taste receptors, and receptors for a large number of specific
chemicals have been identified that contribute to the reception of taste. Despite this complexity, five types of
tastes are commonly recognized by humans:
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Sweet - usually indicates energy rich nutrients
Umami - the taste of amino acids (e.g. meat broth or aged cheese)
Salty - allows modulating diet for electrolyte balance
Sour - typically the taste of acids
Bitter - allows sensing of diverse natural toxins
5
None of these tastes are elicited by a single chemical. Also, there are thresholds for detection of taste that
differ among chemicals that taste the same. For example, sucrose, 1-propyl-2 amino-4-nitrobenzene and
lactose all taste sweet to humans, but the sweet taste is elicited by these chemicals at concentrations of
roughly 10 mM, 2 uM and 30 mM respectively - a range of potency of roughly 15,000-fold. Substances
sensed as bitter typically have very low thresholds.
Examples of some human thresholds
Taste
Substance
Threshold for tasting
Salty
NaCl
0.01 M
Sour
HCl
0.0009 M
Sweet
Sucrose
0.01 M
Bitter
Quinine
0.000008 M
Umami
Glutamate
0.0007 M
It should be noted that these tastes are based on human sensations and some comparative physiologists
caution that each animal probably lives in its own "taste world". For animals, it may be more appropriate to
discuss tastes as being pleasant, unpleasant or indifferent. Additionally, there are some clear differences
among animals in what they can taste. Cats, for example, do not respond to sweets due to a deletion in the
gene that encodes one of the sweet receptors.
Perception of taste also appears to be influenced by thermal stimulation of the tongue. In some people,
warming the front of the tongue produces a clear sweet sensation, while cooling leads to a salty or sour
sensation.
Taste Receptors
A very large number of molecules elicit taste sensations through a rather small number of taste receptors.
Furthermore, it appears that individual taste receptor cells bear receptors for one type of taste. In other
words, within a taste bud, some taste receptor cells sense sweet, while others have receptors for bitter, sour,
salty and umami tastes. Much of this understanding of taste receptors has derived from behavioral studies
with mice engineered to lack one or more taste receptors.
The pleasant tastes (sweet and umami) are mediated by a family of three T1R receptors that assemble in
pairs. Diverse molecules that lead to a sensation of sweet bind to a receptor formed from T1R2 and T1R3
subunits. Cats have a deletion in the gene for T1R2, explaining their non-responsiveness to sweet tastes.
Also, mice engineered to express the human T1R2 protein have a human-like response to different sweet
tastes. The receptor formed as a complex of T1R1 and T1R3 binds L-glutamate and L-amino acids, resulting
in the umami taste.
The bitter taste results from binding of diverse molecules to a family of about 30 T2R receptors. Sour tasting
itself involves activation of a type of TRP (transient receptor potential) channel. Surprisingly, the molecular
mechanisms of salt taste reception are poorly characterized relative to the other tastes.
6
http://www.bbc.co.uk/science/humanbody/body/articles/senses/supertaster.shtml
Science of supertasters
Brussels sprouts - for some people these miniature cabbages are the highlight of their Christmas dinner, others
shudder at the mere thought of them. Scientists now know that not all people experience tastes in the same way.
This is mainly down to the number of taste buds on your tongue.
 The more taste buds you have, the more intensely you perceive tastes, especially bitter ones. People who are
particularly sensitive are called supertasters. They can have up to twice as many taste buds as the rest of us.
 Bitter chemical
 Taste researchers divide people into three groups:
 Non-tasters
 Medium tasters
 Supertasters
 Studies have shown that around 25% of people are said to be non-tasters, 25% supertasters and 50%
medium tasters. These numbers can vary depending on sex and ethnicity. Women are more likely to be
supertasters and so are people from Asia, Africa and South America.
 Whether you're a non-taster or a supertaster or somewhere in-between depends on your sensitivity to a bitter
chemical called 6-n-propylthiouracil (PROP). Non-tasters can't taste the bitterness of PROP at all. Medium
tasters sense the bitterness but don’t mind it, while supertasters find the taste of PROP revolting.
 Children taste PROP more strongly than adults and, unlike adults; they always seem to sense the bitterness
of the chemical. So it could be that certain flavours taste different to children than they do to most adults.
This might explain why they're often fussy about their food.
Health effects
 The supertaster gene could be a remnant of our evolutionary past, acting as a safety mechanism to stop us
eating unsafe foods and toxins.
 Nowadays, the supertaster gene appears to affect people's wellbeing in other ways. Take flavonoids for
example. These are the healthy antioxidant chemicals found in fruit and vegetables. Flavonoids taste
unpleasantly bitter to supertasters, so they often avoid foods which contain high levels of them. On the other
hand, they tend to have a lower risk of heart disease, because they also shy away from very fatty, salty and
sugary foods.
7
The Salivary Glands & Saliva
As a group you have the task of becoming an expert on The Salivary Glands. You need to complete the tasks
that are outlined below. Use each other as a resource and make sure you understand all the tasks fully as you
will have the responsibility of explaining The Salivary Glands to your classmates.
1.
2.
3.
4.
5.
Explain the structure of the salivary gland. Beside each structure list the function of the structure.
Draw a diagram of the salivary gland – label the important structures.
Explain the types of mechanical digestion that the salivary gland engages in.
Explain how the salivary gland benefits chemical digestion.
Describe one common ailment that afflicts the salivary gland and how it can be treated and prevented.
Background http://www.vivo.colostate.edu/hbooks/pathphys/digestion/pregastric/salivary.html
Saliva is produced in and secreted from salivary glands. The basic secretory units of salivary glands are
clusters of cells called acini. These cells secrete a fluid that contains water, electrolytes, mucus and enzymes,
all of which flow out of the acinus into collecting ducts.
Within the ducts, the composition of the secretion is altered. Much of the sodium is actively reabsorbed,
potassium is secreted, and large quantities of bicarbonate ion are secreted. Bicarbonate secretion is of
tremendous importance to ruminants because it, along with phosphate, provides a critical buffer that
neutralizes the massive quantities of acid produced in the four stomachs. Small collecting ducts within salivary
glands lead into larger ducts, eventually forming a single large duct that empties into the oral cavity.
Most animals have three major pairs of salivary glands that differ in the type of secretion they produce:
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parotid glands produce a serous, watery secretion
sub maxillary (mandible) glands produce a mixed serous and mucous secretion
sublingual glands secrete a saliva that is predominantly mucous in character
The basis for different glands secreting saliva of differing composition can be seen by examining salivary
glands histologically. Two basic types of acinar epithelial cells exist:
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serous cells, which secrete a watery fluid, essentially devoid of mucus
mucous cells, which produce a very mucus-rich secretion
Acini in the parotid glands are almost exclusively of the serous type, while those in the sublingual glands are
predominantly mucus cells. In the sub maxillary glands, it is common to observe acini composed of both
serous and mucus epithelial cells.
In the histologic sections of canine salivary gland shown above, the cells stained pink are serous cells, while
the white, foamy cells are mucus-secreting cells.
Secretion of saliva is under control of the autonomic nervous system, which controls both the volume and type
of saliva secreted. This is actually fairly interesting: a dog fed dry dog food produces saliva that is
predominantly serous, while dogs on a meat diet secrete saliva with much more mucus. Parasympathetic
stimulation from the brain, as was well demonstrated by Ivan Pavlov, results in greatly enhanced secretion, as
well as increased blood flow to the salivary glands.
8
Potent stimuli for increased salivation include the presence of food or irritating substances in the mouth, and
thoughts of or the smell of food. Knowing that salivation is controlled by the brain will also help explain why
many psychic stimuli also induce excessive salivation - for example, why some dogs salivate all over the
house when it's thundering
What then are the important functions of saliva? Saliva serves many roles, some of which are important to all
species, and others to only a few:
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Lubrication and binding: the mucus in saliva is extremely effective in binding masticated food into a slippery
bolus that (usually) slides easily through the esophagus without inflicting damage to the mucosa. Saliva also
coats the oral cavity and esophagus, and food basically never directly touches the epithelial cells of those
tissues.
Solubilizes dry food: in order to be tasted, the molecules in food must be solubilized.
Oral hygiene: The oral cavity is almost constantly flushed with saliva, which floats away food debris and keeps
the mouth relatively clean. Flow of saliva diminishes considerably during sleep, allow populations of bacteria to
build up in the mouth -- the result is dragon breath in the morning. Saliva also contains lysozyme, an enzyme
that lyses many bacteria and prevents overgrowth of oral microbial populations.
Initiates starch digestion: in most species, the serous acinar cells secrete an alpha-amylase which can begin to
digest dietary starch into maltose. Amylase is not present, or present only in very small quantities, in the saliva
of carnivores or cattle.
Provides alkaline buffering and fluid: this is of great importance in ruminants, which have non-secretory fore
stomachs.
Evaporative cooling: clearly of importance in dogs, which have very poorly developed sweat glands - look at a
dog panting after a long run and this function will be clear.
Diseases of the salivary glands and ducts are not uncommon in animals and man, and excessive salivation is a
symptom of almost any lesion in the oral cavity. The dripping of saliva seen in rabid animals is not actually a
result of excessive salivation, but due to pharyngeal paralysis, which prevents saliva from being swallowed.
9
The Esophagus
1.
2.
3.
4.
5.
6.
Explain the role of the esophagus in the digestive process.
Explain (summarize) the structure of the esophagus.
Draw a diagram of the esophagus relaxed and swallowing.
Explain the types of mechanical (physical) digestion that take place in the esophagus.
Explain the types of chemical digestion that take place in the esophagus.
Explain peristalsis – what is it? (you may use a diagram if it is helpful)
Background http://www.uic.edu/classes/bios/bios100/lecturesf04am/lect20.htm
The Mouth and Pharynx
Mechanical breakdown begins in the mouth by chewing (teeth) and actions of the tongue. Chemical breakdown
of starch by production of salivary amylase from the salivary glands. This mixture of food and saliva is then
pushed into the pharynx and esophagus. The esophagus is a muscular tube whose muscular contractions
(peristalsis) propel food to the stomach.
In the mouth, teeth, jaws and the tongue begin the mechanical breakdown of food into smaller particles. Most
vertebrates, except birds (who have lost their teeth to a hardened bill), have teeth for tearing, grinding and
chewing food. The tongue manipulates food during chewing and swallowing; mammals have taste buds
clustered on their tongues.
Salivary glands secrete salivary amylase, an enzyme that begins the breakdown of starch into glucose. Mucus
moistens food and lubricates the esophagus. Bicarbonate ions in saliva neutralize the acids in foods.
Swallowing moves food from the mouth through the pharynx into the esophagus and then to the stomach.
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Step 1: A mass of chewed, moistened food, a bolus, is moved to the back of the moth by the tongue. In the
pharynx, the bolus triggers an involuntary swallowing reflex that prevents food from entering the lungs, and
directs the bolus into the esophagus.
Step 2: Muscles in the esophagus propel the bolus by waves of involuntary muscular contractions
(peristalsis) of smooth muscle lining the esophagus.
Step 3: The bolus passes through the gastroesophogeal sphincter, into the stomach. Heartburn results from
irritation of the esophagus by gastric juices that leak through this sphincter.
http://www.vivo.colostate.edu/hbooks/pathphys/digestion/pregastric/esophagus.html
Anatomically and functionally, the esophagus is the least complex section of the digestive tube. Its role in
digestion is simple: to convey boluses of food from the pharynx to the stomach. The esophagus begins as an
extension of the pharynx in the back of the oral cavity. It then courses down the neck next to the trachea,
through the thoracic cavity, and penetrates the diaphragm to connect with the stomach in the abdominal
cavity.
Like other parts of the digestive tube, the esophagus has four tunics, but important differences exist in the
composition of these tunics in comparison to more distal sections of the tube.
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First, instead of the muscular tunic being entirely smooth muscle, as it is in the stomach and intestines, the
wall of the esophagus contains a variable amount of striated muscle. In dogs, cattle and sheep, its entire
10
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length is striated muscle, whereas in cats, horses and humans, the proximal esophagus has striated muscle
and the distal esophagus smooth muscle.
Second, instead of the esophagus being free as it courses through the thoracic cavity, it is embedded in the
connective tissue; thus, its outer tunic is referred to as adventitia instead of serosa.
In its role as the first conduit in the digestive tube, the esophagus is routinely exposed to rough and abrasive
foodstuffs, like fragments of bone, fibrous plant leaves and Doritos. Its surface should therefore be resistant to
trauma, and indeed, the esophagus is lined with stratified squamous epithelium, as seen below in an image
from a cat's esophagus:
Absorption in the esophagus is virtually nil. The mucosa does contain mucous glands that are expressed as
foodstuffs distend the esophagus, allowing mucus to be secreted and aid in lubrication.
The body of the esophagus is bounded by physiologic sphincters known as the upper and lower esophageal
sphincters. The upper sphincter is composed largely of a muscle that is closely associated with the larynx.
When relaxed, as it is during swallowing, this muscle pulls the larynx forward and aids in routing food into
the esophagus instead of the larynx. The lower esophageal sphincter is the muscle that surrounds the
esophagus just as it enters the stomach.
Normally, the upper and lower sphincters are closed except during swallowing, which prevents constant entry
of air from the oral cavity or reflux of stomach contents. In humans, common disorders involving the
esophagus include heartburn and gastroesophageal reflux disease (GERD). In both cases, the lower sphincter
does not close properly, allowing acid from the stomach to reflux back into the esophagus, causes a burning
sensation in the chest or throat (heartburn) or additional signs such as coughing, coughing or a sensation of
choking.
An associated problem is acid indigestion, which occurs when refluxed stomach acid is tasted. Occasional
heartburn is very common, but if it occurs more than a time or two each week, it could signify a more serious
problem that requires treatment, usually with dietary management and drugs that suppress secretion of gastric
acid.
11
The Stomach
1.
2.
3.
4.
5.
6.
7.
Explain the role of the stomach in the digestive process.
Explain (summarize) the structure of the stomach. (be sure to include the layers of the stomach wall)
Draw a diagram of the stomach filling and emptying.
Explain the types of mechanical (physical) digestion that take place in the stomach.
Explain the types of chemical digestion that take place in the stomach.
Explain peristalsis – what is it? (you may use a diagram if it is helpful)
Describe one common ailment that afflicts the stomach and how it can be treated and prevented.
Background http://www.vivo.colostate.edu/hbooks/pathphys/digestion/stomach/index.html
Foodstuffs entering the stomach have been, to at least some extent, crushed and reduced in size by mastication,
and impregnated with saliva. The stomach provides four basic functions that assist in the early stages of
digestion and prepare the chyme for further processing in the small intestine:
1. It serves as a short-term storage reservoir, allowing a rather large meal to be consumed quickly and
dealt with over an extended period of time.
2. It is in the stomach that substantial enzymatic digestion is initiated, particularly of proteins.
3. Vigorous contractions of gastric smooth muscle mix and grind foodstuffs with gastric secretions,
resulting in liquefaction of food, a prerequisite for delivery of the chyme to the small intestine.
4. As food is liquefied in the stomach, it is slowly released into the small intestine for further processing.
The stomach is an expanded section of the digestive tube between the esophagus and small intestine. It's
characteristic shape is shown, along with terms used to describe the major regions of the stomach. The right
side of the stomach shown above is called the greater curvature and that on the left the lesser curvature. The
most distal and narrow section of the stomach is termed the pylorus - as food is liquefied in the stomach it
passes through the pyloric canal into the small intestine.
The wall of the stomach is structurally similar to other parts of the digestive tube, with the exception that the
stomach has an extra, oblique layer of smooth muscle inside the circular layer, which aids in performance of
complex grinding motions.
In the empty state, the stomach is contracted and its mucosa
and sub mucosa are thrown up into distinct folds called
rugae; when distended with food, the rugae are "ironed
out" and flat. The image to the right shows rugae on the
surface of a dog's stomach.
Within the stomach there is an abrupt transition from
stratified squamous epithelium extending from the
esophagus to a columnar epithelium dedicated to secretion.
In most species, this transition is very close to the
esophageal orifice, but in some, particular horses and rodents, stratified squamous cells line much of the fundus
and part of the body.
If the lining of the stomach is examined with a hand lens, one can see that it is covered with numerous small
holes. These are the openings of gastric pits which extend into the mucosa as straight and branched tubules,
forming gastric glands.
12
Four major types of secretory epithelial cells cover the surface of the stomach and extend down into gastric pits
and glands:
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Mucous cells: secrete an alkaline mucus that protects the epithelium against shear stress and acid
Parietal cells: secrete hydrochloric acid
Chief cells: secrete pepsin, a proteolytic enzyme
G cells: secrete the hormone gastrin
There are differences in the distribution of these cell types among regions of the stomach - for example, parietal
cells are abundant in the glands of the body, but virtually absent in pyloric glands. The micrograph to the right
shows a gastric pit invaginating into the mucosa (fundic region of a raccoon stomach). Notice that all the
surface cells and the cells in the neck of the pit are foamy in appearance - these are the mucous cells. The other
cell types are farther down in the pit and, in this image, difficult to distinguish.
Contractions of gastric smooth muscle serve two basic functions:


ingested food is crushed, ground and mixed, liquefying it to form what is called chyme.
chyme is forced through the pyloric canal into the small intestine, a process called gastric emptying.
The stomach can be divided into two regions on the basis of motility
pattern: an accordian-like reservoir that applies constant pressure on the
lumen and a highly contractile grinder.
The upper stomach, composed of the fundus and upper body, shows low
frequency, sustained contractions that are responsible for generating a
basal pressure within the stomach. Importantly, these tonic contractions
also generate a pressure gradient from the stomach to small intestine and
are thus responsible for gastric emptying. Interestingly, swallowing of
food and consequent gastric distention inhibits contraction of this region
of the stomach, allowing it to balloon out and form a large reservoir
without a significant increase in pressure.
The lower stomach, composed of the lower body and antrum, develops strong peristaltic waves of contraction
that increase in amplitude as they propagate toward the pylorus. These powerful contractions constitute a very
effective gastric grinder; they occur about 3 times per minute in people and 5 to 6 times per minute in dogs.
Gastric distention strongly stimulates this type of contraction, accelerating liquefaction and hence, gastric
emptying. The pylorus is functionally part of this region of the stomach - when the peristaltic contraction
reaches the pylorus, its lumen is effectively obliterated - chyme is thus delivered to the small intestine in spurts.
The stomach is famous for its secretion of acid, but acid is only one of four major secretory products of the
gastric epithelium, all of which are important either to the digestive process or to control of gastric function:



Mucus: The most abundant epithelial cells are mucous cells, which cover the entire lumenal surface and
extend down into the glands as "mucous neck cells". These cells secrete a bicarbonate-rich mucus that
coats and lubricates the gastric surface, and serves an important role in protecting the epithelium from
acid and other chemical insults.
Acid: Hydrochloric acid is secreted from parietal cells into the lumen where it establishes an extremely
acidic environment. This acid is important for activation of pepsinogen and inactivation of ingested
microorganisms such as bacteria.
Proteases: Pepsinogen, an inactive zymogen, is secreted into gastric juice from both mucous cells and
chief cells. Once secreted, pepsinogen is activated by stomach acid into the active protease pepsin,
13

