Fundamental Physiology and Anatomy of

the Digestive System

Simply put, the digestive system is a portal for nutrients from the environment to
gain access to the circulatory system. Before such transfer can occur, foodstuffs first
have to be reduced to very simple molecules by a combination of mechanical and
enzymatic degradation. The resulting sugars, amino acids, fatty acids and the like are then
transported across the epithelium lining the intestine into blood.

The focus of this section is to examine the "big picture" of digestive physiology and to
look at fundamental aspects of digestive system structure.

Consider for a moment a Big Mac. The purpose in your eating a Big Mac, other than
simple hedonism, is to assimlate the nutrients it represents and make them available to
build, repair and maintain your own tissues, as well as provide energy for studying and
occasional other pursuits.

You may have asked yourself - "Exactly what nutients are present in a Big Mac that I
can assimilate?" MacDonald's comes close to full disclosure in this regard, but what
they don't tell you is that in order to take advantage of these nutrients, you have to
provide the means to carefully break them down into much smaller molecules that can be
imported into blood. Luckily, your digestive system takes care of this very complex
process so efficiently that most of the time you don't even need to think about it.

At its simplest, the digestive system it is a tube running from mouth to anus. This
tube is like an assembly line, or more properly, a dissembly line. Its chief goal is to
break down huge macromolecules (proteins, fats and starch), which cannot be absorbed
intact, into smaller molecules (amino acids, fatty acids and glucose) that can be absorbed
across the wall of the tube, and into the circulatory system for dissemination around your
body.

The breakdown of foodstuffs like a Big Mac is accomplished through a combination of

mechanical and enzymatic processes. To accomplish this breakdown, the digestive tube
requires considerable assistance from accessory digestive organs such as the salivary
glands, liver and pancreas, which dump their secretions into the tube. The name
"accessory" should not be taken to mean dispensible; indeed, without pancreatic enzymes
you would starve to death in short order.

In many ways, the digestive system can be thought of as a well-run factory in which
a large number of complex tasks are performed. The three fundamental processes
that take place are:

• Secretion: Delivery of enzymes, mucus, ions and the like into the lumen, and
hormones into blood
• Absorption: Transport of water, ions and nutrients from the lumen, across the
epithelium and into blood
• Motility: Contractions of smooth muscle in the wall of the tube that crush, mix
and propel its contents

Each part of the digestive tube performs at least some of these tasks, and different regions
of the tube have unique and important specializations.

Like any well-run factory, proper function of the digestive system requires robust
control systems. Control systems must facilitate communication among different
sections of the digestive tract (i.e. control on the factory floor), and between the digestive
tract and the brain (i.e. between workers and managment). Control of digestive function
is achieved through a combination of electrical and hormonal messages which
originate either within the digestive system's own nervous and endocrine systems, as
well as from the central nervous sytem and from endocrine organs such as the
adrenal gland. Different parts of these systems are constantly talking to one another. The
basic messages are along the lines of "I just received an extraordinary load of food, so I
suggest you get prepared" (stomach to large intestine) or "For goodness sake, please
slow down until I can catch up with what you've already given me" (small intestine to
stomach).

Finally, a note about differences in digestive anatomy and physiology among

animals. The digestive systems of humans, dogs, mice, horses, kangaroos and great white
sharks are, to a first approximation, virtually identical. If you look more carefully
however, it becomes apparent that each of these species has evolved certain digestive
specializations that have allowed it to adapt to a particular diet.

These differences become particularly apparent

when you compare a carnivore like a cat with a
herbivore like a goat or a horse. Goats and horses
evolved from ancestors that subsisted on plants and
adapted parts of their digestive tracts into massive
fermentation vats which enabled them efficiently
utilize cellulose, the major carbohydrate of plants.

In contrast, cats evolved from animals that lived on

the carcasses of other animals, and have digestive
systems that reflect this history - extremely small fermentation vats and essentially no
ability to utilize cellulose. Bridging the gap between carnivores and herbivores are
omnivores like humans and pigs, whose digestive tracts attest to a historical diet that
included both plants and animals. The image above shows a young omnivore in the
company of herbivore and carnivore friends.

