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Topics to Review
• Macromolecules (monomer to polymer structure)
• Membrane transport proteins (carriers, pumps,
channels)
• Active Transport
• Diffusion
• Osmosis
• Simple epithelium
• Enzymes
• Hydrolysis
• Exocrine glands
Digestive System
• The digestive system allows your body to obtain
substances required to sustain life that your body
cannot make on its own including:
– monosaccharides, amino acids, nucleic acids, fats,
vitamins, electrolytes (ions) and water
• The alimentary canal or gastrointestinal (GI) tract is a
long muscular tube lined with epithelial tissue passing
through the body which is closed off at each end by a
sphincter of skeletal muscle
• Opens to the outside world therefore the lumen and
its contents are part of the external environment
• Its primary function is to move water, nutrients and
electrolytes from the external environment into the
body’s internal environment
The Digestive System
• Accessory organs and
exocrine glands (teeth,
salivary glands,
pancreas and the liver)
aid in the process of
digestion in the
alimentary canal by
physical manipulation of
food or through the
secretion of substances
into the GI tract
Anatomy of the Digestive System
• Begins with the oral cavity (mouth and pharynx) where
chewing and the secretion of saliva starts digestion
• Food moves through the GI tract (esophagus to anus)
– rings of smooth muscle act as sphincters to
separate the tube into segments (esophagus →
stomach → small intestine → large intestine) with
different functions
• Digestive secretions are added to the food by GI
epithelium, liver and pancreas, turning it into a soupy
mixture called chyme
• The products of digestion pass out of the lumen into
the ECF where they pass into blood or lymph for
distribution throughout the body
• Any material remaining in the lumen at the end of the
GI tract is defecated through the anus
Peritoneum
• 2 connective tissue membranes in the abdominal
cavity which protect the organs in the abdominal cavity
from damage by friction/abrasion
– Visceral peritoneum
• covers external surface of digestive organs
– Parietal peritoneum
• lines the internal wall of the abdominal cavity
• Between the 2 layers of the peritoneum is a peritoneal
cavity which is filled with the peritoneal fluid secreted
by the cells of each layer
– the fluid functions to lubricate digestive organs,
allowing them to slide across one another without
creating friction which would lead to inflammation
4 Basic Processes of the Digestive System
• Digestion
– mechanical and chemical breakdown of food
• Motility
– movement of material along the GI tract
• Secretion
– release of substances (hydrolytic enzymes, mucus,
acid, bicarbonate, water, ions) from salivary glands,
GI epithelial cells, hepatocytes or pancreatic acinar
cells into the GI tract lumen or ECF
• Absorption
– active or passive transfer of substances from the
lumen of the GI tract to ECF
• Processes are regulated by the nervous and
endocrine systems as well as paracrine signals
4 Basic Processes of the Digestive System
Wall of the Alimentary Canal
4 principle layers of the GI tract
• Mucosa (superficial)
– inner layer of epithelial, connective and muscular
tissues that faces lumen
• Submucosa
– loose connective tissue with blood and lymph
vessels and submucosal plexus of the Enteric
Nervous System
• Muscularis
– 2 layers of smooth muscle (superficial circular and
deeper longitudinal) responsible for motility which is
innervated by the myenteric plexus of the Enteric
Nervous System
• Serosa (deep)
– strong connective tissue membrane that maintains
the structural integrity of the alimentary canal
(visceral layer of the peritoneum)
Layers of the Alimentary Canal Wall
Mucosal Epithelium
• Simple epithelium
– absorptive cells use integral transporting proteins in
the apical and basal membranes to absorb ions,
water and nutrients out of the lumen into the body
by facilitated diffusion, primary and secondary
active transport processes
– secretory cells (endocrine and exocrine)
• exocytose digestive enzymes and mucus into
lumen for digestion and protection against the
autodigestion of the mucosa, respectively
• exocytose hormones and/or paracrine molecules
into the ECF for digestive regulation
– sensory cells act as mechano- and chemoreceptors
which detect the presence of food by the distension
of the GI wall and by the presence of specific
chemicals (proteins, salts, acids, fats…)
Enteric Nervous System
• A specialized division of the nervous system
associated only with the alimentary canal
• Connected to the CNS via the Parasympathetic NS
(stimulates digestion) and Sympathetic NS (inhibits
digestion)
– Composed of two major nerve plexuses (groups)
which send both sensory and motor information
throughout the alimentary canal to control digestion
• Submucosal nerve plexus (submucosa layer)
–associated with mechano- and
chemoreceptors in the mucosa
–controls the endo- and exocrine secretion of
the mucosa
• Myenteric nerve plexus (muscularis layer)
–controls the contraction of smooth muscle
Chemical Digestion
• Chemical digestion occurs by the action of powerful
enzymes that are either secreted into the lumen or are
