EBF 303 ENVIRONMENTAL AND ANIMAL PHYSIOLOGY

INTRODUCTION
What is Animal Physiology?
Animal physiology is the study of processes that operate in living organisms at all levels
including functions of tissues and organ systems. It also involves the study of the regulation
of processes within groups of cells and how the combined activity of cells affects the
function of the animal. Animal physiology can be studied in different ways:
Cell and molecular physiology refer to study at cellular level e.g. molecular genetics,
biochemistry, signal transduction
Systems physiology studies how cells and tissues interact to carry out specific functions e.g.
pacemaker cells in triggering heart muscle to contract
Organismal physiology is the study of the way an animal undertakes a specific process or a
behaviour e.g. metabolic rate in response to temperature
Ecological physiology is the study of how animals respond physiologically to environmental
conditions and challenges.
Integrative physiology refers to investigations with a deliberate emphasis on synthesis
across levels of biological organization, such as research that probes the relations between
molecular and anatomical features of organs. It attempts to understand physiological
processes at a variety of levels of biological organisation and across multiple systems
Comparative animal physiology is the synthetic study of the function of all animals. It
contrasts, for example, with human physiology or avian physiology, each of which addresses
only a limited set of animals. Comparative physiology is termed comparative because one of
its major goals is to compare systematically the ways that various sorts of animals carry out
similar functions, such as vision, breathing, or circulation. It enables you to identify if a
particular function is carried out by related and unrelated species in different environments .
It is also a way of assessing outcomes of evolution e.g. internalised breathing is an
adaptation for animals than live on land.
The Importance of Physiology
Physiology is one of the key disciplines for understanding
1. The fundamental biology of all animals
2. Human health and disease
3. The health and disease of nonhuman animals of importance in human affairs.
The study of physiology has enormous practical applications because physiology is a
principal discipline in the understanding of health and disease. One reason is that
nonhuman animals are often used as “models” for research that advances understanding of
human physiology.
Physiology is also important because it is one of biology’s most integrative disciplines.
Physiologists study all the levels of organization of the animal body. Physiology not only
pursues all these levels of biological organization within individual animals but also relates
this knowledge to the ecology and evolutionary biology of the animals.
DIGESTIVE SYSTEMS
General Description of digestive tract
Animal digestion evolved from an intracellular to an extracellular process in a specialized sac
or tube connected to the environment. Digestion of food inside the body but outside the
cell is accomplished by a digestive tract. Intracellular digestion is limited because only food
items small enough to be internalized by the cells can be digested, whereas extracellular
digestion permits an animal to store and break down larger varieties and quantities of food
items. The first digestive systems probably evolved as an infolding of the epidermis into an
interior sac to trap food, providing the ability to capture much larger quantities of food. This
is seen in Cnidaria (coelenterates e.g. jellies, corals, and their relatives). In later animal
groups, the sac fused with the opposite end of the body to form a complete tube with an
entrance (mouth) and exit (anus). Cells lining this digestive tube could evolve specialized
functions; for example, cells responsible for acidic digestion could be compartmentalized
and separated from those involved in alkaline digestion. Other parts of the tube could be
specialized for receiving and storing food and processing wastes (Figure 1). Indigestible
items could remain outside and not take up space within cells.
Thus, an animal’s digestive tract can be thought of as a hollow sac or a tube with an
entrance and exit, lying within the body and specialized for the initial processing of food
items. Conventionally, the gut tube in most animals can be divided into three specific
regions: the foregut, midgut, and the hindgut (Figure 1). A digestive tract with one-way
passage of food allows simultaneous operation of sequential stages in the processing of
food and reduces mixing of digested and undigested matter. The crop is a storage region
found in some animals.
Classification of animals according to Feeding Methods
Animals can be classified according to their primary feeding methods. Numerous methods
for obtaining food have evolved. These include:
• Carnivores primarily eat other animals. They specialize in capturing live prey or rely on
their abilities to locate carrion, and typically eat a high-energy, high-protein diet because of
the high percentage of muscle tissue (“meat”) in most animals.
• Herbivores depend on the intake of algal or plant materials, such as plant leaves, fruits, or
seeds. Some of these materials have comparatively little directly available energy, and
herbivores eating them have two options. The first, as seen in the cattle, uses pregastric
fermentation (the processing of foodstuffs by microbes) as a means to break down plant
material into absorbable units. In these animals the foregut is modified such that
microorganisms can proliferate in a fermentation vat, the rumen. In a second type of
herbivore, those with simple stomachs such as the horse and rabbit, microbial digestion
occurs in the hindgut, which includes the colon and cecum. Herbivores either can be
nonselective in their choice of food items or, as in the case of the panda, with its
dependence on bamboo, can be highly selective. Herbivorous fish may feed on the fruits,
seeds, flowers, and leaves of trees, whereas others may feed on algae.
• Omnivores such as humans, monkeys, and pigs can eat both animals and other organisms
such as plants or fungi, and have digestive tracts more similar to carnivore tracts that rely on
enzymatic digestion of foodstuffs. Because of seasonal changes in food availability, gut size
adapts to low-quality feeds by increasing in length. For example, the starling is primarily a
carnivore during the warmer months when insects and worms are available, but during the
harsh winter months it is forced to become a herbivore and consume low-quality foods
(buds, and so forth). In response, gut length increases a remarkable 450%.
Depending on the life cycle of some animals, feeding specializations can be related to a
particular stage of development e.g. young mammals shift from milk to an adult diet.
External food supply ultimately represents one of the key factors that determines animal
survivability, the others being predation, parasitism, disease, competition, and beneficial
symbioses (such as microbes in ruminants’ digestive tracts).
General Aspects of Digestion
Digestive systems perform four basic digestive processes: motility, secretion, digestion, and
absorption.
Motility: The term motility refers to the muscular contractions within the gut tube that mix
and move forward the contents of the digestive tract. Two basic types of digestive motility
are superimposed on this ongoing tonic activity:
• Propulsive movements propel or push the contents through the digestive tract at varying
speeds, with the rate of propulsion dependent on the functions accomplished by the
different regions; that is, food is moved forward in a given segment at an appropriate
velocity to allow that segment to “do its job.” For example, transit of food through the
esophagus of vertebrates is rapid, which is appropriate because these structures merely
serve as a passageway from the mouth to the stomach or midgut. In comparison, in the
small intestine—the major site of digestion and absorption—the contents move slowly,
allowing sufficient time for the breakdown and absorption of food. Propulsive movements
are often thought of as being unidirectional from the mouth to anal sphincter; however,
antiperistaltic contractions also occur in some species, especially birds.
• Mixing movements serve a twofold function. First, by mixing food with the digestive juices,
movements promote digestion of the food. Second, they facilitate absorption by exposing
all portions of the intestinal contents to the digestive tract’s absorbing surfaces. The motility
in the digestive tract mainly due to smooth muscle within the walls of the digestive organs is
controlled by complex autonomic (“involuntary”) mechanisms. Exceptions include the ends
of the mammalian tract—the mouth and some or all of the esophagus at the beginning and
the external anal sphincter at the end—where motility may involve skeletal muscle.
Accordingly, the acts of chewing, swallowing (rumination), and defecation have voluntary
control.
Secretion: A number of digestive juices are secreted into the digestive tract lumen by
exocrine glands located along the route, each with its own specific secretory product(s).
Each secretion consists of water, electrolytes, and specific organic constituents that are
important in the digestive process, such as enzymes, bile salts, or mucus. The secretory cells
extract large volumes of water and those raw materials necessary to produce their
particular secretion from blood. Secretion of all digestive juices requires energy, both for
active transport of some of the raw materials into the cell (others diffuse in passively) and
for synthesis of secretory products by the endoplasmic reticulum. On appropriate neural or
hormonal stimulation, the secretions are released into the digestive tract lumen. Normally,
the digestive secretions are reabsorbed in one form or another (back into the blood in
vertebrates) after they participate in digestion. Failure to do so (because of vomiting or
diarrhea, for example) results in loss of this fluid that has been “borrowed” from the
plasma.
Digestion: Digestion is the process whereby the structurally complex foodstuffs of the diet
are broken down into smaller, absorbable units by enzymes produced within the digestive
system. Complex carbohydrates, proteins, and fats are large molecules unable to cross
plasma membranes intact. So, to be absorbed from the lumen of the digestive tract into the
blood or lymph, they must be broken down into smaller nutrient molecules (although some
animals use endocytosis, for example, of whole proteins in neonatal mammals). Digestion
begins in the anterior regions of animal tracts and is accomplished for all nutrients with
enzymatic hydrolysis (“breakdown by water”). As food moves through the tract, it is
subjected to various enzymes, each of which breaks down the food molecules even further.
In this way, large food molecules are converted to simple absorbable units in a progressive,
stepwise fashion as the tract contents are propelled forward. The major molecules are as
follows:
1. Carbohydrates include the following: a. Monosaccharides (“one-sugar” molecules), such
as glucose, fructose, and galactose, very few of which are normally found in most diets.
They are the absorbable units.
b. Disaccharides (“two-sugar” molecules) are another source of dietary carbohydrate and
include sucrose (table sugar, which consists of one glucose and one fructose), trehalose (the
most important carbohydrate for flight in insects, made up of two glucose molecules in
opposite orientations), maltose (also made of two glucose molecules but in the same
orientation), and lactose (milk sugar, made up of one glucose and one galactose). They are
hydrolyzed into monosaccharides in digestive tracts synthesizing the appropriate enzymes.
c. Polysaccharides (“many-sugar” molecules), which consist of chains of interconnected
monosaccharide molecules, are the most common carbohydrates of animal diets. The most
common polysaccharides that are derived from plant sources (Figure 2b) are starch (which
has α-bonds between the glucose units) and cellulose (which has β-bonds). To be usable,
they also must be hydrolyzed into monosaccharides. Cellulose is the most abundant organic
molecule in the biosphere and is the major component of plant material, comprising over
half of the plant cell wall. However, few animals can directly exploit this energy source.
Given the fibrous “staircase” structure of cellulose resulting from its β-bond linkages (Figure
2b), it is extremely difficult to hydrolyze. In animals that use cellulose for fuel, cellulose
digestion is accomplished by symbiotic microorganisms that proliferate in the digestive tract
and that have the necessary enzymes—cellulases—to hydrolyze cellulose. These microbes
may be housed in a specific area of the gut or in special organs connected to the gut. Chitin
is the principal component of the hard exoskeleton of arthropods and, like cellulose, is
indigestible by most vertebrates. Glycogen represents the polysaccharide storage form of
glucose in animals. After digestion of a meal, unused glucose is stored as glycogen (in liver
and muscle in vertebrates).
2. Proteins consist of various combinations of amino acids held together by peptide bonds.
Through the process of digestion, proteins are degraded primarily into their constituent
amino acids as well as a few polypeptides (several amino acids linked together by peptide
bonds), both of which are the primary absorbable units for digested protein.
3. Fats: In most terrestrial food chains, dietary fat is in the form of triglycerides, which are
neutral fats, each consisting of a combination of glycerol with three fatty acid molecules
attached. During digestion, two of the fatty acid molecules split off, leaving a monoglyceride,
a glycerol molecule with one fatty acid molecule attached. Thus, the end products of fat
digestion are monoglycerides and free fatty acids, which are the absorbable units of fat.
However, in ruminant species the triglycerides are degraded mostly to free fatty acids and
glycerol, with the glycerol being fermented. For this reason, glycerol synthesis must occur to
a greater extent than in other species. Nucleic acids can also form a significant portion of
ingested nitrogen. Pancreatic nucleases, RNase and DNase, split the nucleic acids into their
component nucleotides. The duodenum of ruminants is particularly effective in digesting
nucleic acids because approximately 20% of the nitrogen entering the abomasum (acid-
secreting portion of the stomach) originates from the microorganisms spilled from the
rumen.
Absorption: After digestion is completed, the process of absorption occurs in the middle to
posterior sections of most digestive systems (such as the small intestine in vertebrates).
Here the small, absorbable units that result from digestion, along with water, vitamins, and
electrolytes, are transferred from the digestive tract lumen into the blood or hemolymph or
body cavity.
The digestive system
The digestive system of an animal consists of the digestive tract plus the accessory digestive
organs. In addition to its role in the digestive process, additional functions of the tract
include osmoregulation, endocrine secretions, immune function, and the elimination of
toxins. The digestive (or gastrointestinal) tract of most vertebrates includes the following
organs (Figure 3): mouth; pharynx (throat); esophagus; stomach (and rumen in ruminants),
or proventriculus-gizzard complex in birds; small intestine; large intestine; and anus. Note
that these organs are continuous with each other and are discussed as separate entities only
because of their regional modifications, which allow them to specialize in particular
digestive activities. In addition to the specialized gut tubes, the accessory digestive organs of
most vertebrates include the salivary glands, the exocrine pancreas, and the biliary system,
which consists of the liver and, in some species, the gallbladder (Figure 3). These exocrine
organs are located outside of the wall of the digestive tract and empty their secretions
through ducts into the digestive tract lumen. They develop from outpocketings of the
embryonic digestive tube and maintain their connection with the digestive tract through the
ducts that are formed.