The digestive system is composed of the digestive or alimentary tube and accessory
digestive organs. The basic terminology used to describe parts of the digestive system is
shown below and more detailed description of each is presented in later sections.

The digestive system depicted above - a carnivore - is the simplist among mammals.
Other species, even humans, have a more or very much more extensive large intestine,
and ruminants like cattle and sheep have a large set of forestomachs through which food
passes before it reaches the stomach.

Each of the organs shown above contributes to the digestive process in several unique
ways. If you were to describe their most important or predominant function, and
summarize shamelessly, the list would look something like this:

• Mouth: Foodstuffs are broken down mechanically by chewing and saliva is added
as a lubricant. In some species, saliva contains amylase, an enzyme that digests
starch.
• Esophagus: A simple conduit between the mouth and stomach - clearly important
but only marginally interesting compared to other regions of the tube.
• Stomach: Where the real action begins - enzymatic digestion of proteins initiated
and foodstuffs reduced to liquid form.
• Liver: The center of metabolic activity in the body - its major role in the digestive
process is to provide bile salts to the small intestine, which are critical for
digestion and absorption of fats.
 • Pancreas: Important roles as both an endocrine and exocrine organ - provides a
potent mixture of digestive enzymes to the small intestine which are critical for
digestion of fats, carbohydrates and protein.
• Small Intestine: The most exciting place to be in the entire digestive system - this
is where the final stages of chemical enzymatic digestion occur and where almost
almost all nutrients are absorbed.
• Large Intestine: Major differences among species in extent and importance - in
all animals water is absorbed, bacterial fermentation takes place and feces are
formed. In carnivores, that's about the extent of it, but in herbivores like the horse,
the large intestine is huge and of critical importance for utilization of cellulose.

Microanatomy of the Digestive Tube

Remarkably diverse and specialized processes take place in different sections of the
digestive tract, but there is a fundamental consistency in the architecture of the tubular
digestive tract. From the mouth to the anus, the wall of the digestive tube is
composed of four basic layers or tunics.

• Tunica serosa is the outermost covering of the digestive tube. In most of the
digestive tract (stomach and intestines) it consists of a thin layer of loose
connective tissue covered by mesothelium (a type of squamous epithelium that
lines body cavities); within the peritoneal cavity, this structure is also referred to
as visceral peritoneum.

In the abdominal cavity, the serosa on each side of the tube fuses together to form
a suspensory structure called mesentery, which houses vascular and nervous
supplies to the digestive tract and is continuous with the lining of the cavity. In
regions outside of the abdominal cavity where the the digestive tube is essentially
affixed to adjacent structures via its outer layer of connective tissue (esophagus
and rectum), this tunic is referred to as tunica adventitia instead of tunica serosa.

• Tunica muscularis endows the digestive tube with an ability to be motile. In

most of the digestive tube, this tunic consists of two thick layers of smooth
 muscle. Muscle fibers in the inner layer are aligned circularly, whereas those in
the outer layer have a longitudinal orientation.

This combination of circular and longitudinal smooth muscle gives the tube an
ability to perform complex movements that squeeze and propel ingesta in the
lumen. Between the inner circular and outer longitudinal layers of smooth muscle
is another critical component of the digestive tract's nervous system - the
myenteric plexus.

• Tunica submucosa, immediately beneath the mucosa, is a layer of loose to dense

connective tissue containing blood and lymphatic vessels. The submucosa also
contains the submucous plexus, a critical component of the digestive tract's
nervous system which provides nervous control to the mucosa.

• Tunica mucosa is the innermost layer of the digestive tube and lines the lumen.
Among the four tunics, the mucosa is most variable in structure and
function, endowing the tube with an ability to perform diverse and
specialized digestive tasks along its length. Of critical importance in this
regard are the epithelial cells that cover the mucosa and are thus in direct
contact with the lumen.