which is largely responsible for the stomach's ability to initiate digestion of proteins. In young animals,
chief cells also secrete chymosin (rennin), a protease that coagulates milk protein allowing it to be
retained more than briefly in the stomach.
Hormones: The principal hormone secreted from the gastric epithelium is gastrin, a peptide that is
important in control of acid secretion and gastric motility.
A number of other enzymes are secreted by gastric epithelial cells, including a lipase and gelatinase. One
secretory product of considerable importance in man is intrinsic factor, a glycoprotein secreted by parietal cells
that is necessary for intestinal absorption of vitamin B12.
The stomach absorbs very few substances, although small amounts of certain lipid-soluble compounds can be
taken up, including aspirin, other non-steroidal anti-infammatory drugs, and ethanol.
Notably, these substances are also well-recognized causes of gastric irritation and their use (especially overuse)
is commonly associated with development of gastritis and gastric ulcers.
One Meal in the Life of the Stomach
The stomach functions dynamically, in parallel with meals. Consider the stomach's most notable activity secretion of acid. Acid is secreted in large quantities when the stomach is distended with food, which is useful
because it facilitates the initial breakdown of proteins. However, once the meal has been liquefied and the
stomach has emptied, acid secretion trickles to a stop and remains shut off during the interdigestive period. This
shut-off in acid secretion is a good thing - otherwise excessive acid would damage the mucosa of the stomach
and small intestine, as happens in certain disease states.
Gastric function is often classified into three phases in which secretory and motor activities are tightly coupled.
Try identifying these phases in yourself or your loved ones around meal time:
Cephalic phase ("wake up call"): Seeing, smelling and anticipating food in perceived in the brain and the
brain informs the stomach that it should prepare for receipt of a meal.
This communication is composed of parasympathetic stimuli transmitted through the vagus nerve to the enteric
nervous system, resulting in release of acetylcholine in the vicinity of G cells and parietal cells. Binding of
acetylcholine to its receptor on G cells induces secretion of the hormone gastrin, which, in concert with
acetylcholine and histamine, stimulates parietal cells to secrete small amounts of acid. Additionally, a low level
of gastric motility is induced. In essence, the gastric motor is turned on and begins to idle.
Gastric phase ("full steam ahead"): When a meal enters the stomach several additional factors come into
play, foremost among them distension and mucosal irritation.
Distension excites stretch receptors and irritation activates chemoreceptors in the mucosa. These events are
sensed by enteric neurons, which secrete additional acetylcholine, further stimulating both G cells and parietal
cells; gastrin from the G cells feeds back to the parietal cells, stimulating it even further. Additionally,
activation of the enteric nervous system and release of gastrin cause vigorous smooth muscle contractions. The
net result is that secretory and motor functions of the stomach are fully turned on - lots of acid and pepsinogen
are secreted, pepsinogen is converted into pepsin and vigorous grinding and mixing contractions take place.
However, there is a mechanism in place in the stomach to prevent excessive acid secretion - if lumenal pH
drops low enough (less than about 2); motility and secretion are temporarily suspended.
14
Intestinal phase ("step on the brakes"): As food is liquefied in the stomach, it is emptied into the small
intestine. Its seems to be important for the small intestine to be able to slow down gastric emptying, probably to
allow it time to neutralize the acid and efficiently absorb incoming nutrients.
Hence, this phase of gastric function is dominated by the small intestine sending inhibitory signals to the
stomach to slow secretion and motility. Two types of signals are used: nervous and endocrine. Distension of the
small intestine, as well as chemical and osmotic irritation of the mucosa is transduced into gastric-inhibitory
impulses in the enteric nervous system - this nervous pathway is called the enterogastric reflex. Secondly,
enteric hormones such as cholecystokinin and secretin are released from cells in the small intestine and
contribute to suppression of gastric activity.
Collectively, enteric hormones and the enterogastric reflex put a strong brake on gastric secretion and motility.
As the ingesta in the small intestine is processed, these stimuli diminish, the damper on the stomach is released,
and its secretory and motor activities resume.
To summarize, the brain alerts the stomach that it should expect arrival of a meal and the stomach comes out of
its interdigestive quiescence and begins low level motor and secretory activity (cephalic phase). After a meal is
consumed, the gastric motor and secretory activity is fully turned on (gastric phase). If the meal is at all
substantial, the gastric phase is periodically suppressed by signals from the small intestine and, if gastric pH
falls to very low levels, from the stomach itself. Eventually, the meal is fully liquefied and emptied, and the
stomach falls back into a state of very low motor and secretory activity, where it remains until the next cephalic
phase.
Vomiting is the forceful expulsion of contents of the stomach and often, the proximal small intestine. It is a
manifestation of a large number of conditions, many of which are not primary disorders of the gastrointestinal
tract. Regardless of cause, vomiting can have serious consequences, including acid-base derangements, volume
and electrolyte depletion, malnutrition and aspiration pneumonia.
The Act of Vomiting
Vomiting is usually experienced as the finale in a series of three events, which everyone reading this has
experienced:



Nausea is an unpleasant and difficult to describe psychic experience in humans and probably animals.
Physiologically, nausea is typically associated with decreased gastric motility and increased tone in the
small intestine. Additionally, there is often reverse peristalsis in the proximal small intestine.
Retching ("dry heaves") refers to spasmodic respiratory movements conducted with a closed glottis.
While this is occurring, the antrum of the stomach contracts and the fundus and cardia relax. Studies
with cats have shown that during retching there is repeated herniation of the abdominal esophagus and
cardia into the thoracic cavity due to the negative pressure engendered by inspiratory efforts with a
closed glottis.
Emesis or vomition is when gastric and often small intestinal contents are propelled up to and out of
the mouth. It results from a highly coordinated series of events that could be described as the following
series of steps (don't practice these in public):
o A deep breath is taken, the glottis is closed and the larynx is raised to open the upper esophageal
sphincter. Also, the soft palate is elevated to close off the posterior nares.
o The diaphragm is contracted sharply downward to create negative pressure in the thorax, which
facilitates opening of the esophagus and distal esophageal sphincter.
o Simultaneously with downward movement of the diaphragm, the muscles of the abdominal walls
are vigorously contracted, squeezing the stomach and thus elevating intragastric pressure. With
the pylorus closed and the esophagus relatively open, the route of exit is clear.
15
The Small Intestine
1.
2.
3.
4.
5.
6.
7.
8.
Explain the role of the small intestine in the digestive process.
Explain (summarize) the structure of the small intestine (size, shape, layers, etc.)
Draw a diagram of the small intestine showing the villi and micro villi.
What types of mechanical digestion take place in the small intestine?
What types of chemical digestion take place in the small intestine?
Explain the role that villi play in the absorption of food in the small intestine.
Explain peristalsis – what is it? (you may use a diagram if it is helpful)
Describe one common ailment that afflicts the small intestine and how it can be treated and prevented.
Background http://www.vivo.colostate.edu/hbooks/pathphys/digestion/smallgut/index.html
The small intestine is the portal for absorption of virtually all nutrients into blood. Accomplishing this
transport entails breaking down large supramolecular aggregates into small molecules that can be transported
across the epithelium. An exception to this statement is seen in herbivores, where large amounts of short chain
fatty acids are absorbed at other sites.
By the time ingesta reaches the small intestine, foodstuffs have been mechanically broken down and reduced to
a liquid by mastication and grinding in the stomach. Once within the small intestine, these macromolecular
aggregates are exposed to pancreatic enzymes and bile, which enables digestion to molecules capable or almost
capable of being absorbed. The final stages of digestion occur on the surface of the small intestinal epithelium.
The net effect of passage through the small intestine is absorption of most of the water and electrolytes
(sodium, chloride, potassium) and essentially all dietary organic molecules (including glucose, amino acids and
fatty acids). Through these activities, the small intestine not only provides nutrients to the body, but plays a
critical role in water and acid-base balance.
The small intestine is the longest section of the digestive tube and consists of three segments forming a passage
from the pylorus to the large intestine:



Duodenum: a short section that receives secretions from the pancreas and liver via the pancreatic and
common bile ducts.
Jejunum: considered to be roughly 40% of the small gut in man, but closer to 90% in animals.
Ileum empties into the large intestine; considered to be about 60% of the intestine in man, but
veterinary anatomists usually refer to it as being only the short terminal section of the small intestine.
In most animals, the length of the small intestine is roughly 3.5 times body length - your small intestine, or that
of a large dog, is about 6 meters in length. Although precise boundaries between these three segments of bowel
are not observed grossly or microscopically, there are histologic
differences among duodenum, jejunum and ileum.
A bulk of the small intestine is suspended from the body wall by an
extension of the peritoneum called the mesentery. As seen in the
image to the right, blood vessels to and from the intestine lie
between the two sheets of the mesentery. Lymphatic vessels are
also present, but are not easy to discern grossly in normal
specimens.
16
It is within the small intestine that the final stages of enzymatic digestion occur, liberating small molecules
capable of being absorbed. The small intestine is also the sole site in the digestive tube for absorption of amino
acids and monosaccharides. Most lipids are also absorbed in this organ. All of this absorption and much of the
enzymatic digestion takes place on the surface of small intestinal epithelial cells, and to accomodate these
processes, a huge mucosal surface area is required.
If the small intestine is viewed as a simple pipe, its lumenal surface area would be on the order of one half of a
square meter. But in reality, the absorptive surface area of the small intestine is roughly 250 square meters - the
size of a tennis court! How is this possible? At first glance, the structure of the small intestine is similar to other
regions of the digestive tube, but the small intestine incorporates three features which account for its huge
absorptive surface area:



Mucosal folds: the inner surface of the small intestine is not flat, but thrown into circular folds, which
not only increase surface area, but aid in mixing the ingesta by acting as baffles.
Villi: the mucosa forms multitudes of projections which protrude into the lumen and are covered with
epithelial cells.
Microvilli: the lumenal plasma membrane of absorptive epithelial cells is studded with densely-packed
microvilli.
The panels below depict the bulk of this surface area expansion, showing villi, epithelial cells that cover the
villi and the microvilli of the epithelial cells. Note in the middle panel, a light micrograph, that the microvilli
are visible and look something like a brush. For this reason, the microvillus border of intestinal epithelial cells
is referred to as the "brush border".
Most of the discussion on following pages focuses on enterocytes, the epithelial cells which mature into
absorptive epithelial cells that cover the villi. These are the cells that take up and deliver into blood virtually all
nutrients from the diet. However, two other major cell types populate the small intestinal epithelium:


Enteroendocrine cells which, as part of the enteric endocrine system sense the lumenal environment
and secrete hormones such as cholecystokinin and gastrin into blood.
Goblet cells, which secrete a lubricating mucus into the intestinal lumen.
Coordinated contractions of smooth muscle participate in several ways to facilitate digestion and absorption in
the small intestine:



foodstuffs are mixed with digestive enzymes from the pancreas and bile salts from the biliary system
nutrient molecules in the lumen are constantly dispersed, allowing them to contact the epithelium where
enzymatic digestion is completed and absorption occurs
chyme is moved down the digestive tube, making way for the next load and also eliminating
undigestable, perhaps toxic substances
17
In most animals, the small intestine cycles through two states, each of which is associated with distinctive
patterns of motility:


Following a meal, when the lumen of the small intestine contains chyme, two types of motility
predominate: segmentation contractions chop, mix and roll the chyme and peristalsis slowly propels it
toward the large intestine.
The interdigestive period is seen between meals, when the lumen is largely devoid of contents. During
such times, so-called housekeeping contractions propagate from the stomach through the entire small
intestine, sweeping it clear of debris. This complex pattern of motility is also known as the migrating
motor complex and is the cause of "growling".
There are two routes for transport of molecules and ions across the
epithelium of the gut:


Across the plasma membrane of the epithelial cells (transcellular
route)
Across tight junctions between epithelial cells (paracellular route)
Some molecules, water for instance, are transported by both routes. In
contrast, the tight junctions are impermeable to large organic molecules
from the diet (e.g. amino acids and glucose). Those types of molecules are
transported exclusively by the transcellular route, and only because the
plasma membrane of the absorptive enterocytes is equipped with transporter molecules that facilitate entry into
and out of the cells.
It is important to recognize that the epithelium of the gut is not a monotonous sheet of functionally identical
cells. Additionally, tight junctions linking epithelial cells vary considerably in permiability along the
gastrointestinal tract. As ingesta travels through the intestine, it is sequentially exposed to regions having
epithelia with very different characteristics. This diversity in function results from differences in phenotype of
the enterocytes - that is, the number and type of transporter molecules they express in their plasma membrane
and the structure of the tight junctions they form. Even within a given segment there are major differences in
the type of transport that occurs - for example, cells in the crypts transport very differently than cells on the tips
of villi.
Within the intestine, there is a proximal to distal gradient in osmotic permiability. As you proceed down the
tube, the effective pore size through the epithelium decreases. This means that the duodenum is much more
"leaky" to water than the ileum and the ileum more leaky than the colon. Do not interpret this to mean that as
you go down the tube, the ability to absorb water decreases! It means that water flows across the epithelium
more "freely" in the proximal compared to distal gut because the effective pore size is larger. The distal
intestine actually can absorb water better than the proximal gut.
The observed differences in permiability to water across the epithelium is due almost entirely to differences in
conductivity across the paracellular path - the takehome message is that tight junctions vary considerably in
"tightness" along the length of the gut.
Large quantities of water are secreted into the lumen of the small intestine during the digestive process. Almost
all of this water is also reabsorbed in the small intestine. Regardless of whether it is being secreted or absorbed,
water flows across the mucosa in response to osmotic gradients.
18
Virtually all nutrients from the diet are absorbed into blood across the mucosa of the small intestine. In
addition, the intestine absorbs water and electrolytes, thus playing a critical role in maintenance of body water
and acid-base balance.
It's probably fair to say that the single most important process that takes place in the small gut to make such
absorption possible is establishment of an electrochemical gradient of sodium across the epithelial cell
boundary of the lumen. This is a critical concept and actually quite interesting. Also, as we will see,
understanding this process has undeniably resulted in the saving of millions of lives.
To remain viable, all cells are required to maintain a low intracellular concentration of sodium. In polarized
epithelial cells like enterocytes, low intracellular sodium is maintained by a large number of Na+/K+ ATPases so-called sodium pumps - embedded in the basolateral membrane. These pumps export 3 sodium ions from the
cell in exchange for 2 potassium ions, thus establishing a gradient of both charge and sodium concentration
across the basolateral membrane.
At this point, its easiest to talk separately about absorption of each of the major food groups, recognizing that
all of these processes take place simultaneously.




Water and electrolytes
Carbohydrates, after digestion to monosaccharides
Proteins, after digestion to small peptides and amino acids
Neutral fat, after digestion to monoglyceride and free fatty acids
The small intestine must absorb massive quantities of water. A normal person or animal of similar size takes in
roughly 1 to 2 liters of dietary fluid every day. On top of that, another 6 to 7 liters of fluid is received by the
small intestine daily as secretions from salivary glands, stomach, pancreas, liver and the small intestine itself.
19
Liver
1.
2.
3.
4.
5.
Explain the role that this structure plays in the digestive system.
Explain (summarize) the structure and function of the liver.
Draw a diagram of the liver and gallbladder.
What role does bile play in the digestive system?
How much bile is secreted a day? Where is it stored?
Background http://www.vivo.colostate.edu/hbooks/pathphys/digestion/liver/index.html
The liver is the largest gland in the body and performs an astonishingly large number of tasks that impact all
body systems. One consequence of this complexity is that hepatic disease has widespread effects on virtually all
other organ systems. At the risk of losing sight of the forest by focusing on the trees, we will focus on three
fundamental roles of the liver:



Vascular functions, including formation of lymph and the hepatic phagocytic system.
Metabolic achievements in control of synthesis and utilization of carbohydrates, lipids and proteins.
Secretory and excretory functions, particularly with respect to the synthesis of secretion of bile.
The latter is the only one of the three that directly affects digestion - the liver, through its biliary tract, secretes
bile acids into the small intestine where they assume a critical role in the digestion and absorption of dietary
lipids. However, understanding the vascular and metabolic functions of the liver is critical to appreciating the
gland as a whole.
The liver lies in the abdominal cavity, in contact with diaphragm. Its mass is divided into several lobes, the
number and size of which vary among species. In most mammals, a greenish sac - the gallbladder - is seen
attached to the liver and careful examination will reveal the common bile duct, which delivers bile from the
liver and gallbladder into the duodenum.
Understanding function and dysfunction of the liver, more than most other organs, depends on understanding its
structure. The major aspects of hepatic structure that require detailed attention include:



The hepatic vascular system, which has several unique characteristics relative to other organs
The biliary tree, which is a system of ducts that transports bile out of the liver into the small intestine
The three dimensional arrangements of the liver cells, or hepatocytes and their association with the
vascular and biliary systems.
The Hepatic Vascular System
The circulatory system of the liver is unlike that seen in any other organ. Of great importance is the fact that a
majority of the liver's blood supply is venous blood. The pattern of blood flow in the liver can be summarized
as follows:


Roughly 75% of the blood entering the liver is venous
blood from the portal vein. Importantly, all of the venous
blood returning from the small intestine, stomach, pancreas and
spleen converges into the portal vein. One consequence of this
is that the liver gets "first pickings" of everything absorbed in
the small intestine, which, as we will see, is where virtually all
nutrients are absorbed.
The remaining 25% of the blood supply to the liver is arterial blood from the hepatic artery.
20



Terminal branches of the hepatic portal vein and hepatic artery empty together and mix as they enter
sinusoids in the liver. Sinusoids are distensible vascular channels lined with highly fenestrated or "holey"
endothelial cells and bounded circumferentially by hepatocytes. As blood flows through the sinusoids, a
considerable amount of plasma is filtered into the space between endothelium and hepatocytes (the "space
of Disse"), providing a major fraction of the body's lymph.
Blood flows through the sinusoids and empties into
the central vein of each lobule.
Central veins coalesce into hepatic veins, which
leave the liver and empty into the vena cava.
The Biliary System
The biliary system is a series of channels and ducts that conveys bile - a secretory and excretory product of
hepatocytes - from the liver into the lumen of the small intestine. Hepatocytes are arranged in "plates" with
their apical surfaces facing and surrounding the sinusoids. The basal faces of adjoining hepatocytes are welded
together by junctional complexes to form canaliculi, the first channel in the biliary system. A bile canaliculus is
not a duct, but rather, the dilated intercellular space between adjacent hepatocytes.
Hepatocytes secrete bile into the canaliculi, and those secretions flow
parallel to the sinusoids, but in the opposite direction that blood
flows. At the ends of the canaliculi, bile flows into bile ducts, which
are true ducts lined with epithelial cells. Bile ducts thus begin in very
close proximity to the terminal branches of the portal vein and
hepatic artery, and this group of structures is an easily recognized
and important landmark seen in histologic sections of liver - the
grouping of bile duct, hepatic arteriole and portal venule is called a
portal triad.
The gall bladder is another important structure in the biliary system of many species. This is a sac-like structure
adhering to the liver which has a duct (cystic duct) that leads directly into the common bile duct. During
periods of time when bile is not flowing into the intestine, it is diverted into the gall bladder, where it is
dehydrated and stored until needed.
Architecture of Hepatic Tissue
The liver is covered with a connective tissue capsule that
branches and extends throughout the substance of the liver as
septae. This connective tissue tree provides a scaffolding of
support and the highway which along which afferent blood
vessels, lymphatic vessels and bile ducts traverse the liver.
Additionally, the sheets of connective tissue divide the
parenchyma of the liver into very small units called lobules.
The hepatic lobule is the structural unit of the liver. It consists of a roughly hexagonal arrangement of plates of
hepatocytes radiating outward from a central vein in the center. At the vertices of the lobule are regularly
distributed portal triads, containing a bile duct and a terminal branch of the hepatic artery and portal vein.
Lobules are particularly easy to see in pig liver because in that species they are well deliniated by connective
tissue septae that invaginate from the capsule.
21
The liver is well known to metabolize and excrete into bile many compounds and toxins, thus eliminating them
(usually) from the body. Examples can be found among both endogenous molecules (steroid hormones,
calcium) and exogenous compounds (many antibiotics and metabolities of drugs). A substantial number of
these compounds are reabsorbed in the small intestine and ultimately eliminated by the kidney.
One of the most important and clinically relevant examples of waste elimination via bile is that of
bilirubin. Additionally, the mechanisms involved in elimination of bilirubin are similar to those used for
elimination of many drugs and toxins.
Bilirubin is a useless and toxic breakdown product of hemoglobin, which also means that it is generated in large
quantities. In the time it takes you to read this sentence aloud, roughly 20 million of your red blood cells have
died and roughly 5 quintillion (5 x 1015) molecules of hemoglobin are in need of disposal.
Dead, damaged and senescent red blood cells are picked up by phagocytic cells throughout the body (including
Kuppfer cells in the liver) and digested. The iron is precious and is efficiently recycled. The globin chains are
protein and are catabolized and their components reused. However, hemoglobin also contains a porphyrin
called heme that cannot be recycled and must be eliminated. Elimination of heme is accomplished in a series
of steps:



Within the phagocytic cells, heme is converted through a series of steps into free bilirubin, which is
released into plasma where it is carried around bound to albumin, itself a secretory product of the liver.
Free bilirubin is stripped off albumin and absorbed by - you guessed it - hepatocytes. Within
hepatocytes, free bilirubin is conjugated to either glucuronic acid or sulfate - it is then called conjugated
bilirubin.
Conjugated bilirubin is secreted into the bile canaliculus as part of bile and thus delivered to the small
intestine. Bacteria in the intestinal lumen metabolize bilirubin to a series of other compounds which are
ultimately eliminated either in feces or, after reabsortion, in urine. The major metabolite of bilirubin in
feces is sterobilin, which gives feces their characteristic brown color.
If excessive quantities of either free or conjugated bilirubin accumulate in extracellular fluid, a yellow
discoloration of the skin, sclera and mucous membranes is observed - this condition is called icterus or
jaundice. Determining whether the excessive bilirubin is free or conjugated can aid in diagnosing the cause of
the problem.
"Looking at you with a jaundiced eye"
22
Carbohydrate Metabolism
It is critical for all animals to maintain concentrations of glucose in blood within a narrow, normal range.
Maintainance of normal blood glucose levels over both short (hours) and long (days to weeks) periods of time
is one particularly important function of the liver.
Hepatocytes house many different metabolic pathways and employ dozens of enzymes that are alternatively
turned on or off depending on whether blood levels of glucose are rising or falling out of the normal range. Two
important examples of these abilities are:


Excess glucose entering the blood after a meal is rapidly taken up by the liver and sequestered as the
large polymer, glycogen (a process called glycogenesis). Later, when blood concentrations of glucose
begin to decline, the liver activates other pathways which lead to depolymerization of glycogen
(glycogenolysis) and export of glucose back into the blood for transport to all other tissues.
When hepatic glycogen reserves become exhaused, as occurs when an animal has not eaten for several
hours, do the hepatocytes give up? No! They recognize the problem and activate additional groups of
enzymes that begin synthesizing glucose out of such things as amino acids and non-hexose
carbohydrates (gluconeogenesis). The ability of the liver to synthesize this "new" glucose is of
monumental importance to carnivores, which, at least in the wild, have diets virtually devoid of starch.
Fat Metabolism
Few aspects of lipid metabolism are unique to the liver, but many are carried out predominantly by the liver.
Major examples of the role of the liver in fat metabolism include:




The liver is extremely active in oxidizing triglycerides to produce energy. The liver breaks down many
more fatty acids that the hepatocytes need, and exports large quantities of acetoacetate into blood where
it can be picked up and readily metabolized by other tissues.
A bulk of the lipoproteins are synthesized in the liver.
The liver is the major site for converting excess carbohydrates and proteins into fatty acids and
triglyceride, which are then exported and stored in adipose tissue.
The liver synthesizes large quantities of cholesterol and phospholipids. Some of this is packaged with
lipoproteins and made available to the rest of the body. The remainder is excreted in bile as cholesterol
or after conversion to bile acids.
Protein Metabolism
The most critical aspects of protein metabolism that occur in the liver are:




Deamination and transamination of amino acids, followed by conversion of the non-nitrogenous part of
those molecules to glucose or lipids. Several of the enzymes used in these pathways (for example,
alanine and aspartate aminotransferases) are commonly assayed in serum to assess liver damage.
Removal of ammonia from the body by synthesis of urea. Ammonia is very toxic and if not rapidly and
efficiently removed from the circulation, will result in central nervous system disease. A frequent cause
of such hepatic encephalopathy in dogs and cats are malformations of the blood supply to the liver
called portosystemic shunts.
Synthesis of non-essential amino acids.
Hepatocytes are responsible for synthesis of most of the plasma proteins. Albumin, the major plasma
protein, is synthesized almost exclusively by the liver. Also, the liver synthesizes many of the clotting
factors necessary for blood coagulation.
23
The Gallbladder
1.
2.
3.
4.
5.
6.
Explain the role that this structure plays in the digestive system.
Explain (summarize) the structure and function of the gallbladder.
Draw a diagram of the liver and gallbladder.
What role does bile play in the digestive system?
How much bile is secreted a day? Where is it stored?
What happens to a person who has had their gallbladder surgically removed?
Background http://www.vivo.colostate.edu/hbooks/pathphys/digestion/liver/bile.html
Bile is a complex fluid containing water, electrolytes and a battery of organic molecules including bile acids,
cholesterol, phospholipids and bilirubin that flows through the biliary tract into the small intestine. There are
two fundamentally important functions of bile in all species:


Bile contains bile acids, which are critical for digestion and absorption of fats and fat-soluble vitamins in the small intestine.
Many waste products, including bilirubin, are eliminated from the body by secretion into bile and elimination in feces.
Adult humans produce 400 to 800 ml of bile daily, and other animals proportionately similar amounts. The
secretion of bile can be considered to occur in two stages:


Initially, hepatocytes secrete bile into canaliculi, from which it flows into bile ducts. This hepatic bile
contains large quantities of bile acids, cholesterol and other organic molecules.
As bile flows through the bile ducts it is modified by addition of a watery, bicarbonate-rich secretion
from ductal epithelial cells.
In species with a gallbladder (man and most domestic animals except horses and rats), further modification of
bile occurs in that organ. The gall bladder stores and concentrates bile during the fasting state. Typically,
bile is concentrated five-fold in the gall bladder by absorption of water and small electrolytes - virtually all of
the organic molecules are retained.
Secretion into bile is a major route for eliminating cholesterol. Free cholesterol is virtually insoluble in aqueous
solutions, but in bile, it is made soluble by bile acids and lipids like lethicin. Gallstones, most of which are
composed predominantly of cholesterol, result from processes that allow cholesterol to precipitate from
solution in bile.
Role of Bile Acids in Fat Digestion and Absorption
Bile acids are derivatives of cholesterol synthesized in the hepatocyte. Cholesterol, ingested as part of the diet
or derived from hepatic synthesis is converted into the bile acids cholic and chenodeoxycholic acids, which are
then conjugated to an amino acid (glycine or taurine) to yield the conjugated form that is actively secreted into
cannaliculi.
Bile acids are facial amphipathic, that is, they contain both
hydrophobic (lipid soluble) and polar (hydrophilic) faces. The
cholesterol-derived portion of a bile acid has one face that is
hydrophobic (that with methyl groups) and one that is hydrophilic
(that with the hydroxyl groups); the amino acid conjugate is polar and
hydrophilic.
24
Their amphipathic nature enables bile acids to carry out two important functions:


Emulsification of lipid aggregates: Bile acids have detergent action on particles of dietary fat which
causes fat globules to break down or be emulsified into minute, microscopic droplets. Emulsification is
not digestion per se, but is of importance because it greatly increases the surface area of fat, making it
available for digestion by lipases, which cannot access the inside of lipid droplets.
Solubilization and transport of lipids in an aqueous environment: Bile acids are lipid carriers and
are able to solubilize many lipids by forming micelles - aggregates of lipids such as fatty acids,
cholesterol and monoglycerides - that remain suspended in water. Bile acids are also critical for
transport and absorption of the fat-soluble vitamins.
Role of Bile Acids in Cholesterol Homeostasis
Hepatic synthesis of bile acids accounts for the majority of cholesterol breakdown in the body. In humans,
roughly 500 mg of cholesterol are converted to bile acids and eliminated in bile every day. This route for
elimination of excess cholesterol is probably important in all animals, but particularly in situations of massive
cholesterol ingestion.
Interestingly, it has recently been demonstrated that bile acids participate in cholesterol metabolism by
functioning as hormones that alter the transcription of the rate-limiting enzyme in cholesterol biosynthesis.
Enterohepatic Recirculation
Large amounts of bile acids are secreted into the intestine every day, but only relatively small quantities are lost
from the body. This is because approximately 95% of the bile acids delivered to the duodenum are absorbed
back into blood within the ileum.
Venous blood from the ileum goes straight into the portal vein, and hence through the sinusoids of the liver.
Hepatocytes extract bile acids very efficiently from sinusoidal blood, and little escapes the healthy liver into
systemic circulation. Bile acids are then transported across the hepatocytes to be resecreted into canaliculi. The
net effect of this enterohepatic recirculation is that each bile salt molecule is reused about 20 times, often two or
three times during a single digestive phase.
It should be noted that liver disease can dramatically alter this pattern of recirculation - for instance, sick
hepatocytes have decreased ability to extract bile acids from portal blood and damage to the canalicular system
can result in escape of bile acids into the systemic circulation. Assay of systemic levels of bile acids is used
clinically as a sensitive indicator of hepatic disease.
Pattern and Control of Bile Secretion
The flow of bile is lowest during fasting, and a majority of that is diverted into the gallbladder for
concentration. When chyme from an ingested meal enters the small intestine, acid and partially digested fats
and proteins stimulate secretion of cholecystokinin and secretin.
25
As discussed previously, these enteric hormones have important effects on pancreatic exocrine secretion. They
are both also important for secretion and flow of bile:


Cholecystokinin: The name of this hormone describes its effect on the biliary system - cholecysto =
gallbladder and kinin = movement. The most potent stimulus for release of cholecystokinin is the
presence of fat in the duodenum. Once released, it stimulates contractions of the gallbladder and
common bile duct, resulting in delivery of bile into the gut.
Secretin: This hormone is secreted in response to acid in the duodenum. Its effect on the biliary system
is very similar to what was seen in the pancreas - it simulates biliary duct cells to secrete bicarbonate
and water, which expands the volume of bile and increases its flow out into the intestine.
The processes of gallbladder filling and emptying described here can be visualized using an imaging technique
called scintography. This procedure is utilized as a diagnostic aid in certain types of hepatobiliary disease.
Gallstones are concretions that form in the biliary system, usually the gallbladder. Although rarely recognized
in animals, they affect a large number of people. In the US alone, it is estimated that about 20 million people
have gallstones at any given time, resulting in expeditures of about $5 billion for diagnosis and treatment. A
majority of cases are asymptomatic, but signs in clinicially affected patients range from mild abdominal pain or
minor "indigestion" to excrutiating pain, often manifest at night. There are two major types of gallstones,
which seem to form due to distinctly different pathogenetic mechanisms.
Cholesterol Stones
About 90% of gallstones are of this type. These stones can be almost pure cholesterol or mixtures of cholesterol
and substances such as mucin. Stones recovered at surgery range from about 5 mm to greater than 25 mm in
diameter.
The key event leading to formation and progression of cholesterol stones is precipitation of cholesterol in bile.
Unesterified cholesterol is virtually insoluble in aqueous solutions and is kept in solution in bile largely by
virtue of the detergent-like effect of bile salts. This is however a rather precarious situation and several factors
can tip the balance in favor of precipitation, including:



Hypersecretion of cholesterol into bile due to such things as obesity, acute high calorie intake, chronic
polyunsaturated fat diet, contraceptive steroids or pregnancy, diabetes mellitus and certain forms of
familial hypercholesterolemia.
Hyposecretion of bile salts due to such things as impaired bile salt synthesis and abnormal intestinal
loss of bile salts (e.g. recirculation failure due to ileal disease).
Impaired gallbladder function with incomplete emptying or stasis is seen in late pregnancy and with
oral contraceptive use, in patients on total parenteral nutrition and due to unknown causes, perhaps
associated with neuroendocrine dysfunction.
There are clearly important genetic determinants for cholesterol stone formation. For example, the
prevelance of the disease in descendents of Chilean Indians and in American Indians is extraordinarily high and
not accounted for by environment.
There is also an important sex bias in development of stones - the prevelance in adult females is two to three
times that seen in males and use of contraceptive steroids is a risk factor for development of gallstones.. This
sex difference is likely the manifestation of differences in sex steroids: progesterone and also probably estrogen
impair gall bladder emptying and are associated with hypersecretion of cholesterol into bile. Additionally,
estrogen treatment reduces synthesis of bile acids. These pro-precipitation factors peak during late pregnancy
when the levels of these steroid hormones are hightest, then dissipate rapidly after birth.
26
The gold standard for treatment is open cholecystectomy, but laparoscopic cholecystecomy is rapidly becoming
the treatment of choice. Medical treatment with bile salts is not extremely useful in the long term and is
expensive.
Pigment Stones
Roughly 10% of human gallstones are pigment stones composed of large quantities of bile pigments, along with
lesser amounts of cholesterol and calcium salts. The most important risk factor for development of these stones
is chronic hemolysis from almost any cause - this makes sense considering that bilirubin is a major constituent
of these stones. Additionally, some forms of pigment stones are associated with bacterial infections.
Apparently, some bacteria release glucuronidases that deconjugate bilirubin, leading to precipitation as calcium
salts.
Do You Enjoy Eating Eggs?
The major metabolic product of cholesterol is bile acids. The disposal of bile acids by secretion into bile is one
of several factors that serve to maintain normal blood cholesterol concentrations, as was demonstrated in an
elderly man with a compulsion to eat eggs.
The subject of this case was an 88-year-old man living alone in a retirement community. He was healthy except
for having Alzheimer's disease. He also had a compulsive disorder which led him to consume, in addition to
regular meals, 25 soft-boiled eggs every day. Remarkably, there was good evidence from several sources that
this egg-eating behavior had been going on for at least 15 years.
The patient's medical records documented numerous serum cholesterol measurements within the normal range.
A number of metabolic studies indicated that the patient had several compensatory mechanisms in place which
enabled him to maintain normal blood cholesterol concentrations in the face of longstanding and massive
cholesterol intake:



Marked reduction in cholesterol absorption - the mechanism for this effect is not known
Greatly increased synthesis of bile acids - the patient synthesized roughly twice the mass of bile acids as
control subjects
Reduced endogenous cholestrol synthesis
The authors indicated that it would have been interesting to study this patient on a low-cholesterol diet, but that
his behavioral disorder prevented it.
27
The Pancreas
1.
2.
3.
4.
5.
6.
Explain the structure and location of the pancreas.
What is the function of the pancreas in the digestive system?
Draw a diagram of the pancreas illustrating it’s location in relationship to the duodenum.
What chemicals does the pancreas secrete.
Describe a common ailment affecting the pancreas.
How can this condition be treated and prevented?
Background http://www.vivo.colostate.edu/hbooks/pathphys/digestion/pancreas/index.html
As chyme floods into the small intestine from the stomach, two things must happen:


acid must be quickly and efficiently neutralized to prevent damage to the duodenal mucosa
macromolecular nutrients - proteins, fats and starch - must be broken down much further before their
constitutents can be absorbed through the mucosa into blood
The pancreas plays a vital role in accomplishing both of these objectives, so vital in fact that insufficient
exocrine secretion by the pancreas leads to starvation, even if the animal is consuming adequate quantities of
high quality food.
In addition to its role as an exocrine organ, the pancreas is also
an endocrine organ and the major hormones it secretes - insulin
and glucagon - play a vital role in carbohydrate and lipid
metabolism. They are, for example, absolutely necessary for
maintaining normal blood concentrations of glucose.
The pancreas is a elongated organ, light tan or pinkish in color,
that lies in close proximity to the duodenum. It is covered with a very thin connective tissue capsule which
extends inward as septa, partitioning the gland into lobules. The image above shows a canine pancreas in
relation to the stomach and duodenum.
The bulk of the pancreas is composed of pancreatic exocrine cells and their associated ducts. Embedded within
this exocrine tissue are roughly one million small clusters of cells called the Islets of Langerhans, which are the
endocrine cells of the pancreas and secrete insulin, glucagon and several other hormones. In the histologic
image of an equine pancreas seen below, a single islet is seen in the middle as a
large, pale-staining cluster of cells. All of the surrounding tissue is exocrine.
Pancreatic exocrine cells are arranged in grape-like clusters called acini (a single
one is an acinus). The exocrine cells themselves are packed with membranebound secretory granules which contain digestive enzymes that are exocytosed
into the lumen of the acinus. From there these secretions flow into larger and
larger, intralobular ducts, which eventually coalesce into the main pancreatic
duct which drains directly into the duodenum.
The lumen of an acinus communicates directly with intralobular ducts, which coalesce into interlobular ducts
and then into the major pancreatic duct. Epithelial cells of the the intralobular ducts actually project "back" into
the lumen of the acinus, where they are called centroacinar cells. The anatomy of the main pancreatic duct
varies among species. In some animals, two ducts enter the duodenum rather than a single duct. In some
species, the main pancreatic duct fuses with the common bile duct just before its entry into the duodenum.
28
Pancreatic juice is composed of two secretory products critical to proper digestion: digestive enzymes
and bicarbonate. The enzymes are synthesized and secreted from the exocrine acinar cells, whereas
bicarbonate is secreted from the epithelial cells lining small pancreatic ducts.
Digestive Enzymes
The pancreas secretes a magnificent battery of enzymes that collectively have the capacity to reduce virtually
all digestible macromolecules into forms that are capable of, or nearly capable of being absorbed. Three major
groups of enzymes are critical to efficient digestion:
1. Proteases
Digestion of proteins is initiated by pepsin in the stomach, but the bulk of protein digestion is due to the
pancreatic proteases. Several proteases are synthesized in the pancreas and secreted into the lumen of the small
intestine. The two major pancreatic proteases are trypsin and chymotrypsin, which are synthesized and
packaged into secretory vesicles as an the inactive proenzymes trypsinogen and chymotrypsinogen.
As you might anticipate, proteases are rather dangerous enzymes to have in cells, and packaging of an inactive
precursor is a way for the cells to safely handle these enzymes. The secretory vesicles also contain a trypsin
inhibitor which serves as an additional safeguard should some of the trypsinogen be activated to trypsin;
following exocytosis this inhibitor is diluted out and becomes ineffective - the pin is out of the grenade.
Once trypsinogen and chymotrypsinogen are released into the lumen of the small intestine, they must be
converted into their active forms in order to digest proteins. Trypsinogen is activated by the enzyme
enterokinase, which is embedded in the intestinal mucosa.
Once trypsin is formed it activates chymotrypsinogen, as well as additional molecules of trypsinogen. The net
result is a rather explosive appearance of active protease once the pancreatic secretions reach the small
intestine.
Trypsin and chymotrypsin digest proteins
intopeptides and peptides into smaller peptides,
butthey cannot digest proteins and peptides to
single amino acids. Some of the other proteases
from the pancreas, for instance
carboxypeptidase, have that ability, but the
final digestion of peptides into amino acids is
largely the effect of peptidases on the surface of
small intestinal epithelial cells. More on this
later.
2. Pancreatic Lipase
A major component of dietary fat is
triglyceride, or neutral lipid. A triglyceride
molecule cannot be directly absorbed across the intestinal mucosa. Rather, it must first be digested into a 2monoglyceride and two free fatty acids. The enzyme that performs this hydrolysis is pancreatic lipase, which is
delivered into the lumen of the gut as a constituent of pancreatic juice.
29
Sufficient quantities of bile salts must also be present in the lumen of the intestine in order for lipase to
efficiently digest dietary triglyceride and for the resulting fatty acids and monoglyceride to be absorbed. This
means that normal digestion and absorption of dietary fat is critically dependent on secretions from both the
pancreas and liver.
Pancreatic lipase has recently been in the
limelight as a target for management of obesity.
The drug orlistat (Xenical) is a pancreatic lipase
inhibitor that interferes with digestion of
triglyceride and thereby reduces absorption of dietary fat. Clinical trials support the contention that inhibiting
lipase can lead to significant reductions in body weight in some patients.
3. Pancreatic Amylase
The major dietary carbohydrate for many species is starch, a storage form of glucose in plants. Amylase
(technically alpha-amylase) is the enzyme that hydrolyses starch to maltose (a glucose-glucose disaccharide), as
well as the trisaccharide maltotriose and small branchpoints fragments called limit dextrins. The major source
of amylase in all species is pancreatic secretions, although amylase is also present in saliva of some animals,
including humans.
Other Pancreatic Enzymes
In addition to the proteases, lipase and amylase, the pancreas produces a host of other digestive enzymes,
including ribonuclease, deoxyribonuclease, gelatinase and elastase.
Bicarbonate and Water
Epithelial cells in pancreatic ducts are the source of the bicarbonate and water secreted by the pancreas.
Bicarbonate is a base and critical to neutralizing the acid coming into the small intestine from the stomach. The
mechanism underlying bicarbonate secretion is essentially the same as for acid secretion parietal cells and is
dependent on the enzyme carbonic anhydrase. In pancreatic duct cells, the bicarbonate is secreted into the
lumen of the duct and hence into pancreatic juice.
As you might expect, secretion from the exocrine pancreas is regulated by both neural and endocrine controls.
During interdigestive periods, very little secretion takes place, but as food enters the stomach and, a little later,
chyme flows into the small intestine, pancreatic secretion is strongly stimulated.
Like the stomach, the pancreas is innervated by the vagus nerve, which applies a low level stimulus to secretion
in response to anticipation of a meal. However, the most important stimuli for pancreatic secretion comes from
three hormones secreted by the enteric endocrine system:
1. Cholecystokinin: This hormone is synthesized and secreted by enteric endocrine cells located in the
duodenum. Its secretion is strongly stimulated by the presence of partially digested proteins and fats in the
small intestine. As chyme floods into the small intestine, cholecystokinin is released into blood and binds to
receptors on pancreatic acinar cells, ordering them to secrete large quantities of digestive enzymes.
2. Secretin: This hormone is also a product of endocrinocytes located in the epithelium of the proximal small
intestine. Secretin is secreted (!) in response to acid in the duodenum, which of course occurs when acidladen chyme from the stomach flows through the pylorus. The predominant effect of secretin on the
pancreas is to stimulate duct cells to secrete water and bicarbonate. As soon as this occurs, the enyzmes
secreted by the acinar cells are flushed out of the pancreas, through the pancreatic duct into the duodenum.
30
3. Gastrin: This hormone, which is very similar to cholecystokinin, is secreted in large amounts by the
stomach in response to gastric distention and irritation. In addition to stimulating acid secretion by the
parietal cell, gastrin stimulates pancreatic acinar cells to secrete digestive enzymes.
Stop and think about this for a minute - control of pancreatic secretion makes perfect sense. Pancreatic
secretions contain enzymes which are needed to digest proteins, starch and triglyceride. When these substances
enter stomach, and especially the small intestine, they stimulate release of gastrin and cholecystokinin, which in
turn stimulate secretion of the enzymes of destruction.
Pancreatic secretions are also the major mechanism for neutralizing gastric acid in the small intestine. When
acid enters the small gut, it stimulates secretin to be released, and the effect of this hormone is to stimulate
secretion of lots of bicarbonate. As proteins and fats are digested and absorbed, and acid is neutralized, the
stimuli for cholecystokinin and secretin secretion disappear and pancreatic secretion falls off.
31
The Large Intestine
1.
2.
3.
4.
5.
6.
7.
Explain the role of the large intestine in the digestive process.
Explain the structure of the large intestine and draw a diagram of the large intestine.
What types of mechanical digestion take place in the large intestine?
Explain the importance of water absorption in the large intestine.
What roles do bacteria place in the large intestine?
List, and briefly explain, the three types of colonic movement that occur in the large intestine.
Briefly describe a common ailment that afflicts this structure. Include treatment and prevention in your
discussion.
Background http://www.vivo.colostate.edu/hbooks/pathphys/digestion/largegut/index.html
The large intestine is the last attraction in digestive tube and the location of the terminal phases of digestion. In
comparison to other regions of the tube, there are huge differences among species in the relative size and
complexity of the large intestine. Nonetheless, in all species it functions in three processes:
1. Recovery of water and electrolytes from ingesta: By the time ingesta reaches the terminal ileum, roughly
90% of its water has been absorbed, but considerable water and electrolytes like sodium and chloride
remain and must be recovered by absorption in the large gut.
2. Formation and storage of feces: As ingesta is moved through the large intestine, it is dehydrated, mixed
with bacteria and mucus, and formed into feces. The craftsmanship (for want of a better term) with which
this is carried out varies among species.
3. Microbial fermentation: The large intestine of all species teems with microbial life. Those microbes
produce enzymes capable of digesting many of molecules that to vertebrates are indigestible, cellulose
being a premier example. The extent and benefit of fermentation also varies greatly among species.
The large intestine is that part of the digestive tube between the terminal ileum and anus. Depending on the
species, ingesta from the small intestine enters the large intestine through either the ileocecal or ileocolic valve.
Within the large intestine, three major segments are recognized:



the cecum is a blind-ended pouch that in humans carries a worm-like extension called the vermiform
appendix.
the colon constitutes the majority of the length of the large intestine and is subclassified into ascending,
transverse and descending segments.
the rectum is the short, terminal segment of the digestive tube, continuous with the anal canal.
The variation in relative dimension of the large intestine is largely correlated with diet. In herbivores like horses
and rabbits which depend largely on microbial fermentation, the large intestine is very large and complex.
Omnivores like pigs and humans have a substantial large intestine, but nothing like that seen in herbivores.
Finally, carnivores such as dogs and cats have a simple and small large intestine.
There are many similarities in the histologic structure of the mucosa in large and small intestine. The most
obvious difference is that the mucosa of the large intestine is devoid of villi. It has numerous crypts which
extend deeply and open onto a flat lumenal surface. The stem cells which support rapid and continuous renewal
of the epithelium are located either at the bottom or midway down the crypts. These cells divide to populate the
cryptal and surface epithelium.
Mucus-secreting goblet cells are also much more abundant in the colonic epithelium than in the small gut.
32
To a first approximation, absorption and secretion in the colon is straighforward:


Absorption: water, sodium ions and chloride ions
Secretion: bicarbonate ions and mucus
Water, as always, is absorbed in response to an osmotic gradient. The mechanism responsible for generating
this osmotic pressure is essentially identical to what was seen in the small intestine - sodium ions are
transported from the lumen across the epithelium by virtue of the epithelial cells having very active sodium
pumps on their basolateral membranes and a means of absorbing sodium through their lumenal membranes.
The colonic epithelium is actually more efficient at absorbing water than the small intestine and sodium
absorption in the colon is enhanced by the hormone aldosterone.
Chloride is absorbed by exchange with bicarbonate. The resulting secretion of bicarbonate ions into the lumen
aids in neutralization of the acids generated by microbial fermentation in the large gut.
Goblet cells are abundant in the colonic epithelium, and secrete mucus in response to tactile stimuli from
lumenal contents, as well as parasympathetic stimuli from pelvic nerves. Mucus is an important lubricant that
protects the epithelium, and also serves to bind the dehydrated ingesta to form feces.
Normal feces are roughly 75% water and 25% solids. The bulk of fecal solids are bacteria and undigested
organic matter and fiber. The characteristic brown color of feces are due to stercobilin and urobinin, both of
which are produced by bacterial degradation of bilirubin. Fecal odor results from gases produced by bacterial
metabolism, including skatole, mercaptans, and hydrogen sulfide.
Three prominent patterns of motility are observed the colon:
1. Segmentation contractions which chop and mix the ingesta, presenting it to the mucosa where absorption
occurs. These contractions are quite prominent in some species, forming sacculations in the colon known as
hausta.
2. Antiperistaltic contractions propagate toward the ileum, which serves to retard the movement of ingesta
through the colon, allowing additional opportunity for absorption of water and electrolytes. Peristaltic
contractions, in addition to influx from the small intestine, facilitate movement of ingesta through the colon.
3. Mass movements constitute a type of motility not seen elsewhere in the digestive tube. Known also as
giant migrating contractions, this pattern of motility is like a very intense and prolonged peristaltic
contraction which strips an area of large intestine clear of contents.
In periods between meals, the colon is generally quiescent. Following a meal, colonic motility increases
significantly, due to signals propagated through the enteric nervous system - the so called gastrocolic and
duodenocolic reflexes, manifestation of enteric nervous system control. In humans, the signal seems to be
stimulated almost exclusively by the presence of fat in the proximal small intestine. Additionally, distension of
the colon is a primary stimulator of contractions.
Several times each day, mass movements push feces into the rectum, which is usually empty. The gastrocolic
reflex mentioned above is a stimulus for this. Distension of the rectum stimulates the defecation reflex. This is
largely a spinal reflex mediated via the pelvic nerves, and results in reflex relaxation of the internal anal
sphincter followed by voluntary relaxation of the external anal sphincter and defecation.
In humans and "house-trained" animals, defecation can be prevented by voluntary constriction of the external
sphincter. When this happens, the rectum soon relaxes and the internal sphincter again contracts, a state which
persists until another bolus of feces is forced into the rectum.
33
The Rectum, and Anus
1. Explain the structure of the rectum.
2. What role does the rectum play in the digestive system?
3. Draw a diagram of the rectum as it relates to the colon.
4.
Background http://www.vivo.colostate.edu/hbooks/pathphys/digestion/largegut/index.html
The large intestine is that part of the digestive tube between the terminal ileum and anus. Depending on the
species, ingesta from the small intestine enters the large intestine through either the ileocecal or ileocolic valve.
Within the large intestine, three major segments are recognized:



the cecum is a blind-ended pouch that in humans carries a worm-like extension called the vermiform
appendix.
the colon constitutes the majority of the length of the large intestine and is subclassified into ascending,
transverse and descending segments.
the rectum is the short, terminal segment of the digestive tube, continuous with the anal canal.
Intestinal Gas Production
A considerable amount of gas is present in the gastrointestinal contents of all animals, and much of this is
eliminated through the anus as flatus. Complaints of excessive gastrointestinal gas production in people and
their pets are common. What we know about intestinal gas production and disposition has largely be gathered
from studies with humans.
Five gases constitute greater than 99% of the gases passed as flatus: N2, O2, CO2, H2 and methane. None of
these gases has an odor, and the characteristic odor of feces is due to very small quantities of a few other gases,
including hydrogen sulfide, scatols and indoles. There is considerable individual variation in the contribution of
each of these gases to total gas, but nitrogen typically predominates. Volume of gas elaborated also varies
widely. In normal adult humans, the rate of excretion of gas per rectum ranges between 200 and 2000 ml per
day. Ingestion of certain foods, beans being the classical example, is widely recognized to increase the rate of
gas production.
There are three principal sources of the five major intestinal gases:
1. Air swallowing is the major source of gas in the stomach. Several milliliters of air are swallowed with
every bolus of food or saliva. Most of this seems to be eructated and, apparently, very little passes into the
duodenum.
2. Intraluminal generation of gases results from two major processes;
First, in the proximal intestine, the interaction of hydrogen and bicarbonate ions (principally from gastric and
pancreatic secretions) leads to generation of CO2. The amount of gas generated by this pathway is not great,
because the lumenal contents do not contain carbonic anhydrase and the dissociation of H2CO3 is thus quite
slow. Additionally, most of the CO2 produced in this way is absorbed into blood.
The second and much more productive source of gas is fermentation by colonic bacteria. Microbes appear to be
the sole source of all of the hydrogen and methane produced in the intestine. Fermentable substrates that escape
34
digestion or absorption in the small intestine are often prime substrates for bacteria in the large intestine. A
variety of fruits and vegetables contain polysaccharides that are not digested in the small intestine and lead to
voluminous gas production by microbes. Indeed, the primary medical treatment for excessive gas production is
dietary manipulation to eliminate foodstuffs that the individual cannot digest and absorb.
3. Gases readily diffuse across the mucosa. The direction of diffusion is dictated by the partial pressure of
that gas in blood versus luminal contents. For methane and hydrogen, diffusion is always out of the lumen into
blood. Nitrogen and CO2 diffuse in either direction, depending on specific conditions within the individual.
Intestinal gases are a frequent cause of minor, occasionally major, social embarrassment, but can they ever be
of truly dangerous? Both H2 and CH4 are combusible and potentially explosive. In human hospitals, there have
been many explosions in the colon triggered by use of electrocautery performed through a
proctosigmoidoscope. Many of these cases occurred when mannitol, a fermentable carbohydrate, was used as a
purgitive to cleanse the colon. Use of non-fermentable cleansing agents has virtually eliminated this kind of
accident.
Yes, there is scientific documentation to back up the common observation that consumption of beans
dramatically increases the amount of gas produced in the large intestine.
In one study (Ann NY Acad Sci 150:57, 1968) flatus production was compared in a group of subjects following
consumption of one of two types of meals. The data pretty much speak for themselves.
Composition of meal
Flatus produced
(ml/hour)
Control diet
15
Diet containing 51% of its calories as
pork and beans
176
What is the basis of this effect? Beans and other legumes contain a number of oligosaccharides (stachyose,
raffinose) that are very poorly digested in the small intestine. These carbohydrates pass into the large bowel
where they are fodder for bacterial fermentation.
Microbial Fermentation
Fermentation is the enzymatic decomposition and utililization of foodstuffs, particularly carbohydrates, by
microbes. Fermentation takes place throughout the gastrointestinal tract of all animals, but the intensity of
fermentation depends on microbe numbers, which are generally highest in the large bowel. Thus, the large
intestine is quantitatively the most important site of fermention, except for species with forestomachs
(ruminants). Further, there are major differences in the contribution of fermentation to energy production of
different species. In carnivores like dogs and cats, and even in omnivores like humans, fermentation generates
rather few calories, but in herbivores, fermentation is a way of life.
Large intestinal epithelial cells do not produce digestive enzymes, but contain huge numbers of bacteria which
have the enzymes to digest and utilize many substrates. In all animals, two processes are attributed to the
microbial flora of the large intestine:


Digestion and metabolism of carbohydrates not digested in the small intestine (e.g. cellulose, residual
starch)
Synthesis of vitamin K and certain B vitamins
35
Cellulose is common constituent in the diet of many animals, including man, but no mammalian cell is known
to produce a cellulase. Several species of bacteria in the large bowel synthesize cellulases and digest cellulose.
Importantly, the major end products of microbial digestion of cellulose and other carbohydrates are volatile
fatty acids, lactic acid, methane, hydrogen and carbon dioxide. Fermentation is thus the major source of
intestinal gas.
Volatile or short-chain fatty acids (especially acetic, propionic and butyric acids) generated from fermentation
are not only metabolized within intestinal epithelial cells, but can be absorbed by diffusion and thereby
contribute fuel to systemic energy metabolism. The concentration of volatile fatty acids in the large gut is
similar among mammals, but because of the enormous differences in the relative size of the large gut, the
importance of microbial fermentation to energy production varies considerably among species. As examples, it
has been estimated that the contribution to maintenance energy of volatile fatty acids produced in the hindgut is
6-9% in humans, 10-30% in pigs and only 2% in dogs, reflecting the relative size of their fermentation vats.
Synthesis of vitamin K by colonic bacteria provides a valuable supplement to dietary sources and makes
clinical vitamin K deficiency rare. Similarly, formation of B vitamins by the microbial flora in the large
intestine is useful to many animals. They are not absorbed in the large intestine, but are present in feces. The
behavior of coprophagy or eating feces seen particularly in rodents, rabbits and other animals is thought to be a
behavioral adaption to recovery of these valuable resources.
How long does food stay in my stomach? How long is it before a meal reaches the large intestine? The
answer to such commonly-asked questions is not necessarily simple.
First, there is considerable normal variability among healthy people and animals in transit times through
different sections of the gatrointestinal tract. Second, the time required for material to move through the
digestive tube is significantly affected by the composition of the meal. Finally, transit time is influenced by
such factors as psychological stress and even gender and reproductive status.
Several techniques have been used to measure transit times in humans and animals. Not surprisingly,
differing estimates have been reported depending on the technique used and the population of subjects being
evaluated. Some of the techniques used include:


Radiography following a barium-labelled meal. Sequential radiographs can be used to determine
when the front of the barium label reaches different regions of the digestive tube. Such meals are not
very physiologic and the technique exposes the patient to repeated exposure to radiation.
Breath hydrogen analysis. A number of carbohydrates are very poorly digested or absorbed in the
small intestine, but readily fermented by bacteria when they reach the large intestine. Fermentation
liberates hydrogen gas, which diffuses into blood and is exhaled in breath, where it can be readily
measured. Thus, after consumption of a meal containing a non-absorbable carbohydrate (lactulose or,
more commonly, baked beans), there is a large increase in exhaled hydrogen when the carbohydrate
reaches the large intestine. This provides an estimate of pre-colonic (stomach plus small intestine)
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
transit time.
Scintigraphic analyses. Meals containing pellets or colloids labelled with a small amount of
radionuclide (99mTechnetium, 113mIndium, etc.) are consumed, and the position of the radioactive
label is sequentially monitored using a gamma camera.
Studies of gastrointestinal transit have clearly demonstrated two related phenomena important to
understanding this process:
1. Substances do not move uniformly through the digestive system.
2. Materials do not leave segments of the digestive tube in the same order as they arrive.
In other words, a meal is typically a mixture of chemically and physically diverse materials, and some
substances in this mixture show accelerated transit while others are retarded in their flow downstream.
An example of how ingested substances spread out in the digestive tube rather than travel synchronously is
shown in the figure below. These data were obtained from a human volunteer that ingested a meal
containing 111Indium-labeled pellets, then measuring the location of the radioactive signal over time by
scintigraphy. It is clear that parts of the meal are entering the colon at the same time that other parts are still
in the stomach.
The discussion above should help to explain why it is difficult to state with any precision how long
ingesta remains in the stomach, small intestine and large intestine. Nonetheless, there have been many
studies on GI transit, and the table below presents rough estimates for transit times in healthy humans
following ingestion of a standard meal (i.e. solid, mixed foods).
50% of stomach contents emptied
Total emptying of the stomach
2.5 to 3 hours
4 to 5 hours
50% emptying of the small intestine
2.5 to 3 hours
Transit through the colon
30 to 40 hours
Remember that these are estimates of average transit times, and there is a great deal of variability
among individuals and in the small person at different times and after different meals.
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The Teeth
As a group you have the task of becoming an expert on The Teeth. You need to complete the tasks that are
outlined below. Use each other as a resource and make sure you understand all the tasks fully as you will have
the responsibility of explaining the teeth to your classmates.
1. Explain the structure of the teeth. Beside each structure list the function of the structure.
2. Draw a diagram of the teeth – label the important structures.
3. Explain the types of mechanical digestion that the teeth engage in.
4. Explain how this benefits chemical digestion.
5. Describe one common ailment that afflicts the teeth and how it can be treated and prevented.
38
The Mouth and Esophagus
As a group you have the task of becoming an expert on The Mouth. You need to complete the tasks that are
outlined below. Use each other as a resource and make sure you understand all the tasks fully as you will have
the responsibility of explaining The Mouth to your classmates.
1. Explain the structure of the mouth. Beside each structure list the function of the structure.
2. Draw a diagram of the mouth – label the important structures.
3. Explain the types of mechanical digestion that take place in the mouth.
4. Explain the types of chemical digestion that take place in the mouth.
5. Explain the type of mechanical digestion that takes place in the esophagus.
6. What is the function of the epiglottis?
39
The Stomach
As a group you have the task of becoming an expert on The Stomach. You need to complete the tasks that are
outlined below. Use each other as a resource and make sure you understand all the tasks fully as you will have
the responsibility of explaining The Stomach to your classmates.
1. Explain the role of the stomach in the digestive process.
2. Explain (summarize) the structure of the stomach. (be sure to include the layers of the stomach wall)
3. Draw a diagram of the stomach filling and emptying.
4. Explain the types of mechanical (physical) digestion that take place in the stomach.
5. Explain the types of chemical digestion that take place in the stomach.
6. Explain peristalsis – what is it? (you may use a diagram if it is helpful)
40
The Small Intestine
As a group you have the task of becoming an expert on The Small Intestine. You need to complete the tasks
that are outlined below. Use each other as a resource and make sure you understand all the tasks fully as you
will have the responsibility of explaining The Small Intestine to your classmates.
1.
Explain the role of the small intestine in the digestive process.
2.
Explain (summarize) the structure of the small intestine (size, shape, layers, etc.)
3.
What types of mechanical digestion take place in the small intestine?
4.
What types of chemical digestion take place in the small intestine?
5.
Explain the role that villi play in the absorption of food in the small intestine.
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Liver, Gallbladder, and Pancreas
As a group you have the task of becoming an expert on the Liver, Gallbladder, and Pancreas. You need to
complete the tasks that are outlined below. Use each other as a resource and make sure you understand all the
tasks fully as you will have the responsibility of explaining Liver, Gallbladder, and Pancreas to your
classmates.
1.Explain the role that these three structures play in the digestive system.
2.Explain (summarize) the structure and function of the liver.
3.What role does bile play in the digestive system? How much bile is secreted a day? Where is it stored?
4.Explain the structure and location of the pancreas.
5.What is the function of the pancreas in the digestive system?
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The Large Intestine, Rectum, and Anus
As a group you have the task of becoming an expert on the Large Intestine, Rectum, and Anus. You need to
complete the tasks that are outlined below. Use each other as a resource and make sure you understand all the
tasks fully as you will have the responsibility of explaining the Large Intestine, Rectum, and Anus to your
classmates.
1. Explain the role of the large intestine in the digestive process.
2. Explain the structure of the large intestine.
3. What types of mechanical digestion take place in the large intestine?
4. Explain the importance of water absorption in the large intestine.
5. What roles do bacteria place in the large intestine?
6. List, and briefly explain, the three types of colonic movement that occur in the large intestine.
7. Explain the structure of the rectum.
8. What role does the rectum play in the digestive system?
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