Mouth
There is considerable diversity in the mechanisms and behaviors for obtaining food because
of the enormous variety of animal diets.
1. Obtaining and Receiving Food: Animals may use shredding and cutting devices, such as
bony teeth in many vertebrates, or specialized appendages as in many arthropods. An
example, Lophiiformes—a marine group that includes goosefishes, frogfishes, and
anglerfishes use modifications in their first dorsal fin to function as a lure to attract
potential prey. The mouth (or oral cavity) itself, which initially receives the food entering
the gut, may also be specialized. The mouth of a snake, for example, requires unique
adaptations to swallow a meal up to 1.5 times the snake’s own body weight. A snake’s
jaw can open to an angle of up to 130 degrees, whereas a human’s jaw can be opened
only 30 degrees. Snakes have a hinged jaw as opposed to the single bone found in
mammals. The snake’s lower jaw is also split into two parts, with the halves connected by
an elastic ligament, which permits the snake to completely stretch its head around its
victim’s body. Powerful muscles in the cheek and throat steadily push its prey head first
toward the esophagus helped in part by the backward curvature of the teeth.
Although ancient birds had teeth (found as fossils), modern birds lack them, but their
beaks are often specialized for teethlike functions. The beak represents one of the more
evolutionarily plastic components of the avian digestive system, having been molded to
conform to particular feeding habits. In herbivorous birds, the beak is an enlarged,
crushing forceps, whereas in carnivorous birds the beak is a sharp-edged tearing
instrument. The beaks (bills) of some birds, including ducks and geese, are richly
innervated with sensory endings. In mammals, the mouth is ringed by the muscular lips,
which aid in prehension, the seizing and conveying of food to the mouth. For example,
the horse uses its lips to move foodstuffs into the mouth. The palate, which forms the
arched roof of the oral cavity, separates the mouth from the nasal passages. Its presence
allows breathing and chewing or sucking to take place simultaneously. Toward the front
of the mouth, the palate is made of bone, forming what is known as the hard palate,
There is no bone in the portion of the palate toward the rear of the mouth; this region is
called the soft palate, However, in most avian species there is no soft palate, but the hard
palate is separated by a median slit that permits direct communication with the nasal
cavities. The floor of the avian mouth is membranous and, in some species such as
pelicans, serves a storage capacity. In some primates, including humans, hanging down
from the soft palate at the rear of the throat is a dangling projection, the uvula, which
plays an important role in sealing off the nasal passages during swallowing. The tongue,
which forms the floor of the oral cavity, consists of voluntarily controlled skeletal muscles
that form a muscular hydrostat. Methods of obtaining food and drink vary considerably;
 for example, the ballistic tongue of most lizards relies on simple surface tension
(stickiness created when a wet tongue contacts dry prey) to catch prey. However, the
tongue pouch of the chameleon functions more like a suction cup as it is capable of
consuming prey much larger than what simple surface tension could handle. In ruminant
mammals, the tongue is the organ of prehension because the lips have limited motility
and the upper incisor teeth are absent. A giraffe can wrap its 46-cm (18-inch) tongue
around a leafy branch and tear the leaves off into its mouth. Tongues can also be used for
drinking. Cats and dogs, for example, curl their tongues downward into water, then pull it
up rapidly to create a rising column of water. The jaws then snap over the column to
engulf it before it falls back. A domestic cat can do this four times per second!
Movements of the tongue are important in guiding food within the mouth during
chewing and swallowing, and also play an important role in vocalization. Embedded
within the tongue are the taste buds, which are also dispersed in the soft palate, throat,
and linings of the cheeks. The tongue also continually synthesizes an antimicrobial
peptide. For this reason, tongues are rarely infected and heal quickly after injury.
2. Mastication: The first step in the digestive process is mastication (chewing), the motility
of the mouth that involves slicing, tearing, grinding, and mixing ingested foods by
specialized mouthparts such as teeth. The purposes of mastication are
(1) to grind and break food up into smaller pieces to facilitate swallowing and to increase
the food surface area on which salivary enzymes will act,
(2) to mix food with saliva, and
(3) to stimulate the taste buds, which reflexly increases salivary, gastric, pancreatic, and bile
secretion to prepare for the arrival of food in the lower digestive tract.
However, carnivores normally swallow food without chewing and mixing the contents with
saliva. Ruminants chew the feed only briefly before swallowing, sufficiently grinding the
forage into particles just small enough to be formed into a food bolus. Only when ruminants
regurgitate (movement of a food bolus from the stomach back to the mouth) is the food
then thoroughly masticated. In contrast, the horse thoroughly masticates its food prior to
swallowing.
Functions of teeth
The exposed part of a tooth is covered by enamel, the hardest structure in most
vertebrates. Teeth in fish, amphibians, and reptiles are specialized for holding and tearing
food. Polyphydontia, the replacement of teeth throughout an animal’s lifetime, occurs in
dinosaurs, sharks, and non-avian reptiles. Tooth replacement varies considerably among
species and age. For example, it occurs every two weeks in most sharks, but about every
two years in an adult crocodile.
Mammals have incisors (cutting teeth) in front to grab and hold food and flat molars in the
back for grinding fibrous material. Carnivorous mammals are noted for sharp canines (next
to incisors) for seizing, piercing, and tearing prey. Finally, there are premolars between
canines and molars, with intermediate properties. As an example, all Old World primates
(including humans) have 8 incisors, 4 canines, 8 premolars, and 12 molars. The extent to
which molars are used varies between species and is related to the composition of the diet.
(a) Simple up-and-down movements of molars in carnivores and omnivores are used for
grinding (b) herbivores make lateral grinding movements of the jaw to grind tough, coarse
feeds. The upper jaw is slightly wider than the lower jaw, and the animal masticates on one
side of the mouth at a time. Because of the lateral jaw movement, premolars may develop
sharp edges that interfere with chewing or may injure the tongue or cheeks. This problem in
domestic herbivores can be corrected by “floating the teeth,” that is, filing the projections
down. Herbivores also have a long diastema, or gap, between the front teeth and the
premolars on each side that allow ready manipulation of food by the tongue. (c) Ruminants
have a unique dentition; the upper incisors and canines are absent, while the lower incisors
bite against a hard gum or dental pad in the upper jaw. They manipulate forage into the
mouth with the tongue and lips and then cut or tear it with their lower incisors and dental
pads. The teeth of rabbits, and the lower incisors of possums, koalas and rodents, grow
continually throughout their lifetime, a consequence of abrasive high fiber diets, which
continually wear down the enamel coating. Teeth can evolve other roles, such as prey-
paralyzing venomous fangs in snakes. Not all vertebrates rely on teeth. Teeth in embryonic
baleen whales (Mysticeti) are vestigial and are reabsorbed and replaced with long plates of
baleen (parallel, fused fi laments of keratin, the protein of hair) that hang from the jaws in
place of teeth. These are used as straining devices for filter feeding, primarily on small
marine animals such as crustaceans and fish.
Saliva
Saliva aids in mastication but plays a more important role in lubricating food boluses before
swallowing. Saliva, the secretion associated with the mouth, is produced by salivary glands,
which are located outside the oral cavity and discharge saliva through short ducts into the
mouth. The functions of saliva include the following:
1. Moistening: Saliva facilitates swallowing by moistening food particles, thereby holding
them together, and by providing lubrication through the presence of mucus. Saliva
keeps the oral cavity moist (and aids in vocalization by facilitating movements of the lips
and tongue).
2. Digestion: In most animals (excluding ruminants), saliva begins digestion of starch in the
mouth through action of salivary amylase, an enzyme that breaks down starches into
maltose, a disaccharide consisting of two glucose molecules.
3. Defense: Saliva in many vertebrates exerts some antibacterial action by means of a
twofold effect—first by lysozyme, an enzyme that lyses certain bacteria by breaking
down their cell walls; second, by salivary agglutin, a glycoprotein that complexes with
IgA antibodies and then binds to bacteria; third, by lactoferrin, which tightly binds to
iron needed for bacterial multiplication; and fourth, by rinsing away material that may
serve as a food source for bacteria.
4. Taste: Saliva is a solvent for molecules that stimulate the taste buds.
5. Neutralization: Saliva is often rich in bicarbonate buffers, which neutralize acids in food
as well as acids produced by bacteria in the mouth. In ruminants, salivary bicarbonate is
 responsible for neutralizing the pH of rumen fluid and is an important buffering system
for maintaining the acid–base equilibrium of the rumen contents.
6. Thermoregulation: Saliva can also be used as a means of temperature control in animals
without sweat glands. In fact, most mammals and birds have no sweat glands and rely
on panting as a means of evaporative cooling. Kangaroos actually spread saliva over
their bodies when outside temperatures approach lethal limits.
7. Poisons: Venomous reptiles have special oral glands (associated with fangs) that
produce highly toxic secretions, which, once injected into prey, exert hemotoxic
(affecting the circulatory system), neurotoxic (affecting the nervous system and brain),
or myotoxic (muscle necrosis) effects. Venoms are approximately 90% proteins and
most are enzymes. These components act rapidly to prevent the prey from escaping.
8. Anticoagulation: e.g. secretion of anticoagulants in blood-sucking vampire bats.
9. Pheromones: The salivary glands of some vertebrates release these external hormones.
For example, male boars stimulated by a receptive female will produce copious
amounts of saliva laden with androsterones. These stimulate the female to take a
mating posture and may warn off other boars.
Fish and chickens do not have serous cells, so their total daily output of saliva is
comparatively small, and it lubricates the food in preparation for swallowing; wetting occurs
later, in the crop. The salivary glands of ruminants produce copious amounts of alkaline
saliva. When swallowed, this saliva enables selective compartments of its stomach to house
a population of microbes capable of digesting dietary cellulose. In nonruminant mammals,
saliva is ultimately not as critical for digesting and absorbing foods, because enzymes
produced by the pancreas and small intestine can digest food even in the absence of salivary
and gastric secretion. Salivary secretion in vertebrates is the only digestive secretion entirely
under neural control. Saliva in mammals is continuously secreted, even in the absence of
apparent stimuli, because of constant low-level stimulation by the parasympathetic nerve
endings that terminate in the salivary glands. This basal secretion is important in keeping
the mouth and throat moist at all times. The basal rate of salivary secretion in humans is
about 0.5 mL/ min, which can increase to 5 mL/min in response to a potent stimulus such as
sucking on a lemon. Remarkably, salivary secretion in ruminants is of such a magnitude that
it can be regarded as a second circulatory system for body fluids and electrolytes. Cattle
produce approximately 140 liters of saliva per day, whereas sheep and ponies secrete
around 10 liters per day. Digestion in the mouth is minimal Most digestion of foodstuffs in
vertebrates is accomplished farther down the tract after the swallowing.
Pharynx, Esophagus, and Crop
The pharynx (throat) is the cavity at the rear of the oral cavity. In vertebrates, it acts as a
common passageway for both the digestive system (by serving as the link for passing food
between the mouth and esophagus) and the respiratory system (as a path for water moving
across gills, or by providing access between the nasal passages and trachea for air). This
arrangement necessitates mechanisms to guide food and air into the proper passageways
beyond the pharynx. Swallowing in vertebrates is a sequentially programmed all-or-none
reflex. Swallowing actually is the entire process of moving food from the mouth through the
esophagus into the stomach. Swallowing in a vertebrate is initiated when a bolus, or ball of
food, is forced by the tongue to the rear of the mouth into the pharynx. The pressure of the
bolus in the pharynx stimulates pharyngeal pressure receptors, which send afferent
impulses to the swallowing center located in the medulla. This center then reflexly activates,
in the appropriate sequence, the muscles that are involved in swallowing. Once initiated,
swallowing cannot be stopped. Swallowing is arbitrarily divided into two stages: the
oropharyngeal stage and the esophageal stage. The oropharyngeal stage consists of moving
the bolus from the mouth through the pharynx and into the esophagus. When the bolus
enters the pharynx during swallowing, it must be directed into the esophagus and
prevented from reentering the mouth, from entering the nasal passages, and trachea
(where it causes choking) (Figure 4).
The esophagus is a muscular tube guarded by sphincters at both ends. It is a fairly straight,
muscular tube that extends between the pharynx and stomach. In ruminants and dogs, the
entire musculature of the esophagus is skeletal, whereas in birds and humans it is entirely
smooth muscle. Lying for the most part in the thoracic cavity, the esophagus joins the
stomach in the abdominal cavity. The esophagus is guarded at the upper end by the
pharyngoesophageal sphincter and at the lower end by the gastroesophageal sphincter (or
cardiac sphincter). Except during a swallow, the pharyngoesophageal sphincter remains
closed as a result of neurally induced tonic contraction of the sphincter’s circular skeletal
muscle. This keeps the entrance to the esophagus closed to prevent large volumes of air
from entering the esophagus and stomach during breathing. Otherwise, the digestive tract
would be subjected to large volumes of gas, which would lead to excessive burping. During
swallowing, this sphincter opens and allows the bolus to pass into the esophagus. Once the
bolus has entered the esophagus, the pharyngoesophageal sphincter closes, the respiratory
airways are opened, and breathing resumes. Ruminants have another valve. Most of these
gases are diverted from the rumen into the trachea by the closing of the nasopharyngeal
sphincter, the junction between the nasal cavity and the throat. Most of the gases are
ultimately expelled with normal respiratory activity. After the oropharyngeal stage, the
esophageal stage of the swallow begins once the food bolus contacts the pharyngeal
mucosa. The swallowing center initiates a primary peristaltic wave that sweeps from the
beginning to the end of the esophagus, forcing the bolus ahead of it through the esophagus
to the stomach. The term peristalsis refers to ring-like contractions of the circular smooth
muscle that move progressively forward, pushing the bolus ahead of the contraction. If a
large or sticky swallowed bolus fails to be carried along to the stomach by the primary wave
of peristalsis, the lodged bolus distends the esophagus, stimulating pressure receptors
within its walls and thus initiating a second, more forceful peristaltic wave that is mediated
by the intrinsic nerve plexuses at the site. Distension of the esophagus also reflexly
increases salivary secretion. The trapped bolus is eventually dislodged and moved forward
through the combination of lubrication by the extra swallowed saliva and the forceful
secondary waves. Except during swallowing, the gastroesophageal sphincter remains
contracted, to maintain a barrier between the stomach and esophagus, reducing the
possibility of reflux of acidic gastric contents into the esophagus. If gastric contents do flow
back into the esophagus despite the sphincter, the acidity of these contents irritates the
esophagus, causing the esophageal discomfort known in humans as heartburn. The
gastroesophageal sphincter relaxes reflexly as the peristaltic wave sweeps down the
esophagus so that the bolus can pass into the stomach. After the bolus has entered the
stomach, the gastroesophageal sphincter again contracts. In most vertebrates, mucus is
secreted throughout the length of the entire digestive tract. This lubricates the food, lessens
the likelihood that the esophagus will be damaged by any sharp edges in the newly entering
food, and protects the esophageal wall from acid and enzymes in gastric juice if gastric
reflux occurs.
The crop is a modified section of the esophagus and functions mainly as a storage organ.
The crop in domestic fowl is structurally identical to that of the esophagus except for a
scarcity of mucus glands. Mucus glands are also relatively sparse in the region of the
esophagus below the crop because movement of the bolus largely involves prewetted
material from the crop. Granivorous (“grain-eating”) and fish-eating birds have
comparatively large crops for food storage, whereas carnivorous and insectivorous birds
have limited need for a crop, which therefore are considerably reduced in size or are absent.
A food bolus moving down the esophagus in crop-bearing animals has two possibilities. It
can either continue on to the proventriculus-gizzard organ(s) (in most birds), or it can enter
the crop for temporary storage. The stored food is moistened by water as the animal drinks,
but essentially no digestion occurs here.
Stomach or Midgut
In most animals, the midgut or stomach provides for the initial digestion (beyond the minor
salivary contribution) and storage of ingested food items. The vertebrate stomach stores
food, begins protein digestion, and forms chyme. In vertebrates, only some species of bony
fish, lampreys, hagfishes, and larval toads completely lack a stomach, with the esophagus
opening directly into the intestine. In monogastric mammals, the stomach is a simple,
muscular, saclike chamber lying between the esophagus and small intestine. Generally, the
stomach of amphibians, fish, reptiles, and most mammals is a simple tubular expansion of
the digestive tract. In humans it is arbitrarily divided into three sections based on anatomic,
histologic, and functional distinctions (Figure 6). The dorsal region, or the fundus, is
responsible for the storage of ingested food and adaptation to changes in volume. The
middle, or main, part of the stomach is the body or corpus, Here the digesta is mixed with
gastric secretions. The smooth muscle layers in the fundus and corpus are relatively thin,
but the lower portion of the stomach, the antrum, has a much heavier musculature that is
used to regulate expulsion of food into the small intestine as well as mix the contents. The
terminal portion of the stomach consists of the pyloric sphincter, which acts as a barrier
between the stomach and the upper part of the small intestine, the duodenum. The
stomach performs three main functions:
 1. Storage: The most important function is to store ingested food until it can be emptied
into the small intestine at a rate appropriate for optimal digestion and absorption. In only
a matter of minutes carnivores can consume a meal that then takes hours to digest and
absorb. Because the small intestine is the primary site for this digestion and absorption, it
is important that the stomach store the food and meter it into the duodenum at a rate
that does not exceed the small intestine’s capacities.
2. Digestion: The stomach secretes hydrochloric acid (HCl) and enzymes that begin
protein digestion.
3. Chyme formation: Through mixing movements, the ingested food is pulverized and
mixed with gastric secretions to produce a thick, liquid mixture known as chyme, The
stomach contents must be converted to chyme before they can be emptied into the
duodenum.
How the stomach accomplishes the four basic digestive processes
Gastric motility is complex and subject to multiple regulatory inputs. The four aspects of
gastric motility are (1) gastric filling, (2) gastric storage, (3) gastric mixing, and (4) gastric
emptying.
Gastric filling involves receptive relaxation. Stomachs can have a remarkable ability to
accommodate significant changes in volume. By comparison, the empty human stomach has
a volume of about 50 mL, but it can expand to a capacity of about 1 liter (1,000 mL) during a
meal. The mammalian stomach can accommodate such a 20-fold change in volume with
little tension in its walls and little rise in intragastric pressure through the following
mechanism. The interior of the stomach is thrown into deep folds. During a meal, the folds
get smaller and flatten out as the stomach relaxes slightly with each mouthful. This reflex
relaxation of the stomach as it is receiving food is called receptive relaxation; it enables the
stomach to accommodate the extra volume of food with little rise in stomach pressure.
Receptive relaxation is triggered by the act of eating and is mediated by the vagus nerve.
Gastric storage takes place in the body of the stomach. Food is gradually fed from the body
into the antrum, where mixing does take place. The strong antral peristaltic contractions are
responsible for mixing food with gastric secretions to produce chyme. Gastric emptying is
largely controlled by factors in the duodenum. In addition, to accomplishing gastric mixing,
the antral peristaltic contractions provide the driving force for gastric emptying (Table 7).
Factors in the Stomach that Influence the Rate of Gastric Emptying
The main gastric factor that influences the strength of contraction is the amount of chyme,
as well as the chyme’s fluidity, in the stomach
Factors in the Duodenum that Influence the Rate of Gastric Emptying
Despite these gastric influences, factors in the duodenum are of primary importance in
controlling the rate of gastric emptying. The duodenum must be ready to receive the chyme
and can act to delay gastric emptying by reducing peristaltic activity in the stomach until the
duodenum is ready to accommodate more chyme. Even if the stomach is distended and its
contents are in a liquid form, it cannot empty until the duodenum is ready to process the
chyme. The four most important factors in the duodenum that influence gastric emptying
are fat, acid, hypertonicity, and distension.
Fat: Fat is digested and absorbed more slowly than the other nutrients. Furthermore, fat
digestion and absorption take place only within the small-intestine lumen. Therefore, when
fat is already present in the duodenum, further gastric emptying of more fatty stomach
contents into the duodenum is prevented until the small intestine has processed the fat
already there.
• Acid: Because the stomach secretes hydrochloric acid (HCl), highly acidic chyme is emptied
into the duodenum, where it is neutralized by sodium bicarbonate (NaHCO3) secreted into
the duodenal lumen from the pancreas. Unneutralized acid irritates the duodenal mucosa
and inactivates the pancreatic digestive enzymes that are secreted into the duodenal lumen.
Appropriately, therefore, unneutralized acid in the duodenum inhibits further emptying of
acidic gastric contents until complete neutralization is accomplished.
• Hypertonicity: As molecules of protein and starch are digested in the duodenal lumen,
large numbers of amino acid and glucose molecules are released. If absorption of these
amino acid and glucose molecules does not keep pace with the rate at which protein and
carbohydrate digestion proceeds, these large numbers of molecules remain in the chyme
and increase the osmolarity of the duodenal contents. Because water is freely diffusible
across the duodenal wall, water enters the duodenal lumen from the plasma as the
duodenal osmolarity rises. Large volumes of water entering the intestine from the plasma
lead to intestinal distension, and, more importantly, circulatory disturbances ensue because
of the reduction in plasma volume. To prevent these effects, gastric emptying is reflexly
inhibited when the osmolarity of the duodenal contents starts to rise. Thus, the amount of
food entering the duodenum for further digestion into a multitude of additional osmotically
active particles is reduced until absorption processes have had an opportunity to catch up.
Vomiting
Vomiting, or emesis is the forceful expulsion of gastric contents out through the mouth. The
stomach itself does not actively participate in the act of vomiting. The stomach, the
esophagus, the esophageal sphincters, and the pyloric sphincter are all relaxed during
vomiting. The major force for expulsion comes from contraction of the respiratory muscles
(the diaphragm and abdominal muscles). Vomiting, however, is unusual in horses because
the tone of the gastroesophageal sphincter is so great that it limits regurgitation of
materials into the esophagus. Rats, too, cannot vomit and are careful to taste novel foods in
small quantities. Some species of birds, particularly carnivores, can “vomit” or egest
indigestible foodstuffs. Owls, for example, egest the bones, feathers, and fur of their prey in
the form of pellets. Vomiting in mammals begins with a deep inspiration and closure of the
glottis. The contracting diaphragm descends downward on the stomach while simultaneous
contraction of the abdominal muscles compresses the abdominal cavity, increasing the
intra-abdominal pressure and forcing the abdominal viscera upward. As the flaccid stomach
is squeezed between the diaphragm from above and the compressed abdominal cavity from
below, the gastric contents are forced into the esophagus and out through the mouth. The
glottis and uvula (in some primates) move to their blocking positions to prevent vomited
material from entering the respiratory airways. This complex act of vomiting is coordinated
by a vomiting center in the medulla of the brain stem. Vomiting can be initiated by afferent
input to the vomiting center from a number of receptors throughout the body. The causes
of vomiting include (1) irritation or distension of the stomach and duodenum, and (2)
chemical agents, including drugs or noxious substances that initiate vomiting (that is,
emetics) either by acting in the upper portions of the gastrointestinal tract, or by stimulating
chemoreceptors in a specialized chemoreceptor trigger zone in the medulla. Activation of
the trigger zone initiates the vomiting reflex. With excessive vomiting, an animal
experiences considerable loss of secreted fluids and acids that normally would be
reabsorbed. The resultant reduction in plasma volume can lead to dehydration and
circulatory problems, whereas loss of acid from the stomach can lead to metabolic alkalosis.
However, limited vomiting brought about by irritation of the digestive tract can provide a
useful service in removing noxious material from the stomach. Snakes, for example, that
swallow too large a prey item are sometimes forced to vomit the remains before they
putrefy inside their guts.
Secretion
The cells responsible for gastric secretion in a mammal are located in the lining of the
stomach, the gastric mucosa, which is divided into two distinct areas whose distribution
varies between species: (1) the oxyntic mucosa, which lines the body and fundus, and (2)
the pyloric gland area (PGA), which lines the antrum. The luminal surface of the stomach is
pitted with deep pockets formed by infoldings of the gastric mucosa. The invaginations in
this first portion are called gastric pits, at the base of which lie the gastric glands, A variety
of secretory cells line these invaginations, some exocrine and some endocrine or paracrine
(Figure 8). Two types of glands normally line the proventriculus of birds: simple mucosal
glands that secrete mucus in addition to compound submucosal glands that secrete HCl and
pepsinogen. Interestingly, unlike in mammals, both HCl and pepsinogen are synthesized
within the same cell—the chief or oxynticopeptic cell, Oxynticopeptic cells also line the
stomach of fish.
Gastric Exocrine Secretory Cells
Three types of secretory cells are found in the walls of the pits in the oxyntic mucosa:
• Mucous cells line the gastric pits and the entrance of the glands. They secrete a thin,
watery mucus.
• Chief and parietal cells line the deeper portions of the gastric glands. The more numerous
chief cells secrete the enzyme precursor pepsinogen.
• The parietal (or oxyntic) cells, which secrete HCl and gastric intrinsic factor. The parietal
cells are located on the outer wall of the gastric pits and do not come into contact with the
pit lumen. (Parietal means “wall,” a reference to the location of these cells. Oxyntic means
“sharp,” a reference to these cells’ potent HCl secretory product.) These exocrine secretions
are all released into the gastric lumen. Collectively, they make up the gastric digestive juice.
Between the gastric pits, the gastric mucosa is covered by surface epithelial cells, which
secrete a thick, viscous, alkaline mucus that forms a visible protective layer several
millimeters thick over the surface of the mucosa.
Gastric Endocrine and Paracrine Secretory Cells
Other secretory cells in the gastric mucosa release endocrine and paracrine regulatory
factors instead of products involved in the digestion of nutrients in the gastric juice lumen.
These are as follows:
• Enterochromaffin-like (ECL) cells dispersed among the parietal and chief cells in the
gastric glands of the oxyntic mucosa secrete the paracrine histamine.
• The gastric glands of the PGA primarily secrete mucus and a small amount of pepsinogen;
no acid is secreted in this area, in contrast to the oxyntic mucosa. More importantly,
endocrine cells known as G cells in the PGA secrete the hormone gastrin into the blood.
• D cells, which are scattered in glands near the pylorus but are more numerous in the
duodenum, secrete the paracrine somatostatin.
Hydrochloric Acid Secretion: The parietal cells actively secrete HCl into the lumen of the
gastric pits, which in turn empty into the lumen of the stomach. Although HCl does not
actually digest anything and is not absolutely essential to gastrointestinal function, it does
perform several functions.
• Activates the enzyme precursor pepsinogen to an active enzyme, pepsin, and provides an
acid medium that is optimal for pepsin activity.
• Aids in the breakdown of connective tissue and muscle fibers, thereby reducing large food
particles into smaller particles.
• Denatures protein; that is, it uncoils proteins from their tertiary structure, thus exposing
more of the peptide bonds for enzymatic attack.
• Along with salivary lysozyme, kills most microorganisms ingested with the food (although
some resistant ones may escape and continue to grow and multiply in the intestine).
Pepsinogen
The major digestive constituent of gastric secretion is pepsinogen, an inactive enzymatic
molecule produced in all vertebrates having stomachs except cyclostomes. When
pepsinogen is secreted into the gastric lumen, HCl cleaves off a small fragment of the
molecule, converting it to the active form of the enzyme, pepsin. Once formed, pepsin acts
on other pepsinogen molecules to produce more pepsin. Only when there is no more
protein in the stomach does the secretion of pepsinogen cease. Pepsin initiates protein
digestion by splitting certain amino acid linkages in proteins to yield peptide fragments.
Because pepsin can digest protein, it must be stored and secreted in an inactive form, so it
does not digest proteins such as cytoskeletons in the cells in which it is formed.
Stomach mucus
The surface of the gastric mucosa is covered by a layer of mucus, which serves as a
protective barrier against several forms of potential injury to the gastric mucosa:
• By virtue of its lubricating properties, mucus protects the gastric mucosa against
mechanical injury.
• Mucus helps protect the stomach wall from self digestion because pepsin is inhibited
when it comes in contact with the mucus coating the stomach lining. (However, mucus does
not affect pepsin activity in the lumen, where digestion of dietary protein proceeds without
interference.)
• Being alkaline, mucus helps protect against acid injury by neutralizing HCl in the vicinity of
the gastric lining, but it does not interfere with the function of HCl in the lumen.
Four chemical messengers primarily influence the secretion of gastric digestive juices.
Parietal cells have separate receptors for each of these messengers. Three of them—
acetylcholine (ACh), gastrin, and histamine—are stimulatory. They bring about increased
secretion of HCl. The fourth regulatory agent—somatostatin— inhibits acid secretion.
Gastrin and ACh also increase pepsinogen secretion through their stimulatory effect on the
chief cells.
Digestion
Carbohydrate digestion continues in the body of the stomach, whereas protein digestion
begins in the antrum. Two separate digestive processes take place within the stomach. Food
in the body of the stomach remains a semisolid mass because peristaltic contractions in this
region are too weak for mixing to occur. Because food is not mixed with gastric secretions in
the body of the stomach, very little protein digestion occurs here. Acid and pepsin can
attack only the surface of the food mass. Carbohydrate digestion, however, continues in the
interior of the mass under the influence of salivary amylase. Digestion by the gastric juice
itself is accomplished in the antrum of the stomach, where the food is thoroughly mixed
with HCl and pepsin, initiating protein digestion. In most vertebrates, at this point, fat
digestion has not even begun.
The proventriculus and gizzard begin the process of digestion in birds. Birds have no
stomach, but rather an organ is divided into two components: the proventriculus, which
serves as the “glandular stomach,” and a separate gizzard, which serves as the “muscular
stomach” to macerate and grind the ingesta. The proventriculus is comparatively small in
herbivorous birds and is considerably larger in aquatic carnivores, which also use it as a
storage space for captured prey. Motility functions of the proventriculus are to expel ingesta
and digestive secretions into the gizzard. Two pairs of thin and thick smooth muscle groups,
encircle the gizzard and act in opposition to each other. Most birds cannot chew their food,