This epithelial cell sheet (lamina epithelialis) is distinctly different in different

regions of the tract. Indeed, in most of the tract, several different cell types
contribute to the epithelium, including cells dedicated to secretion, absorption or
production of hormones.

These distinctive differences in architecture of the epithelium can be seen below

in the micrographs of mouse digestive tube. The magnification of all four images
is identical and the epithelial layer is oriented toward the top.

Beneath the epithelium, but still within the tunica mucosa is a layer - the lamina
 propria - of loose connective tissue through which course blood vessels and
lymphatics that supply the epithelium. This layer also contains lymphatic nodules
important to immune functions of the digestive tract. Finally, beneath the lamina
propropria is a thin layer of smooth muscle (lamina muscularis mucosae) which
permits the mucosa to dynamically move and fold.

Microbial Life in the Digestive Tract

The gastrointestinal tract contains an immensely complex ecology of
microorganisms. A typical person harbors more than 500 distinct species of bacteria,
representing dozens of different lifestyles and capabilities. The composition and
distribution of this menagerie varies with age, state of health and diet.

The number and type of bacteria in the gastrointestinal tract vary dramatically by
region. In healthy individuals the stomach and proximal small intestine contain few
microorganisms, largely a result of the bacteriocidal activity of gastric acid; those that are
present are aerobes and facultative anaerobes. One interesting testimony to the ability of
gastric acid to suppress bacterial populations is seen in patients with achlorhydria, a
genetic condition which prevents secretion of gastric acid. Such patients, which are
otherwise healthy, may have as many as 10,000 to 100,000,000 microorganisms per ml
of stomach contents.

In sharp contrast to the stomach and small intestine, the contents of the colon
literally teem with bacteria, predominantly strict anaerobes (bacteria that survive
only in environments virtually devoid of oxygen). Between these two extremes is a
transitional zone, usually in the ileum, where moderate numbers of both aerobic and
anaerobic bacteria are found.
Microbial Populations in the Digestive Tract of Normal Humans
Stomach Jejunum Ileum Colon
Viable bacteria per gram 0 - 103 0 - 104 105 - 108 1010 - 1012
pH 3.0 6.0-7.0 7.5 6.8-7.3
The gastrointestinal tract is sterile at birth, but colonization typically begins within
a few hours of birth, starting in the small intestine and progressing caudally over a
period of several days. In most circumstances, a "mature" microbial flora is established
by 3 to 4 weeks of age.

It is also clear that microbial populations exert a profound effect on structure and
function of the digestive tract. For example:

• The morphology of the intestine of germ-free animals differs considerably from

normal animals - villi of the small intestine are remarkably regular, the rate of
epithelial cell renew is reduced and, as one would expect, the number and size of
Peyer's patches is reduced.
 • The cecum of germ-free rats is roughly 10 times the size of that in a conventional
rat.

• Bacteria in the intestinal lumen metabolize a variety of sterols and steroids. For
example, bacteria convert the bile salt cholic acid to deoxycholic acid. Small
intestinal bacteria also have a important role in sex steroid metabolism.

Finally, bacterial populations in the large intestine digest carbohydrates, proteins

and lipids that escape digestion and absorption in small intestine. This fermentation,
particularly of cellulose, is of critical importance to herbivores like cattle and horses
which make a living by consuming plants. However, it seems that even species like
humans and rodents derive significant benefit from the nutrients liberated by intestinal
microorganisms.

"I didn't fight my way to the top of the food chain to become a vegetarian"
The diet of any animal contains hundreds if not thousands of different molecules,
but the bulk of the ingested nutrients are in the form of huge macromolecules that
cannot be absorbed into blood without first being reduced to much simpler and
smaller forms - even table sugar (sucrose) cannot be absorbed without first being
enzymatically ripped apart into glucose and fructose. The most important enzymatic
reaction in digestion of foodstuffs is hydrolysis - the breaking of a chemical bond by the
addition of a water molecule.