so the gizzard, which contains grit (swallowed pebbles and small stones), is responsible for
the mechanical breakdown of ingesta. The mucosal lining of the gizzard is covered by a
coating, koilin, which forms the gizzard teeth (the abrasive lining of the gizzard’s surface).
Digesta from the gizzard is refluxed back into the proventriculus for further digestion and
mixed with gastric secretions. Movement of digesta from the gizzard back into the
proventriculus allows feed to be exposed to digestive enzymes and low pH for extended
times, consequently improving digestive efficiency and increasing gut health. Gut health
improvements are also associated with the acidic destruction of pathogenic bacteria that
are ingested with feed. In domestic poultry, gastroduodenal motility is tightly coordinated
and begins with contraction of the thin, circular muscles lining the gizzard, followed by
several waves of peristalsis in the duodenum. A powerful contraction of the thick muscles
then precedes peristalsis of the proventriculus. At the end of the contraction of the thin
muscles, ingesta flows from the gizzard into the duodenum, whereas after contraction of
the thick muscles, the ingesta flows into the proventriculus. Contraction of the
proventriculus then forces material back into the gizzard. In poultry, these cycles are
normally repeated two to three times per minute, with food deprivation decreasing the
frequency of contractions. Gizzards are also found in alligators, crocodiles, and in several
species of fish.
Digestive Accessory Organs (Pancreas, Liver, Gallbladder, Fat Body)
When gastric contents are emptied into the vertebrate small intestine, they are mixed not
only with juice secreted by the small-intestine mucosa but also with the secretions of the
exocrine pancreas and liver that are emptied into the duodenal lumen.
The (hepato)pancreas
The pancreas in most vertebrates is a mixed gland that contains both exocrine and
endocrine tissue (Figure 9). Approximately 98% of the vertebrate pancreas is committed to
its exocrine function. The predominant exocrine portion consists of grapelike clusters of
secretory cells that form sacs known as acini, which connect to ducts that eventually empty
into the duodenum. The smaller endocrine portion consists of isolated islands of endocrine
tissue, the islets of Langerhans, which are dispersed throughout the pancreas. The most
important hormones secreted by the islet cells are insulin and glucagon. The
hepatopancreas of fishes contains cells with functions comparable to those found in the
mammalian pancreas and liver. The exocrine pancreas in most vertebrates secretes a
pancreatic juice consisting of two components: (1) pancreatic enzymes actively secreted by
the acinar cells that form the acini and (2) an aqueous alkaline solution actively secreted by
the duct cells that line the pancreatic ducts. The aqueous (watery) alkaline component is
rich in sodium bicarbonate (NaHCO3). Pancreatic secretions show various adaptations to the
diet of the animal as well as the feeding strategy. Like pepsinogen, pancreatic enzymes are
produced and stored within zymogen granules and are released by exocytosis as needed.
The acinar cells secrete different types of pancreatic enzymes that can digest foodstuffs. In
nonruminants, these pancreatic enzymes are important because they can almost completely
digest food in the absence of all other digestive secretions. The principal types of vertebrate
pancreatic enzymes are (1) proteolytic enzymes, which are involved in protein digestion; (2)
pancreatic amylase and chitinase (in some vertebrates), which contributes to carbohydrate
digestion; and (3) pancreatic lipase, for fat digestion.
Pancreatic Proteolytic Enzymes: The three major proteolytic enzymes secreted by the
vertebrate pancreas are trypsinogen, chymotrypsinogen, and procarboxypeptidase, each of
which is secreted in an inactive form. When trypsinogen is secreted into the duodenal
lumen, it is activated to its active enzyme form, trypsin, by an enzyme, enterokinase. Trypsin
then autocatalytically activates more trypsinogen. Like pepsinogen, trypsinogen must
remain inactive within the pancreas to prevent this proteolytic enzyme from digesting the
cells in which it is formed. As further protection, the pancreatic tissue also produces a
chemical known as trypsin inhibitor, which blocks trypsin’s actions if activation of
trypsinogen inadvertently occurs within the pancreas. Chymotrypsinogen and
procarboxypeptidase, the other pancreatic proteolytic enzymes, are converted by trypsin to
their active forms, chymotrypsin and carboxypeptidase, respectively, within the duodenal
lumen. Thus, once enterokinase has activated some of the trypsin, trypsin then governs the
rest of the activation process. Each of these proteolytic enzymes attacks different peptide
linkages. The end products that result from this action are a mixture of amino acids and
small peptide chains. Mucus secreted by the intestinal cells protects against digestion of the
small-intestine wall by the activated proteolytic enzymes.
Pancreatic Amylase: Like salivary amylase, pancreatic amylase plays an important role in
carbohydrate digestion by converting polysaccharides into disaccharides. Amylase is
secreted in the pancreatic juice in an active form because active amylase does not present a
danger to the secretory cells.
Pancreatic Chitinase: Chitin consists of chains of glucose molecules, each linked by β-bonds,
and each of which has an acetylamino group (–N–CO–CH3) in place of a hydroxyl (–OH)
group on the second carbon. Compared to cellulose, this is a more digestible nutrient for
vertebrates, although only fish and some species of marine birds have a pancreatic chitinase
that breaks down chitin into N-acetyl-glucosamine.
Pancreatic Lipase: In vertebrates, pancreatic lipase is extremely important because it is the
principal enzyme that can digest fat. Pancreatic lipase hydrolyzes dietary triglycerides into
monoglycerides and free fatty acids, which are the absorbable units of fat. Like amylase,
lipase is secreted in its active form because there is no risk of pancreatic self-digestion by
lipase. When pancreatic enzymes are deficient, digestion of food is incomplete. Because the
pancreas is the only significant source of lipase, pancreatic enzyme deficiency results in
serious maldigestion of fats. The principal clinical manifestation of pancreatic exocrine
insufficiency in mammals is steatorrhea, or excessive undigested fat in the feces. Up to 60 to
70% of the ingested fat may be excreted in the feces. Digestion of protein and
carbohydrates is less impaired because salivary, gastric, and small-intestinal enzymes
contribute to the digestion of these two foodstuffs.
Pancreatic Aqueous Alkaline Secretion: Pancreatic enzymes function best in a neutral or
slightly alkaline environment, yet the highly acidic gastric contents are emptied into the
duodenal lumen in the vicinity of pancreatic enzyme entry into the duodenum. This acidic
chyme must be quickly neutralized in the duodenal lumen, not only to allow optimal
functioning of the pancreatic enzymes but also to prevent acid damage to the duodenal
mucosa. The alkaline (NaHCO3-rich) fluid secreted by the pancreas into the duodenal lumen
serves the important function of neutralizing the acidic chyme as it is emptied into the
duodenum from the stomach. This aqueous NaHCO3 secretion is by far the largest
component of pancreatic secretion. The volume of pancreatic secretion ranges between 1
and 2 liters per day in humans to as high as 12 liters per day in a pony, depending on the
types and degree of stimulation.
The liver
Besides pancreatic juice, the other secretory product that is emptied into the duodenal
lumen is bile. The biliary system includes the liver, the gallbladder, and associated ducts. Bile
is continuously secreted in ruminants, horses, and pigs, whereas in most animals that feed
at infrequent intervals, such as the dog and cat, bile is stored in the gallbladder until periods
of feeding and digestion.
Functions of the Liver
The liver is the largest and most important metabolic organ in the vertebrate body; it can be
viewed as the body’s major “biochemical factory.” The liver performs a wide variety of
functions, including the following:
• Secretion of bile salts for the digestive tract.
• Metabolic processing of the major categories of nutrients (carbohydrates, proteins, and
lipids) after their absorption from the digestive tract, including gluconeogenesis—the
process of converting noncarbohydrate nutrients into glucose.
• Detoxification or degradation of body wastes and hormones as well as drugs and other
foreign compounds.
• Synthesis of plasma (lipo)proteins, including those necessary for the clotting of blood, and
those that transport steroid and thyroid hormones, and phospholipids and cholesterol in the
blood.
• Storage of glycogen, fats, iron, copper, and many vitamins.
• Activation of vitamin D, which the liver accomplishes in conjunction with the kidneys.
• Removal of bacteria and worn-out red blood cells by Kupffer cells.
• Secretion of the hormones thrombopoietin (stimulates platelet production), hepcidin
(inhibits iron uptake from the intestine), insulin-like growth factor-I (stimulates growth), and
angiotensinogen (important in salt regulation).
• Excretion of cholesterol, biliverdin, and bilirubin, the latter two being breakdown products
derived from the destruction of worn-out red blood cells.
• Synthesis of ascorbic acid (vitamin C) in some species of mammals (excluding primates and
guinea pigs) and birds.
• Buoyancy in sharks because of high amounts of low density lipids.
Given this wide range of complex functions, there is little specialization of cells within the
liver. Each liver cell, or hepatocyte performs the same wide variety of metabolic and
secretory tasks. The specialization comes from the highly developed organelles within each
hepatocyte. The only liver function not accomplished by the hepatocytes is the phagocytic
activity carried out by Kupffer cells. In some species the liver performs additional functions
during particular stages of development. For example, the size of the liver is increased in
some animals engaged in reproduction. Synthesis of egg constituents (lipogenesis for yolk
and some albumin synthesis) is carried out in the avian liver. As a consequence, fatty livers
are a common problem in laying hens.
Gall Bladder
Bile is continuously secreted by the vertebrate liver and is diverted to the gallbladder
between meals. The opening of the bile duct into the duodenum is guarded by the sphincter
of Oddi, which prevents bile from entering the duodenum except during digestion of meals.
When this sphincter is closed, most of the bile secreted by the liver is diverted back up into
the gallbladder, a small, saclike structure tucked beneath the liver. Bile is subsequently
stored and concentrated in the gallbladder between meals. After a meal, bile enters the
duodenum as a result of the combined effects of gallbladder emptying and increased bile
secretion by the liver. Animals without a gallbladder include the rat, horse, pigeon, deer,
giraffe, elephant, and camel. Bile contains several organic constituents, namely bile salts,
cholesterol, lecithin, and bilirubin or biliverdin, all derived from hepatocyte activity. Even
though bile does not contain any digestive enzymes, it is important for the digestion and
absorption of fats. Bile salts are derivatives of cholesterol. To reduce their toxicity, mammals
conjugate bile acids with either taurine or glycine, whereas birds and fish form only the
taurine conjugate. Bile salts are actively secreted into the bile and eventually enter the
duodenum along with the other biliary constituents. Following their participation in fat
digestion and absorption, most bile salts are reabsorbed back into the blood by special
active-transport mechanisms located in the mammalian terminal ileum, the last portion of
the small intestine. (In birds, the majority of absorption takes place in the jejunum, the
second intestinal segment.) From here the bile salts are returned via the hepatic portal
system to the liver, which re-secretes them into the bile. This recycling of bile salts (and
some of the other biliary constituents) between the small intestine and liver is referred to as
the enterohepatic circulation (Figure 10). On average, bile salts cycle between the liver and
small intestine twice during the digestion of a typical meal. Approximately 5% of the
secreted bile salts ultimately escape into the feces daily. These lost bile salts are replaced by
new bile salts synthesized by the liver; thus, the size of the pool of bile salts is kept constant.
Bile salts aid fat digestion through their detergent action (emulsification) and facilitate fat
absorption through their participation in the formation of micelles.
Emulsification by Bile Salts: Emulsification refers to bile salts’ ability to convert large fat
globules into a lipid emulsion that consists of many small fat droplets suspended in the
aqueous chyme, thus increasing the surface area available for attack by pancreatic lipase.
Micellar Formation: Bile salts along with cholesterol and lecithin, which are also constituents
of bile play an important role in facilitating fat absorption through micellar formation. In a
micelle, the bile salts and lecithin aggregate in small clusters with their fat-soluble portions
huddled together in the middle to form a hydrophobic core, while their water-soluble
portions form an outer hydrophilic shell (Figure 11). Micelles are water soluble by virtue of
their hydrophilic shells, but they can dissolve water-insoluble (and hence lipid-soluble)
substances in their lipid-soluble cores. Micelles thus provide a handy vehicle for carrying
water-insoluble substances through the watery luminal contents. The most important lipid-
soluble substances thus carried are the products of fat digestion (monoglycerides and free
fatty acids) as well as fat-soluble vitamins, which are all transported to their sites of
absorption by means of the micelles. If they did not hitch a ride in the water-soluble
micelles, these nutrients would float on the surface of the aqueous chyme (just as oil floats
on top of water), never reaching the absorptive surfaces of the small intestine.
Small Intestine
The small intestine is a tube that lies coiled within the abdominal cavity, extending between
the stomach and the large intestine. It is somewhat arbitrarily divided into three segments
in most terrestrial vertebrates: the duodenum, the jejunum, and the ileum, In birds,
Meckel’s diverticulum, a vestige of the yolk sac, lies approximately midway along the small
intestine. The small intestine is the site at which most digestion and absorption of nutrients
takes place in vertebrates. An alternative strategy relies on the pregastric absorption of
some nutrients through the lining of the ruminoreticulum (see discussion of ruminants. In
addition, some animal groups can ferment cellulose postgastrically and absorb
nutrients through the lining of the colon and/or the cecum. A cross section of the small
intestine (Figure 12) reveals four major tissue layers. They are the mucosa, the submucosa,
the muscularis externa, and the serosa.
1. The mucosa lines the luminal surface of the digestive tract. It is divided into three layers:
a. A mucous membrane, an inner epithelial layer that serves as a protective surface as well
as being modified in particular areas for secretion and absorption. It contains exocrine cells
for secreting digestive juices, endocrine cells for secreting gastrointestinal hormones, and
epithelial cells specialized for absorbing digested nutrients.
b. The lamina propria, a thin middle layer of connective tissue on which the epithelium
rests. Small blood vessels, lymph vessels, and nerve fibers pass through the lamina propria,
and it houses the gut-associated lymphoid tissue (GALT), which is important in the defense
against intestinal bacteria.
c. The muscularis mucosa, a sparse outer layer of smooth muscle that lies adjacent to the
submucosa.
2. The submucosa is a thick layer of connective tissue that provides the digestive tract with
its distensibility and elasticity. It contains the larger blood and lymph vessels.
3. Surrounding the submucosa is the muscularis externa, the major smooth-muscle coat of
the digestive tube. The contractile activity of these smooth-muscle layers produces the
propulsive and mixing movements.
4. The serosa is the outer connective tissue covering of the digestive tract, which secretes a
serous fluid that lubricates and prevents friction between the digestive organs and
surrounding viscera. Throughout much of the tract, the serosa is continuous with the
mesentery, which suspends the digestive organs from the inner wall of the abdominal cavity
like a sling. This attachment provides relative fixation, supporting the digestive organs in
proper position, while still allowing them freedom for mixing and propulsive movements.
The mucous lining of the small intestine is remarkably well adapted to its special absorptive
function, for two reasons: (1) It has a very large surface area, and (2) the epithelial cells in
this lining have a variety of specialized transport mechanisms.
Adaptations that Increase the Small Intestine’s Surface Area
The following three modifications of the small-intestine mucosa greatly increase the surface
area available for absorption:
1. Folds: The inner surface of the small intestine is arranged in circular folds that are visible
to the naked eye and that increase the surface area threefold.
2. Villi: Projecting from this folded surface are microscopic, fingerlike projections known as
villi, which give the lining a velvety appearance and increase the surface area by another 10
times. Epithelial cells cover the surface of each villus.
3. Microvilli: Even smaller, hairlike projections known as microvilli arise from the luminal
surface of these epithelial cells, increasing the surface area another 20-fold in a formation
called the brush border. Each epithelial cell has as many as 3,000 to 6,000 of these microvilli,
which are visible only with an electron microscope.
Motility
Segmentation, the small intestine’s primary method of motility, both mixes and slowly
propels the chyme. Segmentation consists of ringlike contractions along the length of the
vertebrate small intestine. Within a matter of seconds, the contracted segments relax and
the previously relaxed areas contract. These oscillating contractions thoroughly mix the
chyme within the small-intestine lumen (Figure 13). This mixing serves the dual functions of
mixing the chyme with the digestive juices secreted into the small intestine lumen and
exposing all the chyme to the absorptive surfaces of the small intestine mucosa.
Secretion
Small-intestine secretions do not contain any digestive enzymes. Each day the exocrine
glands located in the small-intestine mucosa secrete into the lumen large volumes of an
aqueous salt and mucus solution known as the succus entericus (succus, “juice”; entericus,
“of the intestine”; about 1.5 liters in humans). However, no digestive enzymes are secreted
into this intestinal juice. The small intestine synthesizes digestive enzymes, but they function
within the borders of the epithelial cells that line the lumen instead of being secreted
directly into the lumen. As in other parts of the tract, mucus in the secretion provides
protection and lubrication. Furthermore, this aqueous secretion provides an abundance of
H2O to participate in the enzymatic digestion of food, which proceeds most efficiently when
all the reactants are in solution.
Digestion
Small-intestine enzymes complete the process of digestion at the brush border membrane.
Digestion within the small-intestine lumen is accomplished by the pancreatic enzymes, with
fat digestion being enhanced by bile secretion. As a result of those enzymes’ actions, fats
are completely reduced to their absorbable units of monoglycerides and free fatty acids,
proteins are broken down into small peptide fragments and some amino acids, and
carbohydrates are reduced to disaccharides and some monosaccharides. Thus, fat digestion
is completed within the small-intestine lumen, but carbohydrate and protein digestion have
not been brought to completion. The luminal surface of the mammalian small intestine
epithelial cells has a brush border. This contains different categories of enzymes:
1. Enterokinase, which activates the pancreatic enzyme trypsinogen.
2. The disaccharidases (maltase, sucrase, lactase, and trehalase), which complete
carbohydrate digestion by hydrolyzing the remaining disaccharides (maltose, sucrose,
lactose, and trehalose) into their constituent monosaccharides.
3. The aminopeptidases, which hydrolyze the small peptide fragments into their amino acid
components, thereby completing protein digestion. Thus, carbohydrate and protein
digestion are completed at the brush border. (Table 1). Not all vertebrate groups express
each of these enzymes in their brush border. For example, birds have no need of lactase but
do have an intestinal amylase. Because the microbes in the reticulorumen of a ruminant
scavenge most of the carbohydrates, the concentrations of disaccharidases in the small
intestine are low, with sucrase not synthesized at all. Vertebrates whose diet normally
contains chitin have evolved a chitinase enzyme. Bats, rodents, turtles, and insectivorous
lizards synthesize substantial quantities of chitinase in their gastric mucosa. Similarly, many
species of fish and birds produce chitinase in their pancreas, whereas other species rely on
intestinal bacteria to synthesize this enzyme.
Absorption
Most absorption occurs in the duodenum and jejunum; very little occurs in the ileum, not
because the ileum does not have absorptive capacity but because most absorption has
already been accomplished before the intestinal contents reach the ileum. The small
intestine has an abundant reserve absorptive capacity. Carbohydrate and protein are both
absorbed by secondary active transport and enter the blood. The absorption of fats is a
passive process because the lipid-soluble fatty end products merely dissolve in and pass
through the lipid portions of the membrane. Vitamin absorption is also largely passive.
Water-soluble vitamins (B complex vitamins and vitamin C) are primarily absorbed passively
with water, whereas fats soluble vitamins (vitamins A, D, E, and K) are carried in the micelles
and absorbed passively with the end products of fat digestion. Vitamin B12 is unique in that
it must be combined with gastric intrinsic factor from stomach parietal cells for absorption
by special transport in the terminal ileum.
Hindgut/Large Intestine
The hindgut of vertebrates consists of the colon, cecum, and rectum/cloaca (Figure 14);
however, in amphibians the hindgut is difficult to distinguish from the midgut, although the
diameter is somewhat larger. In most species a valve or sphincter separates the two
compartments. The small, fingerlike projection at the bottom of the cecum in humans and
some apes is the vermiform appendix, a lymphoid tissue that stores lymphocytes but that
has no direct digestive function. The colon, which makes up most of the mammalian large
intestine, varies considerably between animals in structure depending on diet. Generally,
the colon of mammals shows a remarkable range of structural variation and tends to be
proportionately longer than that of other vertebrates. In humans, there is a distinct
ascending colon, transverse colon, and descending colon. The ascending colon of ruminants,
pigs, and horses are dramatically modified in both size and structure. For example, in
ruminants and pigs it is much elongated and organized into coils. In the horse it is markedly
enlarged and occupies a considerable portion of the abdominal cavity. The transverse colon
is comparatively short, whereas the descending colon is continuous with the rectum (rectum
means “straight”). In amphibians, reptiles (including birds), and some mammals the hindgut
terminates, along with the renal and reproductive systems, in a cloaca, whereas in fish the
ducts from the urinary and genital tracts exit from the body separate from that of the
digestive tract.
The large intestine serves as a temporary storage site for excreta, functions in electrolyte
and fluid balance, and harbors microbes for fermentation and production of volatile fatty
acids The colon of a human normally receives about 500 mL of chyme from the small
intestine each day. Because most digestion and absorption have been accomplished in the
small intestine, the contents delivered to the colon consist of indigestible food residues
(such as cellulose), unabsorbed biliary components, and the remaining fluid. The colon
extracts more H2O and salt from the contents, so it is important in fluid-electrolyte balance.
What remains to be eliminated is known as excreta or feces. The primary function of the
large intestine is to store this fecal material before defecation. Cellulose and other
indigestible substances in the diet provide bulk and help maintain regular bowel movements
by contributing to the volume of the colonic contents. Symbiotic microbes live in the cecum
and colon in most if not all species, where they synthesize some vitamins such as vitamin K.
Microbes also make volatile fatty acids (VFAs; fatty acids with 6 or fewer carbons).
Diet composition governs variation in structure of the large intestine e.g. Carnivores (such as
cats and dogs) tend to have the simplest digestive tracts, with comparatively short,
unstructured colons. Thus, in carnivores, the major function of the colon is the absorption of
electrolytes, water, and other materials that escaped absorption in the small intestine. In
omnivores and particularly in herbivores that ingest considerable amounts of complex
polysaccharides, notably rabbits and horses, the structure of the large intestine tends to be
more complex. Generally, the ceca and/or the colon are sacculated (having expandable side
sacs) and voluminous, providing a site for microbial digestion.
Mobility
Most of the time, movements of the large intestine are slow and non-propulsive, as is
appropriate for its absorptive and storage functions. The colon’s primary method of motility
are haustral contractions initiated by the autonomous rhythmicity of colonic smooth muscle
cells. These movements slowly shuffle the contents in a back-and-forth mixing movement
that exposes the colonic contents to the absorptive mucosa. By prolonging the retention of
the colonic contents, more time is made available for microbial digestion. This is particularly
important in the pig and horse because they lack a rumen in which to digest dietary
cellulose.
Generally after meals, a marked increase in motility takes place during which large segments
of the colon contract simultaneously, driving the feces one third to three fourths of the
length of the colon in a few seconds. These massive contractions, appropriately called mass
movements, drive the colonic contents into the distal portion of the large intestine, where
material is stored until defecation occurs. Feces are eliminated by the defecation reflex.
When mass movements of the colon move fecal material into the rectum, the resultant
distension of the rectum stimulates stretch receptors in the rectal wall, thus initiating the
defecation reflex. This reflex causes the internal anal sphincter (which consists of smooth
muscle) to relax and the rectum and sigmoid colon to contract more vigorously. If the
external anal sphincter (which consists of skeletal muscle) is also relaxed, defecation occurs.
Being skeletal muscle, the external anal sphincter is under voluntary control. The initial
distension of the rectal wall is accompanied by the conscious urge to defecate. If
circumstances are unfavorable for defecation, voluntary tightening of the external anal
sphincter can prevent defecation despite the defecation reflex. If defecation is delayed, the
distended rectal wall gradually relaxes, and the urge to defecate subsides until the next
mass movement propels more feces into the rectum, once again distending the rectum and
triggering the defecation reflex. During periods of inactivity, both anal sphincters remain
contracted to ensure fecal continence. When defecation does occur, voluntary straining
movements that involve simultaneous contraction of the abdominal muscles and a forcible
expiration against a closed glottis usually assist it. This maneuver brings about a large
increase in intra-abdominal pressure, which helps eliminate the feces. Defecation is also a
normal response to fear, presumably in response to activation of neural centers in the brain.
Secretion
Large-intestine secretion is protective in nature. The large intestine does not secrete any
digestive enzymes. Colonic buffers consist of an alkaline (HCO3− and PO43−) mucous
solution, whose function is to protect the large intestine mucosa from mechanical and
chemical injury. The mucus provides lubrication to facilitate passage of the feces, whereas
the buffers neutralize acids produced by local bacterial fermentation. The large intestine
converts the luminal contents into feces. Fecal material normally consists of undigested
cellulose and other unabsorbed food residues, bilirubin (or biliverdin), small amounts of salt
and water, and bacteria.
Absorption
Some absorption takes place within the vertebrate colon, but not to the same extent as in
the small intestine. Because the luminal surface of the colon is fairly smooth, it has
considerably less absorptive surface area than the small intestine. In many vertebrates,
specialized transport mechanisms are not present in the colonic mucosa for absorption of
glucose or amino acids, as there are in the small intestine. A notable exception is the colon
of birds, where both glucose and amino acids are absorbed by secondary active transport.
Thus, the glucose and amino acids not reabsorbed in the kidney can either be reabsorbed
into the blood or used by the microorganisms in the ceca. When excessive small-intestine
motility delivers the contents to the colon before absorption of nutrients has been
completed, the colon cannot absorb these materials, and they are lost in diarrhea.
Ruminant Digestion
Ruminants are a group of animals that have achieved the highest degree of specialization in
fermenting plant material. Animals having a rumen can exploit the vast supplies of structural
carbohydrates found in the plant cell wall and convert them into a source of nutrients.
Ruminants, so named because they ruminate (chew the cud), also voluntarily regurgitate
partially digested food back into the mouth to complete the mechanical grinding of the
ingested plant material. This has often been thought of as an evolutionary development that
has allowed ruminants (often prey animals) to consume feed in haste and later mechanically
process their food during leisure times of safety. Ruminant species have evolved a stomach
of sufficient size and motility to house a population of microbes able to break down
cellulose and other complex polysaccharides into end products of fermentation, which meet
the nutritional requirements of the host animal.
The rumen is divided into separate compartments. The stomach of true ruminants
(Ruminantia), which includes cattle, sheep, goats, deer, giraffe, and antelope, is divided into
four compartments, which occupy approximately three quarters of the abdominal cavity.
The forestomach (the pregastric region) consists of three chambers: the rumen, reticulum,
and omasum, each of which is involved in the storage and passage of ingested food (Figure
15). Pseudoruminants (Tylpoda), including llamas and camels, have a three-compartment
stomach, the omasum being absent. The rumen and its continuation, the reticulum, also
have an important role in the absorption of nutrients and simple molecules. It is in these
two compartments that the bulk of anaerobic fermentation of plant material occurs and
cellulose is catabolized into digestible units. In all ruminant animals, the rumen is the most
spacious structure, followed by the abomasum. In a majority of ruminant species, the
reticulum is greater in size than the omasum, which is the smallest of the four
compartments. The variability in size of the latter two compartments is ultimately
determined by the feeding strategies of the particular animal group as well as by seasonal
changes in food availability. Surrounding the ruminant stomach is an outer muscular layer,
which consists of a thin sheet of longitudinally directed smooth muscle, whereas the inner
layer is thick and circular in structure. The muscular layers mix the ingesta and provide for
the progressive movement of this material through the stomach toward the small intestine.
Rumen mixing also promotes the turnover of indigestible particles that would quickly clog
the rumen if allowed to accumulate. The ruminal cavity is divided into internal
compartments by the presence of pillars. Longitudinal pillars partially divide the rumen into
dorsal and ventral sacs. When contracted, these muscular folds enable the mixing and
movement of large volumes of fluid. These pillars also help stabilize the fluid contents of the
ruminoreticulum and limit the movement of the digesta toward the reticulum. Lining the
rumen are fingerlike projections, the papillae, that increase the surface area available for
absorption of nutrients. Feeding high-concentrate diets (replacing the roughage component
of the diet with higher-energy grains) to cattle results in the gradual degradation of these
structures. Starvation also decreases the size of the papillae. The ruminal compartment is
separated from the reticulum by the ruminoreticular fold. However, the separation does not
inhibit the free exchange of digesta between the two compartments. Within these two sacs
occurs most fermentation and absorption of nutrients. Hardware and other foreign objects
accumulate in the reticulum because of its position relative to the esophagus. Hardware
disease occurs in ruminants when a foreign object, usually a piece of metal that has been
swallowed, penetrates the reticulum. The condition is particularly common in cattle because
they do not separate foreign objects—nails, wire, and so forth—from feed, and swallow
everything before it is completely chewed. Penetration of the reticulum wall permits
bacteria and partially digested food to spill out into the abdominal cavity, resulting in
peritonitis. The esophagus terminates at the junction between the reticulum and the rumen,
the cardia, and opens directly over the cavity of the reticulum. It is encircled by strands of
smooth muscle that are organized to form a reticular groove. The reticular grove extends
from the opening of the esophagus to the reticulo-omasal orifice. The luminal surface of the
reticulum is lined with ridges, which are thought to be involved in the sorting of particles
that pass near the reticulo-omasal orifice. Ingesta ultimately entering the omasum are
identical in consistency to that found in the ruminoreticulum. The omasum provides a
channel for the passage of ingesta from the reticulum into the glandular stomach, the