Proteins

Proteins are polymers of amino acids linked together by peptide bonds. Chain length
varies tremendously and many dietary proteins have been modified after translation by
addition of carbohydrate (glycoproteins) or lipid (lipoprotein) moieties. These
modifications will be almost totally ignored in this text. Very short proteins, typically 3 to
10 amino acids in length, are called peptides.

Although very small peptides can be absorbed to a limited degree, for all intents and
purposes, proteins must be reduced to single amino acids before they can be absorbed.
Enzymes that hydrolyze peptide bonds and reduce proteins or peptides to amino
acids are called proteases or peptidases.

Lipids

Fatty acids are present in only small amounts in animal and plant tissues, but are the
building blocks of many important complex lipids. True fatty acids possess a long
hydrocarbon chain terminating in a carboxyl group. Nearly all fatty acids have an even
number of carbons and have chains between 14 and 22 carbons in length. The principle
differences among the many fatty acids are the length of the chain (usually 16 or 18
carbons) and the positions of unsaturated or double bonds. For example, stearic acid
(pictured below) has 18 carbons and is saturated.

The so-called "short-chain" or volatile fatty acids are 2 to 4-carbon molecules of great
importance in intermediary metabolism and as the mainstay of ruminant nutrition. They
are represented by acetic, butyric and proprionic acids.

The most abundant storage form of fat in animals and plants, and hence the most
important dietary lipid, is neutral fat or triglyceride. A molecule of triglyceride is
composed of a molecule of glycerol in which each of the three carbons is linked through
an ester bond to a fatty acid. Triglycerides cannot be efficiently absorbed, and are
enzymatically digested by pancreatic lipase into a 2-monoglyceride and two free fatty
acids, all of which can be absorbed. Other lipases hydrolyse a triglyceride into glycerol
and three fatty acids.

A triglyceride (triacylglycerol): tristearin

Carbohydrates

The diversity of dietary carbohydrates necessitates discussion of several classes of

these molecules, ranging from simple sugars to huge, branched polymers.

Monosaccharides or simple sugars are either hexoses (6-carbon) like glucose, galactose
and fructose, or pentoses (5-carbon) like ribose. These are the breakdown products of
more complex carbohydrates and can be efficiently absorbed across the wall of the
digestive tube and transported into blood.

Disaccharides are simply two monosaccharides linked together by a glycosidic bond.

The disaccharides most important in nutrition and digestion are:

• lactose or "milk sugar": glucose + galactose

• sucrose or "table sugar": glucose + fructose
• maltose: glucose + glucose

Oligosaccharides are relatively short chains of monosaccharides which typically are

intermediates in the breakdown of polysaccharides to monosaccharides.

Polysaccharides are the most abundant dietary carbohydrate for all except very young
animals. You should be familiar with three important polysaccharides, each of which is a
large polymer of glucose:

• Starch is a major plant storage form of glucose. It occurs in two forms: alpha-
amylose, in which the glucoses are linked together in straight chains, and
amylopectin, in which the glucose chains are highly branched. Except for the
branch points of amylopectin, the glucose monomers in starch are linked via
alpha(1->4) glycosidic bonds, which, in the digestive tract of mammals, are
hydrolyzed by amylases.

• Cellulose is the other major plant carbohydrate. It is the major constituent of

plant cell walls, and more than half of the organic carbon on earth is found in
cellulose. Cellulose is composed on unbranched, linear chains of D-glucose
molecules, linked to one another by beta(1->4) glycosidic bonds, which no
vertebrate has the capacity to enzymatically digest. Herbivores subsist largely
on cellulose, not because they can digest it themselves, but because their digestive
tracts teem with microbes that produce cellulases that hydrolyze cellulose.

• Glycogen is the third large polymer of glucose and is the major animal storage
carbohydrate. Like starch, the glucose molecules in glycogen are linked together
by alpha(1->4) glycosidic bonds.