abomasum. The luminal surface is characterized by the presence of leaflike structures that
absorb water and nutrients as well as limit the passage of large particles. At the junction
with the abomasum is the omasoabomasal orifice, a well-developed structure that lacks a
sphincter to limit backflow. It also regulates the movement of materials from the omasum
into the abomasum during digestion and inhibits the movement of ingesta from the
omasum when the abomasum is full. The acid-secreting region of the stomach, the
abomasum, functions in the digestion of protein and lysis of rumen microbes. It is
structurally similar to that of stomachs of nonruminants except for the presence of relatively
large spiral folds. It has a much larger fundic area and a larger pyloric region at the junction
of the abomasum and small intestine. In ruminants that are fed coarse plant material,
gastric juice secretion is continuous, whereas it is cyclic in animals provided concentrate
diets at intervals during the day.
Rumination is the regurgitation, remastication, and reswallowing of ingesta. Rumination
cycles (or “cud chewing”) are closely linked with ruminoreticular motility and last
approximately a minute. The influx of digesta into the esophagus occurs simultaneously
with the opening of the lower esophageal sphincter and a relaxing of the upper esophageal
sphincter. The semiliquid digesta is propelled up the esophagus by reverse peristalsis. Once
food enters the mouth the liquid portion is immediately reswallowed, but the particulate
material remains in the mouth for maceration by the teeth and reinsalivation, mainly from
the parotid gland on the side of chewing. Each rumination cycle is divided into a prolonged
chewing phase followed by a short redeglutition phase. The food bolus is reformed and
reswallowed. The amount of time spent ruminating depends on the species of animal as
well as the composition of the food. In general, the greater the roughage content of the
diet, the more time that is spent ruminating the digesta. Forages and hay require more
chewing than do feed concentrates. The environment of the rumen fosters the growth of
anaerobic microbes. Microorganisms contained in the rumen break down cellulose into
short-chain fatty acids that are absorbed through the rumen wall. Most of these
microorganisms are attached to partially digested feed particles (approximately 75%),
whereas the remaining either adhere to the rumen wall or are present in the rumen fluid.
The rumen is normally well buffered by the copious f ow of saliva (which contains both
bicarbonates and phosphates), production of short-chain organic acids, as well as the
buffering capacity of the animal’s diet. The microbial populations found in the rumen
include anaerobic species of bacteria, archaea, protozoa, and fungi. Of these, bacteria are
the greatest in number and diversity of species.
Fermentation is the most important process to occur in the rumen. It is also the first step in
the generation of nutrients suitable for the host ruminant. Because the diet of ruminant
animals contains varying proportions of insoluble celluloses, hemicelluloses (structural
component of plant cells), pectins (polysaccharide isolated from fruits), and starch
(polysaccharide that stores energy in plants), these complex polysaccharides need to be
converted into simpler forms to be metabolized by the ruminant microbes. Most bacteria
attach to feed particles and digest the structurally complex polysaccharides via cellulase
enzyme complexes tightly bound to the surface of the bacteria. Similar cellulase complexes
are used by protozoa to digest engulfed feed particles, whereas fungi can digest
polysaccharides by bound enzymes or by releasing the cellulases into the surrounding fluid.
Starch and cellulose are degraded into glucose, whereas hemicellulose and pectin are
converted into xylose (monosaccharide). Sugars and pectins are the most rapidly fermented,
followed by starches and fiber. Most simple sugars do not accumulate in the rumen liquor,
because they are taken up and metabolized by the microbes populating the forestomach,
regardless of whether they participated in the initial hydrolysis of the complex
polysaccharides. However, depending on the rate and extent of digestion, some
carbohydrates escape the rumen. For example, most fiber, considerable starch, and some
simple sugars escape the rumen environment.
Each of the microbial populations in the rumen can hydrolyze protein into constituent
polypeptides and amino acids and use these products as a source of nitrogen for their own
growth. Polypeptides up to six amino acids long can be absorbed by the rumen bacteria and
further hydrolyzed to end products such as amino acids, or are deaminated (the nitrogenous
amine group is removed) to produce ammonia. Ammonia as well as amino acids are readily
absorbed through the lining of the ruminoreticulum and omasum.
Check your understanding
1. Describe the different modes of animal feeding. Describe the four basic digestive
processes.
2. List the three categories of energy-rich foodstuffs and the absorbable units of each.
3. List the common components of a representative digestive system, and describe its
cross-sectional anatomy.
4. Discuss the key features of mastication. What is the role of saliva in digestion?
5. Describe how swallowing works.
6. Describe the functions of the esophagus and its modified section, the crop.
7. Describe the three phases of gastric secretion and the factors that affect each.
8. What enzyme is produced in the stomach, and how is it activated?
9. What are the functions of the proventriculus and gizzard?
10. What are the contributions of the accessory digestive organs in vertebrates?
 11. What are the nondigestive functions of the liver?
12. What is the principal function of bile salts?
13. Describe how the three major categories of nutrients are digested in the small
intestine.
14. What are the principal functions of the large intestine?
15. Describe the types of motility in each component of the digestive tract. What factors
control each type of motility? State the composition of the digestive juice secreted by
each component of the digestive system.
16. Describe the factors that control each digestive secretion.
17. List the enzymes involved in digesting each category of foodstuff. Indicate the source
and control of secretion of each of the enzymes.
18. Describe the process of mucosal turnover in the stomach and small intestine.
19. Why are some digestive enzymes secreted in inactive form? How are they activated?
20. What absorption processes take place within each component of the digestive tract?
What special adaptations of the small intestine enhance its absorptive capacity?
21. Describe the absorptive mechanisms for salt, water, carbohydrate, protein, and fat.
RESPIRATORY SYSTEMS
Gas Demands: General Problems and Evolutionary Solutions
Energy is essential for sustaining all life supporting cellular activities. For most animals to
survive for extended periods of time, aerobic (oxygen-using) metabolism is necessary. In
addition to obtaining O2, animals must eliminate the CO2 produced as a byproduct of
aerobic metabolism at the same rate it is produced to prevent dangerous fluctuations in pH
because CO2 generates carbonic acid. The term respiration refers to all of the processes of
gas movement and metabolism, with two distinct components:
• The term internal or cellular respiration refers to the intracellular metabolic processes
carried out within the mitochondria, which use O2 and produce CO2 during the derivation
of energy from nutrient molecules.
• The term external respiration refers to the sequence of events involved in the exchange of
O2 and CO2 between the external environment and cellular mitochondria. External, not
cellular, respiration is the focus of this topic.
Overview of External Respiration
External Respiration involves up to four major steps of transport and exchange. For the
most part, gases in the external respiration sequence move by two methods:
1. Exchange (i.e., O2 and CO2 moving oppositely) across membranes by the relatively slow
process of diffusion, and
2. Bulk transport—the movement of the medium that contains the O2 and CO2 (circulation):
a. bypasses diffusion altogether to move gases much more quickly than diffusion; and b.
enhances diffusion gradients. These two processes can occur in up to four steps,
summarized in Figure1:
Step 1. Ventilation: bulk transport of external media across a gas exchange surface. This
motion, called ventilation, arises from environmental movements (e.g., winds or currents),
an animal’s locomotion, and/or breathing if it is actively and specifically produced.
Step 2. Respiratory exchange: gas diffusion between the environmental medium and
internal body fluids. This occurs at a respiratory surface, which may be a dedicated organ
such as a lung or gill, and the internal fluid may be the extracellular fluid (ECF) in a
circulatory system.
Step 3. Circulation: bulk transport of the ECF.
Step 4. Cellular exchange: gas diffusion between the outside (typically in the ECF, but
sometimes the external environment) and the ICF. This is the ultimate goal of external
respiration: exchange of gases between the cell’s immediate surroundings and its
mitochondria. All animals have gas exchange with their cells (step 4) but not necessarily all
other steps; for example, vertebrates have all four steps, but insects have steps 1, 2, and 4.
When we refer to an animal’s respiratory system, we are not talking about all these steps of
external respiration, rather only steps 1 and 2.
Water Respirers
Water is a more difficult medium than air for gas exchange. Though life began in water, it
contains much less O2 than air (Table 11-1). It is also problematic for gas exchange in other
ways. A comparison of air and water reveals the following points:
1. Viscosity: Water has a higher viscosity than air that necessitates a higher energy output to
maintain flow over the respiratory surface. The higher density of water also entails a higher
cost of acceleration.
2. Solubility: CO2 is and its product, bicarbonate, being polar, are in much higher
concentrations than in air. However, O2 concentration of water is considerably smaller than
in the gas phase: 1 L of water at 15˚C contains 7 mL of O2, whereas 1 L of air contains 209
mL of O2. For this reason, approximately 30 times more water than air must be moved to
achieve the same ventilatory transport of O2.
3. Diffusion: The rate of diffusion of gases in water is about 10,000-fold slower than in air.
4. Salinity: The solubility of O2 and CO2 decrease with increases in salinity; no comparable
effect occurs in air.
5. Temperature: Diffusion rates for gases increase with temperature in both air and water;
however, solubility of O2 and CO2 are decreased as ambient temperature increases. These
changes in solubility are critical; as temperature is raised from 0 to 35˚C, O2 concentration is
reduced by 50%. Because an increase in temperature raises the metabolic rate in
ectotherms (animals whose body temperatures depend on the environment), the associated
reduction in O2 solubility in water exerts an ecological pressure for aquatic species to obtain
access to air. 6. Habitat variation: The O2 content of water is subject to greater variation
than that of air.
7. Composition: Unlike air, water can contain many life sustaining components other than
gases. These include dissolved ions and organic matter.
The limitations of diffusion in water are overcome with gills and other external thin, high
surface-area structures, internal circulation, and flow-through breathing.
1. Integument: Integumentary respiration is important in virtually all amphibians and
aquatic reptiles and in most fishes. During hibernation, for example, frogs and turtles
exchange all their respiratory gases through this route while submerged in ponds or
buried beneath the bank of a stream. Eels normally exchange 60% of their CO2 and O2
through their highly vascular skins. Of particular note are the lungless salamanders of the
family Plethodontidae. Because the skin of these animals is also important for protection
against the environment, the efficiency of gas exchange is compromised.
2. Gills: Non-integumentary structures for gas exchange evolved in most water
breathers with larger and/or less-thin bodies and higher metabolisms. Most of these
specialized respiratory organs are called gills (Figure 2), evaginations of tissue protruding
into the external medium. Gills range from simple integumentary bulges, to branched
filaments, to stacks of lamellae (flat platelets on filaments). Filaments and lamellae
greatly increase surface area. The gill system of fish consists of gill arches, the tissue that
provides skeletal support for a double series of gill filaments, each of which carries a row
of lamellae on either side. Normally there are five separate pairs of these arches, covered
with a protective bony plate called the operculum, which opens on one side to the
outside world. The basic unit of gas exchange in the gill is the lamella, not the arch or
filament.
Gas exchange in the most active aquatic species requires the aid of a dedicated muscle-
driven form of breathing. In fishes (Figure 3). Water is pumped over the gills of bony fish by
skeletal muscle pumps in the buccal (mouth) and opercular cavities. Ventilation of the gills
operates by a cycle of negative and positive pressure gradients. As the mouth opens, the
opercula are shut, which leads to a negative pressure gradient in the buccal and opercular
cavities, resulting in the inward movement of O2-rich water. The mouth is then closed and
the opercular cavity constricts, forcing water through the gills. At this point the water that is
trapped in the gills is under higher pressure than outside. When the opercula open, the
positive pressure gradient forces water outward across the gills and through the opercular
exit.
Another way gas exchange is maximized is through the arrangement of blood flow. To be
able to extract the maximum amount of O2 from the water flowing through the gills, blood
flows in a direction opposite or countercurrent to that of water flow that is, blood flow
through the capillaries is opposite to the stream of water flowing through the gill lamellae,
such that blood
moving through the lamellae continually encounters water whose O2 content is higher than
what is present in the capillary. Thus, keeping gases diffusing into the blood. This anatomical
arrangement permits the O2 content of arterial blood to exceed that in the respired water.
Air Respirers
The evolutionary transition to land involved new challenges for external respiration. Firstly,
air is much less viscous than water and it contains much more O2 than any body of water.
Secondly, because respiratory surfaces are typically thin for diffusion, they can potentially
collapse in air under gravity and, more importantly, dry out rapidly if exposed to air.
Therefore, in air respirers, the respiratory surfaces must be kept moist to maintain the
integrity of the respiratory surface. There are two broad ways to do so:
• Remain in moist conditions. Such land animals closely resemble small aquatic animals in
respiratory features; for example, many rely on integumentary exchange. But because air
with its high O2 content is close at hand, this type of exchange can work well in larger
animals. • Have covered or fully internal structures for gas exchange, with secretions to
moisten the surface. Structures include internal air tubes called tracheae (insects), gilllike
book lungs (scorpions and some spiders), mantle cavities ( snails), or vascularized sacs called
lungs, which provide air for internal circulation (land vertebrates, including penguins and
whales that have re-evolved into aquatic habitats). Some of these form as invaginations
rather than the evaginations; others form as evaginations off of digestive tracts, but are fully
internal.
The respiratory system of vertebrate lung breathers includes the respiratory structures
leading into the lungs, the lungs themselves, and the structures of the thorax (chest)
involved in moving air through the airways into and out of the lungs. The respiratory airways
are tubes that carry air between the atmosphere and the lung surfaces such as alveoli. In
some cases, these airways can also function in gas exchange.
Evolution of Airways and Lungs
The first air-breathing vertebrates were bimodal. Vertebrate air breathing is believed to
have been favored among those animals living in habitats similar to modern tropical
lowlands, where warm water and seasonal drought results in stagnation of ponds leading to
aquatic hypoxia (low oxygen), and even desiccation.
Fishes
The first evolutionary transition from aquatic to terrestrial life produced distinct fishes with
a unique set of adaptations to respiring in both media. Some had modified gills (such as air-
breathing catfish, with more arch support to prevent gill collapse), but others were bimodal
breathers with, in addition to gills in water, the ability to breathe air by integumentary
exchange (such as some eels), parts of the digestive system including oral or stomach
linings, or separate air sacs called lungs. Bimodal breathing is used by some fishes in waters
that become anoxic (such as stagnant swamps) or in ponds that dry out seasonally. In
addition, some have gills, lungs, and some integumentary (skin) gas exchange with the result
that they are actually trimodal breathers (such as the reedfish, Calamoichthys calabaricus).
The most successful vertebrate groups in terms of terrestrial adaptation are those that
evolved true lungs. Lungs in fishes originally evolved as a simple ventral (internal)
evagination of the pharynx, and in some groups evolved into a dorsal gas bladder (see p.
539 and Figure 11-32). Eventually the gas bladder transformed into a structure specialized
for both sound reception and buoyancy control and in many cases lost its respiratory
function. In at least one group of fishes, however, the air sac became paired and ventrally
oriented, leading eventually to the lungs of terrestrial amphibians, reptiles, birds, and
mammals. The tube connecting the pharynx to the lungs became the trachea (windpipe),
splitting into two primary bronchi for the paired lungs (the anatomy found in most
terrestrial vertebrates).
Amphibians
Amphibians, the first class of vertebrates to evolve from lung-bearing fishes, are noted for
their bimodal lifestyles, living both in the water and air. Aquatic and terrestrial amphibians
rely to varying degrees on integuments, gills, and lungs for gas exchange. For example, some
species of salamanders are without lungs and are solely dependent on cutaneous gas
exchange. In these animals the skin is moist and well vascularized. At the other extreme,
one salamander (Siren lacertina) has trimodal breathing. In frogs, most larval stages have
gills, whereas most adults have lungs that are comparatively simple and non-
compartmentalized (Figure 3). Air enters these lungs from the pharynx via the trachea and
bronchi; note that the pharynx also branches into the esophagus, the tube through which
food passes to the stomach, reflecting the way that lungs first evolved. In larger species
needing greater surface area because of scaling problems, the lung is folded into alveoli.
However, alveoli are larger and less numerous than in vertebrates with higher metabolisms.
Air is forced by positive pressure into their lungs by a buccal pump (originating in the
mouth) that is similar in function to that used in fish. Normally, several inspiratory
oscillations are required to completely fill the lungs, whereas one long exhalation empties
the lungs. These animals are bimodal skin-lung breathers (Figure 4), but O2 uptake is
primarily through the lung, whereas CO2 elimination is almost exclusively cutaneous. In the
ancestors of the first exclusively air breathers, water pumping was completely abandoned
with the buccal muscles exclusively functioning as a positive-pressure air pump to inflate the
lungs. As the dependence on branchial O2 uptake decreased, the gills and branchial arteries
became reduced and internalized. The diffuse, externally oriented chemoreceptors for
monitoring gas concentrations located in the gills evolved into discrete arterial
chemoreceptors located near the carotid artery and in the aortic arch (see the section on
breathing regulation later. Adaptations to air breathing also included a decrease in the
affinity of hemoglobin for O2 that reflected the much greater O2 availability in air.
Reptiles
Compartmentalized lungs are an important adaptation in some reptiles as well as birds and
mammals, but what separates these groups from all others is their mechanism of
ventilation. Instead of forcing air from the buccal cavity into the lungs (amphibians and
some reptiles), air flows into the lungs because of a negative pressure.
Reptile lungs are expandable tidally ventilated sacs, which may be simple or with several
large sacs and even some alveoli (Figure 5). The simplest reptilian lung is comparable to a
single, oversized alveolus. Vascularized ingrowths, or septae (dividing walls or partitions),
penetrate centrally from the lung’s perimeter and subdivide the pulmonary lumen into a
series of spatial units called ediculae (if they are as wide as they are deep, as in tortoises,
chameleons, and geckos) or faveoli (if they are deeper than they are wide, as in snakes and
iguanids). Gas exchange occurs principally on the septae, although they are poorly
vascularized compared to alveoli. Unlike mammalian alveoli, ediculae are relatively passive
participants during ventilation and do not contribute to the movement of air during
inhalation and exhalation. Airflow during ventilation is tidal and bellows-like. Lizards and
snakes rely solely on costal (rib muscle) ventilation resulting from simple rib-cage expansion
to create negative pressure for inhalation, and contraction for exhalation.
Birds and Mammals
To meet the energy demands of birds and mammals with their increased metabolic rates,
the surface area of the lung available for gas exchange had to markedly increase. The
mammalian solution was the elaboration of numerous very small alveoli (Figures 6),
whereas the avian respiratory system, which is the most complex of the vertebrates,
evolved parabronchi with air capillaries. The cardiovascular system became increasingly
modified to perfuse the gas exchange organ. Oxygenated blood from the lung achieved
complete separation from systemic venous blood with a four-chambered heart. Most
mammals are bimodal due to integumentary gas exchange, as exemplified by bats: in flight
they are capable of eliminating almost 12% of their CO2 across the surface of their wings.
Approximately 1 to 2% of the total CO2 and O2 in many other mammals can be exchanged
directly through the skin.
Mammalian Respiratory Structure
Mammalian airways begin with the nasal passages (in a nose or blowhole) (Figure 7). The
nasal passages open into the pharynx (throat), which serves as a common passageway for
both the respiratory and digestive systems. Because the pharynx serves as a common
passageway for food and air, reflex mechanisms exist to close off the trachea during
swallowing so that food enters the esophagus and not the airways. The esophagus remains
closed except during swallowing to prevent air from entering the stomach during breathing.
The trachea is lined with two kinds of cells: mucus-secreting cells, which lubricate it, and
ciliated cells lined with tiny hairs that continually beat upward, pushing impurities such as
inhaled particles and dust, up and out of the trachea. Again, the trachea divides into right
and left bronchi, each entering one lung. Within each lung, the bronchus continues to
branch into progressively narrower, shorter, and more numerous airways called
bronchioles, much like the branching of a tree. Clustered at the ends of the terminal
bronchioles in mammals are the alveoli. To permit airflow in and out of the gas-exchanging
portions of the lungs, the continuum of conducting airways, from the entrance through the
terminal bronchioles to the alveoli, must remain open most or all of the time. The trachea
and larger bronchi in most mammals are fairly rigid, non-muscular tubes encircled by a
series of cartilaginous rings that prevent the tubes’ compression. The smaller bronchioles
have no cartilage to hold them open. Their walls contain smooth muscle that is innervated
by the autonomic nervous system and is sensitive to certain hormones and local chemicals.
These factors, by varying the degree of contraction of bronchiolar smooth muscle and hence
the caliber of these small terminal airways, are able to regulate the amount of air passing
between the atmosphere and each cluster of alveoli.
Mammalian lungs occupy most of the volume of the thoracic (chest) cavity, the only other
structures in the chest being the heart and associated vessels, the esophagus, the thymus,
and some nerves. Separating each lung from the thoracic wall and other surrounding
structures is a double-walled, closed sac called the pleural sac (Figure 8). The interior of the
pleural sac is known as the pleural cavity. The surfaces of the pleura secrete a thin
intrapleural fluid, which lubricates the pleural surfaces as they slide past each other during
respiratory movements. The pleural cavity plays a crucial role in the flow of air.
Respiration in Mammals
The following changes occur in a mammal during one respiratory cycle—that is, one breath
in (inspiration) and out (expiration).
Inspiration
Contraction of Inspiratory Muscles: Before the beginning of inspiration, the respiratory
muscles are relaxed (Figure 8), no air is flowing, and intra-alveolar pressure (pressure inside
the alveoli) is equal to atmospheric pressure. At the onset of inspiration, these muscles are
stimulated to contract, resulting in enlargement of the thoracic cavity. The major inspiratory
muscles are the diaphragm and external intercostal muscles.
1. The relaxed diaphragm assumes a dome shape that protrudes into the thoracic cavity.
When the diaphragm contracts on stimulation by the phrenic nerve, it contracts downward,
thereby enlarging the volume of the thoracic cavity.
2. Whereas contraction of the diaphragm enlarges the thoracic cavity in the vertical
dimension, contraction of the external intercostal muscles, whose fibers run downward and
forward between adjacent ribs, enlarges the thoracic cavity in both the lateral (side-to-side)
and anteroposterior (front-to-back) dimensions. They do so by expanding the ribs and
subsequently the sternum outward.
Exhalation
Elastic Recoil and Relaxation of Inspiratory Muscles: At the end of inspiration, the
inspiratory muscles relax. The diaphragm rebounds to its original dome-shaped position as it
relaxes; the expanded rib cage contracts when the external intercostals relax; and the chest
wall and stretched lungs recoil to their pre-inspiratory size because of their elastic
properties. As the lungs become smaller in volume, the intra-alveolar pressure rises because
the greater number of air molecules contained within the larger lung volume at the end of
inspiration are now compressed into a smaller volume. Air now leaves the lungs down its
pressure gradient. Outward flow of air ceases when intra-alveolar pressure becomes equal
to atmospheric pressure.
Contraction of Expiratory Muscles: In most mammals, the inspiratory and expiratory phases
are cyclical and smooth. Expiration in humans is normally a passive process during quiet
breathing because it is accomplished by elastic recoil of the lungs on relaxation of the
inspiratory muscles, with no muscular exertion or energy expenditure required. In contrast,
inspiration is active because it is brought about by contraction of inspiratory muscles at the
expense of energy use. To empty the lungs more completely and more rapidly than is
accomplished during quiet breathing, as during the deeper breaths accompanying
locomotory activity, expiration does become active in mammals. The intra-alveolar pressure
must be increased even further above atmospheric pressure than can be accomplished by
simple relaxation of the inspiratory muscles and elastic recoil of the lungs. To produce such
a forced, or active expiration, two sets of expiratory muscles must contract to further
reduce the volume of the thoracic cavity and lungs:
1. The most important expiratory muscles are the abdominal wall muscles. As the
abdominal muscles contract, the resultant increase in intra-abdominal pressure exerts a
force on the diaphragm, pushing it further into the thoracic cavity than in its relaxed
position, thus decreasing the vertical dimension of the thoracic cavity even more.
2. The other expiratory muscles are the internal intercostal muscles, whose contraction
pulls the ribs inward, flattening the chest wall and further decreasing the size of the thoracic
cavity; this action is antagonistic to that of the external intercostal muscles. These muscles
increase the differential between intra-alveolar and atmospheric pressure above that of
passive expiration, so more air leaves down the pressure gradient before equilibration is
achieved. In this way, the lungs are emptied more completely during forceful, active
expiration than during quiet, passive expiration.
Bird’s Respiratory Structure
A greater efficiency is achieved in birds compared to mammals due to a complete
separation of ventilation and gas-exchange functions. In contrast to those of mammals, the
lungs of birds only perform gas exchange and are comparatively small and inelastic (and
thus do not change in volume during the respiratory cycle). Instead, ventilation arises from
expandable air sacs (Figure 10) that perform a bellows-like tidal function comparable to the
mammalian lung but without gas exchange. As you will see, this separation of function
allows tidal flow to be converted into a flow-through pattern in the lungs, which results in
an increase in exchange efficiency. Again, air enters the nasal passages, the trachea, and
bronchi. The tracheal volume of a bird is considerably larger than that of a comparably sized
mammal. Within each lung a bronchus gives rise to several sets of secondary bronchi,
named according to the regions of the lung that they supply. The most important groups
include the ventrobronchi and the dorsobronchi. As in alligators, the secondary bronchi are
connected to each other by a number of parabronchi from which the air capillaries (gas
exchange surface) originate. Parabronchi are cylindrical and run in parallel with each other.
Together, the secondary bronchi and their interconnecting parabronchi form an integrated
unit that enables flow through air movement. Airflow is from the dorsobronchi, through the
parabronchi and air capillaries, to the ventrobronchi. In birds, air is not diluted with “old” air
as in mammalian alveoli.
Air Sacs
In most birds, the air sacs arise in the embryo from six primordial pairs of sacs, two of which
fuse at the time around hatch. Thus, there are eight air sacs in the adult domestic fowl: one
cervical and one clavicular sac, two cranial thoracic and two caudal thoracic sacs in addition
to the two abdominal sacs. Functionally, there are two groups of air sacs, an anterior (or
cranial) group and a posterior (or caudal) group. The anterior group consists of several
smaller sacs that connect with the ventrobronchi and receive expelled air from the lungs,
whereas the posterior group, which includes the comparatively large abdominal sacs,
connects to the caudal end of the main bronchus and receives relatively fresh air from the
trachea. Because the blood supply to the air sacs is essentially negligible, no gas exchange
occurs across this surface. Air sacs are held open by their attachment to the structures that
surround them and occasionally even penetrate the medullary (inner portion) cavities of
some bones.
Respiration in Birds
Flow-through breathing plus crosscurrent blood flow enhances gas exchange in birds. First,
the sacs must inflate and deflate tidally, much like mammalian lungs. Birds do not have a
muscular diaphragm but instead have a membranous diaphragm that is attached to the
body wall by muscles. Birds rely primarily on a highly modified costal (rib) movement in
association with a well-developed sternum (the long, flat breastbone) to power air-sac
ventilation. In addition, in some species of birds the joints of the ribs permit fore–aft
movement of the rib cage during ventilation. As a result, avian ribs rotate such that the
posterior end of the sternum is depressed on inhalation and generates negative intra-
abdominal pressures that helps fill the comparatively large abdominal air sacs. Although
they do not need to be as efficient as fishes because air is a much better medium for oxygen
uptake, birds do require greater efficiency than mammals because of their higher
metabolisms. This occurs at three levels:
1. Narrower diffusion distance between air and blood capillaries.
2. Flow-through movement in the parabronchi and air capillaries. To comprehend this
process, we follow the passage of an inert component such as N2 through the avian
respiratory system (Figure 11). The inhaled N2 gas is initially mixed with gases present in the
dead air space of the trachea and primary bronchus of each lung. Then the posterior air sacs
inflate for the first inspiration, and the N2 flows into these air sacs. Gases in these air sacs
are rich in O2 and relatively low in CO2. The posterior sacs initiate the first expiration, with
valving that directs the flow with the N2 into the gas-exchanging parabronchi region of the
lung. Here the composition of the respiratory gases is modified to suit the metabolic needs
of the bird. Next, the anterior sacs inflate to create a second inspiration, with the N2 gas
now drawn into those air sacs. Finally, with second expiration resulting from the anterior
sacs and valving control, the gas is expelled to the outside atmosphere. Thus, in birds, it
requires two complete respiratory cycles to move air through the entire system. This
remarkable pattern of gas flow through the avian lung is achieved through both
aerodynamic mechanisms and valving properties of the air sacs. The end result is that gas
flow is continuous and unidirectional from the mediodorsals through the parabronchi to the
medioventrals.
3. Crosscurrent blood flow at the parabronchus. The anatomic arrangement of airflow
through the gas exchanging air capillaries in concert with the surrounding blood capillary
network is such that blood flow approaches the parabronchus at approximately right angles,
providing a crosscurrent system of gas exchange. Blood in the capillaries becomes
oxygenated to varying degrees depending on how far along the parabronchus the blood
capillary is located.
Check your understanding
1. What are the four possible steps in external respiration?
2. Do fish create flow-through breathing, and how does gill countercurrent flow aid gas
exchange?
3. Compare respiratory systems of frogs and non-avian reptiles.
4. Compare mammalian and bird respiratory systems (structures and methods of
ventilation).

CIRCULATORY SYSTEMS
Evolution of Circulation
Most multicellular organisms with specialized cells need some form of internal transport to
move important molecules and cells from one tissue to another in a reasonable amount of
time. Transported molecules in animals include gases, nutrients, wastes, hormones and
heat in endothermic animals (“warm-blooded” ones such as birds and mammals that
regulate body temperature via internal heat production), and also in some ectothermic
animals (“coldblooded” ones whose body temperatures depend on external sources).
Circulatory systems evolved to overcome the limits of diffusion which is a slow process. For
single-celled organisms and very small animals such as rotifers, movement of molecules
occurs primarily by diffusion, since distances are quite small and metabolic demands are not
high. However, as animals evolved thicker and larger bodies and higher metabolic rates, the
need for internal circulatory systems became paramount because of diffusion limits.
Circulatory systems overcome the slowness of diffusion by the much faster process of bulk
transport: the movement of the medium that contains the molecules (and cells) of interest.
General Features and Principles of Circulatory Systems
Circulatory systems have up to three distinct components: fluid, pump, and vessels.
1. The fluid itself, which carries the transported molecules and cells; typically called blood
or hemolymph. (Greek word: hemo means for blood).
2. A pump to move the fluid; dedicated pumps are usually called hearts (Greek word: cardio
for heart).
3. Vessels to carry the fluid between the pump and body tissues; these are called vascular
components. However, not all three components are necessary for some types of
circulation. In particular, completely enclosed vessels are absent in many animal groups.
Also, biological pumps are not always distinct dedicated organs (hearts).
Circulatory systems can be open or closed. Traditionally, internal circulation of fluids is
divided into two broad categories:
• Open systems (Figure 1), in which the fluid— called hemolymph—moves via pumping
through vessels that open like garden hoses into extracellular spaces among the tissues,
bathing them directly for molecular exchanges with cells. The entire space filled with
hemolymph is called the hemocoel, which may be subdivided into smaller spaces called
sinuses. The fluid may be moved by body movements, by cilia, or by hearts; the latter may
have outflowing vessels called arteries, and intake pores called ostia or intake vessels called
veins. Various versions of open systems are found in many animal groups, including most
mollusks and all arthropods
• Closed systems in which the fluid— called blood—exits a heart through vessels that are
continuous all the way back to the intake side of the heart. The delivery (outgoing) vessels
branch and become smaller and smaller until they become tiny leaky capillaries, where flow
slows down and exchange of materials occurs with body cells. These vessels then merge and
become larger in size and fewer in number as blood is returned to the heart. Capillaries are
widely regarded as the primary structure distinguishing a closed from an open system
because, while some open systems have delivery vessels that branch into quite small ones,
they are not contiguous with return vessels. Closed systems are found in several animal
groups, including cephalopod mollusks, annelids, and vertebrates.
Circulatory Fluids and Cells
Circulatory fluids are divided into two components: a liquid called plasma, primarily water
containing a variety of dissolved and dispersed molecules, and cellular elements, of which
there may be several specialized kinds. In vertebrates, the three types of specialized cellular
elements suspended in the plasma are: (1) erythrocytes (or red blood cells, for oxygen
transport), (2) leukocytes (or white blood cells, for immunity), and (3) thrombocytes or
platelets (for clotting).
Plasma
Plasma typically consists of 90% or more water, which serves as a medium for a large
number of organic and inorganic substances being carried in the fluid. In mammals, the
most plentiful organic constituents are the plasma proteins, which compose 6 to 8% of
plasma’s total weight, compared to about 1% for inorganic constituents (Figure 2). The most
abundant electrolytes (ions) in virtually all animal plasmas are Na+ and Cl−. There are
smaller amounts of HCO3−, K+, Ca2+, and others. The most notable functions of these ECF
ions are their roles in membrane potential, osmotic distribution of fluid between the ECF
and cells, and buffering of pH. The remaining small percentage of plasma is occupied by
nutrients (for example, glucose, amino acids, lipids, and vitamins); waste products (such as
creatinine, bilirubin, and urea in mammals); dissolved gases (O2 and CO2); and hormones.
Most of these substances are merely being transported and have no functions in the
plasma.
Non-Specific Functions of Plasma Proteins:
1. Colloid osmotic pressure: Plasma proteins establish an osmotic gradient between the
blood (where they are present) and interstitial fluid (where they are absent). This colloid
osmotic pressure is the primary force responsible for limiting the loss of plasma from
the capillaries into the interstitial fluid, which helps maintain plasma volume.
2. Buffering. Plasma proteins are partially responsible for the plasma’s capacity to buffer
changes in pH.
In vertebrates, there are three major groups of plasma proteins, which are classified
according to their various physical and chemical properties:
1. Fibrinogen is a key factor in the blood clotting process.
2. Albumins, the most abundant of mammalian plasma proteins, bind many substances (for
example, bilirubin, bile salts, and fatty acids) for transport through the plasma and
contribute most extensively to the colloid osmotic pressure by virtue of their numbers.
3. Globulins come in three forms—alpha (𝛂), beta (𝛃), and gamma (𝛄)—which act as:
• Transporters. Specific α- and β-globulins bind and transport a number of substances in the
plasma, such as thyroid hormone, cholesterol, and iron. The most common is transferrin,
which binds and transports iron atoms.
• Clotting agents. Many of the factors involved in the process of blood clotting are α- or β-
globulins.
• Regulators. Inactive proteins that are precursors of regulators such as hormones, and that
are activated as needed by specific signals, belong to the α-globulin group (for example, the
α-globulin angiotensinogen is activated to angiotensin, which plays an important role in
regulating blood pressure and salt balance in the body).
• Immune effectors. The γ-globulins are the immunoglobulins (antibodies), which are
crucial to vertebrate defense mechanism. These proteins are predominately synthesized by
the liver. Some are produced by vascular endothelial (lining) cells.
In many animals, other crucial types of circulatory proteins function as respiratory pigments.
These are oxygen-binding proteins critical for transporting O2 for cellular respiration.
Respiratory pigments in animals vary considerably by phylum and may exist is one or more
isoforms in a particular species. The two most common ones are hemoglobins, proteins in
vertebrates and many non-vertebrates that use an iron atom to bind an O2 molecule; and
hemocyanins, proteins in many mollusks and arthropods such as crustaceans, that use two
copper atoms to bind one oxygen molecule. In many animals, however, these proteins are
not in the plasma itself but are contained in specialized cells. If they contain hemoglobin,
which is reddish when oxygen is bound, these cells are called erythrocytes (erythro, “red”).
Erythrocytes
Each milliliter (mL) of vertebrate blood contains numerous erythrocytes (or red blood cells),
for example, about 3 billion per mL in chickens, 7 billion per mL in cows and pigs and 10
billion per mL in horses. The main function of erythrocytes is to transport O2 from the lungs
or gills to the tissues. In most vertebrates, these cells are oblong oval (ovoid) shapes (Figure
3), with amphibians and lungfish having the largest. In contrast, mammalian erythrocytes
are flat, disc-shaped (biconcave) cells without nuclei, indented in the middle on both sides
like a doughnut with a flattened center instead of a hole (Figure 2).
A mammalian red blood cell is mainly a plasma-membrane enclosed sac full of hemoglobin
with the exclusion of almost everything else including nucleus, other organelles, or
ribosomes. These mammalian cells cannot use the O2 they are carrying for energy
production since they lack the mitochondria. Instead, they rely entirely on glycolysis for ATP
formation
Erythrocytes also contribute to CO2 transport in two ways:
1. Bicarbonate production: The mature mammalian erythrocyte retains glycolytic enzymes
and carbonic anhydrase (CA). CA is crucial in CO2 transport as it catalyzes a key reaction
that ultimately leads to the conversion of metabolically produced CO2 into bicarbonate ion
(HCO3−), which is the primary form in which CO2 is transported in the blood.
2. Hemoglobin also contributes by binding CO2, although it does not carry as much of this
gas as it carries O2. CO2 binds to the protein itself (the globin), not the iron.
Hemoglobins and erythrocytes have additional transport functions. In addition to carrying
CO and O2, hemoglobin and erythrocytes can also transport or regulate the following:
• Bicarbonate (HCO3−),
• H+ from ionized carbonic acid,
• Nitric oxide (NO).
• Hydrogen sulfide (H2S).
Hemopoietic tissues continuously replace worn-out erythrocytes. Avian and mammalian
erythrocytes have a short life span, presumably because they have nonfunctioning nuclei (in
birds) or no nuclei (in mammals). For example, they survive an average of only about 100 to
110 days in domestic mammals, and 30 days in a chicken. During this short life span, the
cell’s plasma membrane, which cannot be repaired, becomes fragile as the cell repeatedly
squeezes through capillaries. One organ involved with erythrocyte regulation is the spleen.
It has two important roles: 1. Removal of old red cells. Macrophages engulf and destroy the
dying cells. 2. Red cell reservoir. The spleen can store healthy erythrocytes in its pulpy
interior; it also serves as a reservoir site for platelets and contains an abundance of
lymphocytes, a type of white blood cell. In many mammals, the stored erythrocytes form a
reserve of oxygen that can be released (by contraction of the organ) during locomotory
activity. In horses, for example, splenic contraction during exercise can double the
hematocrit. Because erythrocytes cannot divide to replenish their own numbers, the old
ruptured cells are replaced by new cells produced in an erythrocyte factory, called
hemopoietic tissues. The kidney and spleen produce these cells in bony fishes while in birds
and mammals, it is the bone marrow— the soft, highly cellular tissue that fills the internal
cavities of bones. Regions of bone marrow called red bone marrow normally generate new
red blood cells, a process known as erythropoiesis, to keep pace with the demolition of old
cells (at the amazing rate of 2 to 3 million per second in humans). In adult humans, red
bone marrow is found in the sternum (breastbone), vertebrae (backbone), ribs, base of the
skull, and upper ends of the long limb bones. Red marrow not only produces red blood cells
but is the ultimate source for leukocytes and platelets as well.
Leukocytes
Leukocytes, or white blood cells, are the mobile units of vertebrate immune systems.
Thrombocytes and platelets
The third type of blood cell is the thrombocyte (a living cell) or platelet (a cell fragment),
which serves in the clotting mechanism. Thrombocytes are cells found in all vertebrates
except mammals; these cells circulate in an inactive state, and when activated by an injury
to nearby tissue, they begin to break up into platelet-like fragments. Mammals are different
in that the precursor cells become platelets, which become the primary inactive form that
circulates in the blood. Specifically, platelets are small cell fragments (about 2 to 4 μm in
diameter) that are shed off the outer edges of extraordinarily large (up to 60 μm in
diameter), bone-marrow bound cells known as megakaryocytes, each of which typically
produces about 1,000 platelets. Megakaryocytes are derived from the same stem cells that
give rise to the erythrocytic and leukocytic cell lines. Platelets are essentially detached
vesicles containing portions of cytoplasm wrapped in plasma membrane. Platelets remain
functional for less than two weeks, at which time they are removed from circulation by
macrophages, especially those in the spleen and liver, and are replaced.
Circulatory Pumps: Evolution
Circulating body fluids require some form of pump. At least four different types of pumping
mechanisms have evolved, as follows:
1. Flagella: Internal fluids may be moved slowly by beating flagella on epithelial cells.
2. Extrinsic muscle or skeletal pumps: Fluids may be moved by motions of muscles or
skeletal elements that are not part of the circulatory system itself. Most often,
extrinsic pumping occurs only during locomotion. This is an important mechanism in
tails of hagfish and legs of tall animals such as humans.
3. Peristaltic (tubular) muscle pumps: Peristaltic pumping occurs when muscles in the
walls of vessels contract in a moving wave that pushes fluid in front of it. By repeated
cycles of this action, fluid is moved in one direction. These pumps are called “hearts”
 if they occur in specialized sections of vessels. This is the pumping method in many
annelids and arthropods.
4. Chamber muscle pumps: These are the more familiar form of hearts, consisting of a
chamber or chambers with muscles to squeeze the fluid within. Chamber hearts are
the primary pumps in all vertebrates. Unlike directional peristaltic pumps, chamber
pumps usually need one-way valves to create flow in one direction to prevent
backflow when the pump relaxes. In some animals such as arthropods, the heart has
a single chamber. All vertebrates have a minimum of two types of chambers: an
atrium, which collects returning fluid, and a ventricle that provides the primary force
for outgoing fluid. (Figure 4)
Vertebrate Hearts
The primitive systemic heart of vertebrates is thought to have begun with two chambers,
one atrium to collect returning blood and one ventricle to pump to the body. Fishes have
this basic design, but one or two auxiliary chambers have evolved. Blood of all jawless and
jawed fishes first enters a chambered extension of the atrium called the sinus venosus,
which collects blood from the veins before entering the adjacent atrium. In jawed fishes,
blood leaving the ventricles enters an extension forming a fourth chamber, the conus
arteriosus (in cartilaginous fish) or bulbus arteriosus (in bony fish), which dampens the
pulsatile pressure output of the ventricle (a function taken over by the aorta in reptiles
(including birds and mammals). Although these fish hearts have four chambers, they are
considered to have two primary chambers with two auxiliary chambers (Figure 5). A
significant change in vertebrate hearts began when the first air-breathing fishes evolved.
The crucial feature that drove this change was the evolution of a separate circuit, called the
pulmonary circulation, from the heart to the newly evolved lungs and back. The two primary
chambers began to subdivide with internal septa to support this separate circuit, with one
side of the atrium collecting blood from the body and one side collecting from the lungs,
and with one side of the ventricle pumping blood to the lungs and one side pumping to the
body. This culminated in the hearts of birds and mammals, which have two completely
separate atrium–ventricle pairs, which pump to the pulmonary circulation to the lungs and
the systemic circulation to the rest of the body.
How the heart functions
Avian and mammalian hearts are dual pumps. These hearts have four chambers, an upper
and a lower one, within each half (Figure 6a). The upper chambers, the atria (singular,
atrium), receive blood returning to the heart and transfer it to the lower chambers, the
ventricles, which pump the blood from the heart. The vessels that return blood from the
tissues to the atria are veins, and those that carry blood away from the ventricles to the
tissues are arteries. The two halves of the heart are separated by the septum, a continuous
muscular partition that prevents mixture of blood from the two sides of the heart. This
separation is extremely important, because the right half of the heart is receiving and
pumping O2 depleted CO2-rich blood whereas the left side of the heart receives and pumps
O2-rich CO2-poor blood.
Blood returning from the systemic circulation enters the right atrium via large veins known
as the venae cavae. The drop of blood entering the right atrium has returned from the body
tissues, where O2 has been extracted from it and CO2 has been added to it. This partially
deoxygenated blood flows from the right atrium into the right ventricle, which pumps it out
through the pulmonary artery to the lungs. Thus, the right side of the heart pumps blood
into the pulmonary circulation. Within the lungs, the drop of blood loses its extra CO2 and
picks up a fresh supply of O2 before being returned to the left atrium via the pulmonary
veins. This O2-rich blood returning to the left atrium subsequently flows into the left
ventricle, the pumping chamber that propels the blood to all body systems except the
pulmonary circulation of the lungs; that is, the left side of the heart pumps blood into the
systemic circulation. The large artery carrying blood away from the left ventricle is the aorta
(Figure 6a & b). Major arteries branch from the aorta to supply the various tissues of the
body. Both sides of the heart simultaneously pump equal amounts of blood. The pulmonary
circulation is a low pressure, low-resistance system, whereas the systemic circulation is a
high-pressure, high-resistance system. Therefore, even though the right and left sides of the
heart pump the same amount of blood, the left side performs more work because it pumps
an equal volume of blood at a higher pressure into a higher-resistance system. Accordingly,
the heart muscle on the left side is much thicker than the muscle on the right side, making
the left side a stronger pump (Figure 7).
Blood flows through vertebrate hearts in one fixed direction through the heart. The
presence of one-way valves ensures this unidirectional flow of blood. Heart valves are
positioned so that they open and close passively because of pressure differences, similar to
a one-way door (Figure 8). A forward pressure gradient (that is, a greater pressure behind
the valve) forces the valve open, whereas a backward pressure gradient (that is, a greater
pressure in front of the valve) forces the valve closed. These valves are in all vertebrate
hearts; two are shown in a cartilaginous fish in Figure 5. The right and left atrioventricular
(AV) valves are positioned between the atrium and the ventricle on the right and left sides,
respectively (Figure 9). These valves allow one-way flow from the atria into the ventricles
during ventricular filling (when atrial pressure exceeds ventricular pressure). The other two
valves, the aortic and pulmonary valves, are located at the juncture where the major
arteries leave the ventricles. They are known as semilunar (“half-moon”) valves because
they consist of three cusps, each resembling a shallow half-moon–shaped pocket. These
valves are forced open when the left and right ventricular pressures exceed the pressure in
the aorta and pulmonary arteries, respectively, during ventricular contraction and emptying.
Closure results when the ventricles relax and ventricular pressures fall below the aortic and
pulmonary artery pressures. Even though there are no valves between the atria and veins,
backflow into the veins usually is not a significant problem, because (1) atrial pressures are
not much higher than venous pressures, and (2) the junctions of the veins and atria are
partially compressed during atrial contraction.
The bulk of the vertebrate heart wall is the myocardium (myo, “muscle”), a middle layer of
cardiac muscle lying between an endothelial layer (the endocardium) and a thin outer
sheath, the epicardium. In mammals, the myocardium consists of interlacing bundles of
cardiac muscle fibers arranged spirally around the heart circumference. The individual
cardiac muscle cells are interconnected to form branching fibers, with adjacent cells joined
end-to-end at specialized structures known as intercalated discs. Electrical impulses trigger
heart contraction. Once initiated, an impulse spread to all the other cells that are joined by
gap junctions so that they contract as a single functional syncytium (a group of joined cells
acting as one functional unit). It is either all the cardiac muscle fibers contract or none do. A
“half-hearted” contraction is not possible.
Circulatory Pathways and Vessels
Fishes
Water-breathing jawed fishes have a one-circuit flow pattern just discussed (Figure 10).

The flow to the gills is in series with the rest of the circulation, with the rest of the flow in a
parallel system. While useful for maximal gas exchange, series flow creates a problem
because the tiny diameters of the capillaries in the gills create an enormous resistance to
flow. Consequently, blood flow from the gills to the rest of the body tends to be somewhat
sluggish. This means that whereas there is sufficient oxygen in the blood, it is not rapidly
delivered to body muscles.
Hagfish (jawless fishes) are similar but have partially open systems with large sinuses in the
head and under the skin. They also have auxiliary hearts in veins of the head, abdomen, and
tail to assist return flow.
Air-breathing fishes such as lungfish evolved a new respiratory organ, the lung, in addition
to gills. This required a separate circuit, because the lung is not always used by these fishes.
This in itself would not be very efficient if the oxygenated blood returning from the lungs
were to mix with the deoxygenated blood returning from the systemic veins, or if the
oxygenated blood were to travel on to the gills. For this reason, the lungfish heart evolved
partial barriers or septa in the atrium and ventricle that subdivide those chambers into
somewhat separate pumping functions on the right and left sides. The septa reduce mixing
of oxygenated with deoxygenated blood. In lungfish, the flow to the lungs occurs after the
gills, where the blood can either go to the body (during water breathing), or be diverted to
the lungs (during air breathing), and is summarized as follows:

Amphibians
As the first amphibians evolved to live part time on land, gills were lost in adults of some
species which now use their skins to absorb O2 when they are in water, and lungs when
they are in air. Thus, the pulmonary circulation evolved into a completely separate circuit,
going to the lungs and skin, with the systemic circulation going to the main body without
passing through a respiratory organ. The atrium is split completely into two chambers, such
that amphibians have essentially a three-chambered heart (although most retain a sinus
venosus and conus arteriosus). The single ventricle is not subdivided well except for some
modest folds, so that oxygenated and deoxygenated blood does mix somewhat in that
chamber (Figure 11).

Reptiles
Reptiles evolved into purely air-breathing animals, relying on lungs only. The heart lost the
auxiliary chambers of fishes and amphibians but retained the two atria that amphibians
have. However, the ventricle is different. In most reptiles, it is one large chamber but has
two large subchambers partially divided by thick muscle rather than a true septum: the
cavum arteriosum and cavum pulmonale. At the top of both (and connected to both) is a
small third subchamber, the cavum venosum. Flow through these subchambers can follow
two different pathways if the reptile is a diver (such as a turtle or sea snake) (Figure 12).
Blood flow while breathing air is as follows

During a dive, the lungs can be bypassed via the c. venosum, a useful adaptation when the
animal is holding its breath for long periods:

Birds and Mammals

The hearts of birds and mammals have a complete four-chambered structure. These four-
chambered hearts are two separate pumps fused together. Thus, mammalian and avian
blood travels with this pattern (Figure 13):

With the complete separation of pulmonary and systemic flow, all blood pumped by the
right side of the heart passes through the lungs for O2 pickup and CO2 removal. Then the
oxygenated blood pumped by the left side of the heart is parceled out in various
proportions to the systemic organs through the parallel vessels that branch from the aorta.
Circulatory Vessels
Arteries, which carry blood from the heart to the tissues, branch into a “tree” of
progressively smaller vessels, with the various parallel branches to different regions of the
body. When a small artery reaches the organ it is supplying, it branches into numerous
parallel arterioles, which provide flow control. Arterioles branch further within the organs
into capillaries, the smallest of vessels, across which all exchanges are made with
surrounding cells and which is the primary goal of the entire circulation. Capillaries rejoin to
form small venules, which further merge to form small veins that leave the organs. The
small veins progressively unite to form larger veins that eventually empty into the heart. The
arterioles, capillaries, and venules are collectively referred to as the microcirculation
because they are only visible microscopically.
TABLE 1: Features of Blood Vessels (with Human Values)

Check you Understanding

1. How do circulatory systems overcome the limits of diffusion?
2. What are the differences between open and closed circulatory systems?
3. What is the basic composition of plasma?
4. What are the major transport functions of vertebrate erythrocytes?
5. Describe four different pumping mechanisms for circulation that are not systemic
hearts.

EXCRETORY SYSTEMS
Evolution of Excretory Systems
One of the most crucial aspects of homeostasis is the maintenance of an internal aqueous
environment that is conducive to life. This “inland sea” is regulated within narrow limits to
maintain a beneficial composition of water and important solutes and a low level of wastes.
Dietary intake, metabolic products, and losses or excess intake of water and ions frequently
create imbalances in the internal environment. Thus, these animals may need to excrete
excess salt (as well as wastes) while conserving body water.
Primary Functions of Excretory Organs
1. Maintenance of proper internal levels of inorganic solutes (Na+, K+, Cl−, H+, CO2, and so
forth). Even minor fluctuations in concentrations of some of these electrolytes in the
extracellular fluid can have profound influences on metabolism. For example, changes in
ECF concentration of K+ can potentially lead to fatal cardiac dysfunction.
2. Maintenance of proper plasma water volume, important for proper circulatory-fluid
pressure and general state of tissue hydration.
3. Removal of nonnutritive and harmful substances resulting from metabolism (ammonia,
urea, bilirubin, and so forth) or ingestion (such as plant alkaloids, drugs), and removal of
hormones after they have had their desired effect. This must be done without losing useful
organic molecules such as nonhormone proteins and glucose.
4. Maintenance of osmotic balance (which results from a combination of water and
dissolved solutes) by selective retention and excretion of water and ions.
In mammals, kidneys have the following additional functions:
5. Secretion of erythropoietin, a hormone that stimulates red blood cell production.
6. Secretion of renin, a hormone important for salt conservation.
7. Conversion of vitamin D into its active form.
8. Excretion of pheromones for sexual signaling, marking territories, and so forth.
As aquatic animals evolved larger sizes and greater complexity, diffusion and membrane
transport became inadequate for removing wastes from internal body fluids. To be free to
move about in an often dry and ever-changing external environment, animals had to evolve
more elaborate mechanisms to maintain internal fluid homeostasis. Thus, larger and more
complex aquatic animals, and all terrestrial ones, evolved specialized tubules lined with
transport epithelia dedicated to excreting and selectively retaining key molecules of the
body. In the animal kingdom, four organ systems can be involved in excretion and retention:
1. Respiratory systems (gills and lungs), which help regulate CO2. Gills can also help remove
other solutes such as ammonia and HCO3−.
2. Digestive systems, which remove not only undigested food but also some end products of
internal metabolism such as biliverdin from the vertebrate liver. The liver in this case is
acting as an excretory organ. Intestinal tract epithelia may also help regulate ions and water,
and in some animals the gut receives the output of renal organs.
3. Integument (skin) and glands, some of which can excrete organic wastes as secondary
functions (such as sweat glands in humans), and others that evolved primarily to excrete
excess inorganic ions (salt glands of brine shrimp and marine reptiles). The skin of many
amphibians also regulates salt and water uptake.
4. Renal organs (renalis, Latin for “kidney”) with tubules that filter body fluids and regulate
water, ions, and many organic substances, and then selectively reabsorb or secrete these
molecules. The output of renal organs is called urine. These organs, together with ductwork
and any bladders (urine-storage chambers), compose the urinary system.
Important Nitrogenous wastes
Ammonia: it is generally formed the deamination of proteins in aquatic animals. It is Soluble
in water and highly toxic. Animals which produce ammonia are known as ammonotelic.
The process of excretion of ammonia involves loss of considerable amount of water. That is
the reason why ammonotelic excretion is found in aquatic animals. Examples: Hydra,
Teleosts
Urea: It is characteristic of terrestrial animals and in higher animals, it produced in liver by
the deamination process. This is known as ornithine cycle and animals which produce urea
are known as ureotelic. The process of excretion requires less water making it suitable for
terrestrial mode of life with tendency to conserve water. Example. Man, Elasmobranch fish.
Uric acid: It is characteristic of animals where conservation of water is needed. Uric acid is
formed in liver due to absence of arginase enzyme. It is formed from ammonia and purines
(adenine and guanine) in liver and kidney. In human beings, uric acid is formed by the
catabolism of purines. Animals which excrete uric acid are known as uricotelic e.g. birds,
insects and desert animals. It is less soluble in water, less toxic and can remain in the tissues
for long period making excretion of uric acid of greater advantage to land animals.
Other wastes:
• Tri-methyl amine- oxide: Soluble in water. E.g. Bony fishes.
• Guanine: By spider.
• Hippuric acid: mammals, formed by the combination of glycine.
• Ornithinic acid: Birds.
• Creatine: Derivative of creatine phosphate. E.g. mammals.
• Allontoin: Embryonic waste.
• Carbon dioxide: End product of respiration.
• Bilirubin: Toxic bile pigment formed in liver by dead RBCs.
Renal Excretory Organs: Overview
Renal organs have tubules that filter solutes and water from body fluids and subsequently
modify the fluid in the tubular lumen using transport epithelia, specifically for water and
solute homeostasis and waste removal. Renal tubules operate by two or more of four basic
renal processes (Figure 1):
1. Filtration, in which solutes are selectively separated from a solution by passing through a
boundary. Often this is a mostly nonselective process, in which some water with all its small
solutes passes through the barrier, except that cells and large molecules such as proteins
(and some water) remain behind, a process called ultrafiltration. Ultrafiltration is typically
driven by hydrostatic pressure.
2. Secretion, in which transport epithelia move (often actively) specific solutes into the
tubule lumen for excretion.
3. Reabsorption, in which transport epithelia move (often actively) specific solutes (and
often water) back into the body from the lumen.
4. Osmo-concentration, in which water is removed from the lumen fluid while leaving
solutes behind, producing an excretory fluid more concentrated (hyperosmotic) than body
fluids and thus conserving water.
Renal Organs
Several different kinds of renal organs have evolved, three recognized common types are—
protonephridia, meso- and metanephridia, Malpighian tubules—based on which body fluids
are processed and how.
1. Protonephridia (bundles of flame cells) use ultrafiltration driven by cilia, with
secretion and reabsorption. These are the types of specialized filtration system
thought to have evolved first in freshwater non-vertebrates.
2. Mesonephridia and metanephridia use ultrafiltration typically driven by fluid
pressure, with secretion, reabsorption, and occasionally osmo-concentration. These
tubules are in animals with two or more major fluid spaces—a coelom and a
circulatory fluid at a minimum. The tubules begin with a filtering capsule or funnel-
like opening that ultrafilter the circulatory fluid. This is followed by tubule segments
that perform selective secretion and reabsorption (and osmo-concentration in some
groups) and may empty via a connecting canal or ureter into a hindgut or a bladder.
In vertebrates, the renal tubules are called nephrons (Greek nephros, for “kidney”),
and they go through significant developmental changes in most groups. In all groups,
the first renal structure is a ciliated pronephric one, which becomes functional only
in larval fishes, amphibians, adult hagfish, and lampreys. In all other adult fishes and
amphibians, the pronephric tubules degenerate except the duct, which becomes the
foundation of new pressure driven mesonephric tubules (the kidneys). Finally, in
terrestrial vertebrates, both the pro- and mesonephric tubules form in embryos but
are replaced by the metanephric tubules (more adapted for water-limited life on
land). The mesonephric tubules, however, become the ducts of reproductive organs
in males. In other animals, many meso- and metanephridial tubules are assembled
together with connective tissue into large organs called kidneys, as in the case in
“higher” vertebrates.
3. Malpighian tubules begin filtration driven by active secretion of ions from an
arthropod’s hemolymph and then, in conjunction with the hindgut, use reabsorption
and sometimes osmo-concentration.
Vertebrate Urinary Systems and Extrarenal Organs
The urinary system consists of the urine-forming organs— the kidneys—and the structures
that carry the urine from the kidneys to the outside for elimination from the body (Figure 2).
Kidneys are paired organs that lie in the dorsal side of the abdominal cavity, one on each
side of the vertebral column. Only the mammalian kidney has a “kidney bean” shape while
mesonephric kidneys of bony fish are elongated. The kidneys of birds are divided into
cranial, middle, and caudal subdivisions, with the surface of the kidney covered in rounded
projections, the renal lobules. Each kidney is supplied by a renal artery and a renal vein.
Urine drains into the two ureters (ducts walled with smooth muscle), one carrying urine
from each kidney to a bladder (in fish, amphibians, and mammals) or hindgut (in reptiles
including birds), which temporarily stores urine (and in some animals may modify it).
Periodically urine is emptied to the outside; in vertebrates with bladders, this is through
another tube, the urethra (which in male mammals serves both as a route for eliminating
urine and as a passageway for semen from the testes).
The Nephron
A nephron is the smallest functional unit capable of the kidney’s basic functions. Nephrons
are found in all vertebrate kidneys, and each kidney consists of numerous nephrons (for
example, about 1.25 million in pigs, 1 million in humans, 0.5 million in dogs, 0.25 million in
cats) bound together by connective tissue. Each nephron consists of the tubules and an
associated vascular (blood vessel) component, both of which are intimately related
structurally and functionally (Figure 3). The arrangement of nephrons within mammalian
kidneys gives rise to two distinct regions—an outer, granular-appearing region, the renal
cortex, and an inner, striated region called the renal medulla (Figure 2b). Some mammals
(generally small ones such as rodents and rabbits) have a unipapillary medulla, a single,
striated, cone-shaped body (the papilla). Larger mammals (such as dogs and humans) have a
compound medulla, containing several striated appearing triangles, the renal pyramids
(Figure 2b). On entering the kidney, the renal artery systematically subdivides to form many
small vessels known as afferent arterioles, one of which supplies each nephron. The afferent
arteriole delivers blood to the glomerulus, a ball-like knot of capillaries (in the cortex in
mammals) through which part of the water and solutes are filtered from the blood passing
through. The glomerular capillaries rejoin to form another arteriole, the efferent arteriole,
through which blood that was not filtered into the tubular component leaves the
glomerulus. At the glomerular capillaries, no O2 or nutrients are extracted from the blood
for use by the kidney tissues, nor are waste products picked up from the surrounding tissue.
The efferent arteriole then subdivides into the peritubular capillaries, which supply the renal
tissue with blood and are important in exchanges between the tubular system and blood
during conversion of the filtered fluid into urine. These capillaries, as their name implies
(peri, “around”), are intertwined around the tubular system. The capillaries rejoin to form
venules that ultimately drain into the renal vein, by which blood leaves the kidney.
Returning to the glomerulus, filtered fluid leaving the capillaries passes through the tubules
of the nephron. The tubules are hollow, fluid-filled tubes formed by a single layer of
epithelial cells. Even though each tubule is continuous, it is specialized into various
segments with different structures and functions along its length. The first three basic renal
processes—filtration, reabsorption, secretion are involved in the formation of urine in all
vertebrates, with the fourth (osmo-concentration) found in birds and mammals.
• Bowman’s (or glomerular) capsule and filtration: Around a glomerular capillary bed is an
expanded, double-walled cup-shaped invagination called Bowman’s (or glomerular) capsule
that collects the fluid filtered from the capillaries there. This is known as glomerular
filtration: As blood flows through the capillaries, blood pressure forces protein-free plasma
into Bowman’s capsule. This ultrafiltration process is the first step in urine formation in
most vertebrates and is normally continuous. This filtration process is non-discriminating;
that is, with the exception of blood cells and most plasma proteins, all constituents within
the blood—H2O, nutrients, electrolytes, wastes, dietary toxins, small proteins, peptides
such as hormones, and so on—are non-selectively filtered.
• Proximal tubule and reabsorption/secretion: From this capsule, the filtered fluid passes
into the proximal tubule, which lies within the cortex and is highly convoluted throughout
much of its course. Here, substances of value such as glucose, amino acids, and much of the
water are returned to the peritubular capillary plasma. This selective movement of
substances from inside the tubule into the blood uses energy and is called tubular
reabsorption. Reabsorbed substances are not lost from the body in the urine but are carried
instead by the peritubular capillaries to the venous system and then to the heart to be
recirculated. Of the volume of plasma filtered per day, generally over 90% of the water and
100% of the glucose and amino acids are reabsorbed in mammals, with the remaining fluid
eliminated as urine. In general, substances that need to be conserved are selectively
reabsorbed, whereas unwanted substances that need to be eliminated remain in the urine.
The proximal tubule also performs tubular secretion, the selective transfer of substances
from the peritubular capillary blood into the tubular lumens, a second route for substances
to enter the renal tubules from the blood.
Loop of Henle (or nephron loop) and osmo-concentration. Next, the tubule in birds and
mammals forms a sharp U-shaped or hairpin loop that dips into the renal medulla. The
descending limb of this loop of Henle plunges from the cortex deep into the medulla; the
ascending limb traverses back up into the cortex, running countercurrent to the descending
limb. This loop is a major adaptive feature of avian and mammalian nephrons, resulting in
the medulla region to become highly concentrated in NaCl (and urea in mammals). The
osmo-concentration process allows avian and mammalian kidneys to recover and conserve
more water if necessary, further concentrating the waste products in the urine. This process
is often classified as a type of tubular reabsorption.
• Distal tubule and reabsorption/secretion and osmo-concentration. The tubule once again
becomes highly coiled to form the distal tubule, which also lies entirely within the cortex in
mammals (This tubule is absent in marine bony fishes). It also performs selective
reabsorption and/ or secretion, and participates in osmo-concentration.
• Collecting duct and osmo-concentration. The distal tubule empties into a collecting duct,
each of which in mammals drains fluid from up to eight separate nephrons. Each collecting
duct releases its fluid contents (urine) into ureters in most vertebrates, though in mammals,
each duct empties into the renal pelvis (Figure 2), a cavity at the inner core of each kidney.
In birds and mammals, this duct is also important for osmo-concentration.
• Juxtaglomerular apparatus and regulation. The ascending limb returns to the glomerular
region of its own nephron, where it passes through the fork formed by the afferent and
efferent arterioles. Here, both the tubular and vascular cells are specialized to form the
juxtaglomerular apparatus, or JGA (juxta, “next to”), a structure that lies next to the
glomerulus and plays an important role in sensing blood osmolarity and pressure and
regulating kidney function.
The Nephron in Various Vertebrates
Fishes
Sharks and their relatives (elasmobranchs) are isosmotic or slightly hyperosmotic relative to
seawater. Thus, they face the problem of excess NaCl entering through the gills and diet, but
they do not have a problem with osmotic water loss. The gills are relatively impermeable to
urea and (trimethylamine oxide) TMAO, in part because of high cholesterol content. Also,
the nephrons reabsorb most of these osmolytes from the filtrate, excreting only what is
necessary for nitrogen balance. Although the nephrons have only glomeruli, proximal, and
distal tubules (Figure 4a), they are among the most complex known, apparently exhibiting
multiple countercurrent arrangements that are probably related to this reabsorption ability.
Beyond this, however, extrarenal organs perform most other excretion and osmoregulatory
roles. Gills are thought to remove some of the excess NaCl, but in particular, these fish have
a specialized hindgut organ called the rectal gland, which has numerous blind-end tubules
that excrete a hypertonic fluid high in NaCl. It actively transports salt out of the blood, but it
is not considered a renal organ, because no filtration or waste excretion is involved.
Marine bony fishes use gills for most excretion and retention processes In contrast to
elasmobranchs, most marine bony fishes are highly hypo-osmotic compared to seawater, so
they face constant influx of excess salt through the gills and diet, and constant water loss
through the gills. The gills of these fishes are responsible for most of the functions we
typically associate with kidneys. To reverse the water loss, these fish must drink seawater.
Initially, this also creates an excess of salt in the blood. The gills compensate for this excess,
using specialized epithelial chloride cells, which actively transport NaCl outward faster than
water leaks out. The kidneys play a minor role in correcting salt imbalances: The vast
majority of marine fishes cannot produce a sufficiently hyperosmotic urine that would
remove NaCl and conserve water. Kidneys in most species have small glomeruli and
proximal tubules but no distal tubules (which would unnecessarily create a hypo-osmotic
urine) (Figure 4b). Thus, the gills serve as extrarenal osmoregulatory and excretory organs.
A few aglomerular species (Figure 4c), including many Antarctic fish, lack glomeruli and so
do not use ultrafiltration. These species, such as toadfish, may have lost their glomeruli
through evolution because they (and all marine bony fishes) produce very little urine. What
urine they do produce begins initially by salt and water secretion into the proximal tubule
lumen. Furthermore, the lack of glomeruli in some Antarctic fish may help them retain the
small antifreeze glycoproteins they have in their blood.
Freshwater bony fishes must maintain an internal osmotic pressure far above that of the
environment—that is, they are hyperosmotic—and are faced with constant influx of water
through the gills and mouth (from eating, because they rarely drink). Accordingly, their
kidneys have evolved to excrete a voluminous, highly dilute (hypo-osmotic) urine. Kidneys
have large glomeruli with nephrons having proximal tubules, sometimes ciliated
intermediate tubules, distal tubules, and collecting ducts (Figure 4d). Most of these
segments reabsorb nutrients and minerals; the distal tubule helps create the hypo-osmotic
urine by removing ions from the lumen. Dietary intake and active transport by the gills
brings in NaCl and other ions to replace those lost in the urine.
Amphibians
Amphibians demonstrate the transition to a life on land. Metanephric nephrons in adult
amphibians are similar to the mesonephric ones of freshwater fish (Figures 4b and 4e), with
similar functions (to excrete water and reabsorb ions and nutrients) but with the added
function of urea excretion. Also unlike fish, terrestrial frogs can shut down glomerular
filtration to almost zero when faced with dehydration (a similar shutdown occurs in
mammals under acute stress and severe dehydration).
Moreover, the urinary bladder in terrestrial amphibians has a secondary role, that of a
temporary water reservoir. After the salty urine reaches the bladder, active transporters
move the salt back to the blood, leaving highly purified water behind (much like the
functioning of the thick ascending loop of Henle in mammals). Certain frogs such as the
Australian water-holding frog that burrow and estivate store this nearly pure water to be
returned to the blood when needed. The native human inhabitants of Australia have long
made use of this as a source of safe drinking water in the desert, released by squeezing the
animal!
Reptiles
Non-avian reptiles have nephrons similar to aquatic vertebrates in having capsules, proximal
tubules, ciliated intermediate tubules, distal tubules, and collecting ducts (Figure 4f). The
ureters carry urine in a liquid or semisolid form into the cloaca, the final chamber of the
hindgut. In order to remove excess water from the body, freshwater reptiles have larger
glomeruli compared to terrestrial species. For the latter, without a loop of Henle, the
nephrons cannot produce a significantly hyperosmotic urine to conserve body water.
However, they can conserve water in three ways. (1) Uric acid as the primary nitrogenous
waste conserves water. (2) The cloaca or lower intestine can reabsorb some water by first
transporting salt. This precipitate the uric acid left behind even further, creating a more
solid urine, although it usually does not make a hyperosmotic urine. (3) Marine and some
desert reptiles (non-avian) have an extrarenal organ, the nasal salt gland that is dedicated to
excreting a highly salty fluid by the same mechanisms found in birds. For marine species,
NaCl is the primary salt, but glands of herbivorous lizards also excrete KCl to compensate for
the high potassium content of ingested plant food.
Birds
Bird kidneys are also usually dominated by so-called reptilian type nephrons (Figure 4g),
which have the same segments as (non-avian) reptile nephrons. However, birds also have
some so-called mammalian type nephrons with loops of Henle that can form a concentrated
urine (Figure 4h). Most birds form only modestly hyperosmotic urines, but much of their
primary nitrogenous waste is uric acid. Most of this uric acid precipitates as crystals (as uric
acid is inherently insoluble), which exert no osmotic pressure but can potentially damage
the nephron because of their “spiky” structure. For this reason, the precipitated uric crystals
are then covered by a protein coat (albumin) to form urate balls. These are sufficiently small
enough to be filtered through the pores into the capsule.
Salt Glands: Most marine birds, which must drink seawater, also have a nasal salt gland
located near the eyes, with ducts leading to the nasal passages (Figure 5). These glands
contain blind-end tubules lined with active salt-secreting cells that apparently transport
NaCl out of the blood without concomitant osmotic water movement. Unlike kidneys but
like shark rectal glands, these extrarenal cells perform no filtration or waste excretion;
moreover, they are not constantly active but rather work only when the bird is dehydrated
or overloaded with salt. The NaCl concentration excreted by the salt gland depends on what
a particular species eats.
Mammalian Urinary System: Bladder Storage and Micturition
In mammals, amphibians, and fishes, urine formed in the kidneys is carried through the
ureters to the urinary bladder. Urine is temporarily stored in the bladder, which is emptied
by micturition.
The mammalian bladder wall consists of smooth muscle lined by transitional epithelium
with special cells called umbrella cell. As is characteristic of smooth muscle, bladder muscle
can stretch tremendously without a buildup in bladder wall tension. In addition, the highly
folded bladder wall flattens out during filling, to increase bladder storage capacity. The
bladder smooth muscle is richly supplied by parasympathetic fibers, stimulation of which
causes bladder contraction. If the passageway through the urethra to the outside is open,
bladder contraction empties urine from the bladder. The exit from the bladder, however, is
guarded by two sphincters, the internal urethral sphincter and the external urethral
sphincter (Figure 6). The internal urethral sphincter consists of smooth muscle and is not
under cortical control. It is not really a separate muscle but instead consists of the last
portion of the bladder. Although not a true sphincter, it performs the same function. When
the bladder is relaxed, the arrangement of the internal urethral sphincter region closes the
outlet of the bladder. The external sphincter is skeletal muscle and is under cortical control
via a motor neuron, which is normally active to keep the sphincter closed.
Micturition, or urination, the process of bladder emptying, is governed by two mechanisms:
the micturition spinal reflex and cortical control. The micturition reflex is initiated when
stretch receptors within the bladder wall are stimulated. The greater the distension beyond
a certain minimum—250 to 400 mL in a human—the greater the extent of receptor
activation. Parasympathetic stimulation of the bladder causes it to contract. No special
mechanism is required to open the internal sphincter; changes in the shape of the bladder
during contraction mechanically pull the internal sphincter open. Simultaneously, the
external sphincter relaxes as its motor neuron supply is inhibited. Now both sphincters are
open, and urine is expelled through the urethra by the force of bladder contraction. In
addition to triggering the micturition reflex, bladder filling also sends signals to the brain
cortex, giving rise to the urge to urinate. Control of micturition by the brain can override the
micturition reflex so that bladder emptying can take place at the animal’s convenience
rather than at the time bladder filling first reaches the point of activating the stretch
receptors. Micturition is also an animal’s normal response to an extremely stressful
situation, because emptying the bladder reduces body weight. Urination cannot be delayed
indefinitely. As the bladder continues to fill, reflex input from the stretch receptors
increases with time. Finally, reflex inhibitory input to the external-sphincter motor neuron
becomes so powerful that it can no longer be overridden by cortical excitatory input, so the
sphincter relaxes and the bladder uncontrollably empties.
Check your understanding
1. What are the four major functions of excretory systems, and what are the four organ
systems that can serve this role?
2. Describe a vertebrate nephron and the major roles of the capsule + glomerulus,
proximal and distal tubules, loop of Henle, and collecting duct.
3. Compare excretory processes of marine elasmobranchs, marine bony fish, freshwater
bony fish, and amphibians.
4. Compare excretory processes of non-avian reptiles with birds.
5. Describe how the urine fills and then empties, including external regulatory features.

ENDOCRINE SYSTEMS
The endocrine system consists of several glands, all in different parts of the body (Figure 1).
Endocrine glands are ductless glands and their secretion is known as hormone. Along with
nervous system, it controls and coordinate the body functions and maintains a homeostasis.
Both endocrine and nervous systems collectively called neuro endocrine system. A hormone
is a chemical substance produced and released by nonneural endocrine cells or by neurons;
it exerts regulatory influences on the function of other, distant cells reached via the blood;
and it is effective at very low concentrations.
Classification of Hormones
Hormones are classified into three categories: peptides and proteins, amines, steroids
according to their biochemical structure (Table 1).
1. The peptide and protein hormones consist of specific amino acids arranged in a chain of
varying length; the shorter chains are peptides and the longer ones are categorized as
proteins. For convenience, we refer to this entire category as peptides. The majority of
animal hormones fall into this class; an example is insulin, which regulates blood glucose in
vertebrates.
2. The amines are modified amino acids. Melatonin, secreted by the vertebrate pineal
gland is derived from tryptophan, whereas the catecholamines and iodothyronines are
derived from tyrosine and include the hormones secreted by the vertebrate thyroid gland
and adrenal medulla.
3. The steroids are neutral lipids derived from cholesterol. These include the hormones
secreted by the vertebrate adrenal cortex and gonads (sex steroids such as estradiol and
testosterone), as well as some mammalian placental hormones
Solubility Characteristics of Hormone Classes
The chemical properties of a hormone, most notably its solubility, determine the means by
which the hormone is synthesized, stored, and secreted; the way it is transported in the
blood; and the mechanism by which it exerts its effects at the target cell, and typically, the
type of processes regulated (rapid versus long-term) and their half-lives in the circulation.
The following differences in the solubility of the various types of hormones are critical to
their function (Table 1).
• All peptides and catecholamines are hydrophilic (water loving); that is, they are highly H2O
soluble and have low lipid solubility.
• All steroid and thyroid hormones are lipophilic (lipid loving); that is, they have high lipid
solubility and are poorly soluble in H2O.
Hydrophilic hormones are transported dissolved in the plasma, whereas lipid-soluble
hormones are almost always transported bound to plasma proteins. Some plasma proteins
are designed to carry only one type of hormone, whereas other plasma proteins, such as
albumin, indiscriminately pick up any “hitchhiking” hormone.

TABLE 1 Peptide, steroid, and amine hormones of vertebrates

Hormone synthesis, storage and secretion
Because of their chemical differences, the means by which the various classes of hormones
are synthesized, stored, and secreted differ as follows.
Peptide Hormones
Peptide hormones are synthesized by the same method used for the manufacture of any
protein that is to be exported. Because they are destined to be released from the endocrine
cell, the synthesized hormones must be segregated from intracellular proteins by being
sequestered in a membrane-enclosed compartment until they are secreted. peptide
hormone secretion is controlled primarily by regulating the release of pre-synthesized,
stored hormone.
Steroid Hormones
Cholesterol is the common precursor for all steroid hormones; however, numerous species
cannot synthesize cholesterol and must obtain it from their diet. Unlike peptide hormones,
steroid hormones cannot be stored after their formation. Once formed, the lipid soluble
steroid hormones immediately diffuse into the circulatory system. Only the hormone
precursor, cholesterol is stored in significant quantities within steroidogenic cells.
Accordingly, the rate of steroid hormone secretion is controlled entirely by the rate of
hormone synthesis.

Amines
They are derived from the naturally occurring amino acid tyrosine. Both types of amines are
stored until they are secreted. Thyroid hormone also undergoes further processing once in
the peripheral circulation.
General Mechanisms of Hydrophilic and Lipophilic Hormone Action
The location of the receptors within the target cell, and the mechanism by which binding of
the hormone with the receptors induces a response, both vary, depending on the
hormone’s solubility characteristics. Receptor–hormone interactions can be grouped into
two broad categories based on the location of their receptors (Table 1):
1. Membrane receptors. The hydrophilic peptides and catecholamines, which are poorly
soluble in lipid, cannot pass through the lipid membrane barriers of their target cells.
Instead, they bind with specific receptors located on the outer plasma membrane surface of
the target cell. In turn, these receptors either alter the shape of adjacent ion channels
already present in the membrane, or activate second-messenger systems within the target
cell. Second messengers directly alter the activity of preexisting intracellular proteins,
usually enzymes, to produce the desired effect.
2. Internal receptors. The lipophilic steroids and thyroid hormone (in the free form, not
bound with a plasma protein carrier) easily pass through the surface membrane to bind with
specific receptors located inside the target cell. The receptors inside the cell are typically
transcription factors that regulate specific genes in the target cell that code for the
formation of new intracellular proteins. Some lipophilic hormones also have specific
receptors in the plasma membrane and cytosol of target tissues.
All lipophilic hormones (steroids and thyroid hormone) bind with intracellular receptors in
their target cells by activating specific genes that cause the synthesis of new proteins, as
summarized in Figure 2. Free lipophilic hormone (hormone not bound with its plasma-
protein carrier) diffuses through the plasma membrane of the target cell (step 1 in Figure 2)
and binds with its specific receptor inside the cell, either in the cytoplasm or in the nucleus
(step 2). Each receptor has a specific region for binding with its hormone and another region
for binding with DNA. The receptor cannot bind with DNA unless it first binds with the
hormone. Once the hormone is bound to the receptor, the hormone receptor complex
binds with DNA at a specific attachment site on the DNA known as the hormone response
element (HRE) (step 3). Different steroid hormones and thyroid hormone, once bound with
their respective receptors, attach at different HREs on DNA. Binding of the hormone
receptor complex with DNA “turns on” or activates a specific gene within the target cell
(step 4). This gene contains a code for synthesizing a given protein. The code of the
activated gene is transcribed into complementary messenger RNA (mRNA) (step 5). The new
mRNA leaves the nucleus and enters the cytoplasm (step 6), where it binds to a ribosome,
the “workbench” that mediates the assembly of new proteins. Here, mRNA directs the
synthesis of the designated new proteins according to the DNA code in the activated genes
(step 7). The newly synthesized protein, either enzymatic or structural, is released from the
ribosome (step 8) and produces the target cell’s ultimate response to the hormone (step 9).
By means of this mechanism, different genes are activated by different lipophilic hormones,
resulting in different biological effects.
Important Endocrine and their Hormones (Table 2)
Check your Understanding
1. List the three chemical classifications of vertebrate hormones and the properties that
describe them.
2. How do hormones produce their effects on a target cell?