integral proteins of the mucosal epithelium hydrolyze
complex macromolecules into molecules small enough
to be absorbable
• Occurs in the mouth, stomach and small intestine
Motility
Contraction of the muscularis causes motility in 2 ways
• Peristalsis is characterized by progressive waves of
contraction that move from one section to the next
– moves food between 2 and 25 cm/sec
– occurs over long distances in esophagus to move
food from the pharynx to the stomach and within the
stomach where it contributes to the mixing of food
– occurs over short distances in the small intestine
• Segmentation is characterized by short segments of
the small and large intestines alternately contracting
and relaxing which mixes contents and keeps them in
contact with absorptive epithelium
Secretion and Absorption
• Exocrine (epithelial) cells of the salivary glands,
pancreas and liver as well as the GI mucosal cells
secrete as much as 7 liters of enzymes, mucus,
electrolytes and water into the lumen daily
• Occurs in all segments from the mouth to the rectum
• The 7 liters of fluid secreted daily into the lumen of the
GI tract must be absorbed to prevent dehydration
– excessive vomiting or diarrhea can be dangerous
• In addition, an average human ingests 2 liters of food
and fluid daily that also needs to be absorbed
• By the time the food and secretions reach the rectum
~98.9% will be absorbed and moved into the body
leaving 100 mL of fluid to be defecated
• Occurs in the small and large intestines
3 Stages of Digestion
• The processes of digestion, secretion, motility and
absorption take place throughout the entire length of
the GI tract in 3 overlapping stages named by the
location of food
– Cephalic (head) phase
• thinking about, smelling, or seeing food which
has not entered the alimentary canal
• food is in the mouth
– Gastric phase
• food is in the stomach
– Intestinal phase
• food is in the small intestine
Cephalic phase
• This phase prepares the digestive system before the
ingestion of food which significantly decreases the
time required for digestion and absorption
• Anticipatory stimuli as well as the presence of food in
the mouth activate Parasympathetic Nervous System
(PNS) controlled reflexes coordinated by the medulla
oblongata
• Action potentials from the medulla are sent to the
stomach, small and large intestines to increase the
secretion of the mucosal cells as well as stimulate the
contraction of the muscularis to move the previously
consumed food distally towards the rectum
• In addition, action potentials are sent to the salivary
glands, and the pancreas to stimulate secretion of
saliva and pancreatic juice, respectively
Composition and Functions of Saliva
• Water
• Ions
• Hydrolytic enzymes
– salivary amylase
• begins the chemical digestion of carbohydrates
– lingual lipase
• begins the chemical digestion of lipids
• Mucin
– protein that aids in the lubrication of a bolus
• ball of chewed food and saliva that is swallowed
• Lysozyme
– antibacterial enzyme that reduces the risk of
infections
Swallowing (Deglutition)
• The tongue forces the bolus into the pharynx causing
the epiglottis to fold over the opening to the airways
(glottis) and diverts the bolus into the esophagus
• The tonically contracted upper esophageal sphincter
which keeps the proximal esophagus closed, relaxes
and opens momentarily while breathing is inhibited
• Once the bolus enters the esophagus, a strong
peristaltic wave pushes the bolus to the stomach
• At distal end of the esophagus, the tonically
contracted lower esophageal sphincter (cardiac
sphincter) momentarily relaxes and opens
momentarily to allow the bolus to enter the stomach
– if the cardiac sphincter does not close properly,
gastric juice containing acid can enter the
esophagus causing painful irritatation (heart burn)
Gastric Phase
• As food enters the stomach, the gastric phase of
digestion begins
• The cephalic phase continues until the food has been
completely ingested and swallowed
• The presence of food in the stomach detected by
mechanoreceptors and chemoreceptors stimulates the
secretion of gastric juice from the gastric mucosa into
the lumen of the stomach to further hydrolyze ingested
food
• The presence of food in the stomach detected by
mechanoreceptors and chemoreceptors also
stimulates the contraction of the muscularis which
mixes the food with gastric juice making a soupy
mixture called chyme
Gross Anatomy of the
Stomach
• The stomach is
divided into the 3
regions: the fundus,
the body and the
antrum and is able to
hold up to 2 liters of
food and fluid when
completely filled
• When the stomach is empty, the
mucosa folds into rugae
– when filled, the expanded wall
of the stomach causes these
folds to disappear (flatten)
The Stomach Wall
• Tubular invaginations (depressions) of the surface
epithelium called gastric glands extend down into the
supporting connective tissue
• Chief cells and parietal cells of gastric glands secrete
substances into the lumen of the stomach which
combine to make gastric juice
Gastric Juice
• Chief cells
– secrete the inactive enzyme (zymogen) pepsinogen
• Begins the chemical hydrolysis of proteins
when pepsinogen is converted to pepsin (active)
– secrete gastric lipase
• continues the chemical hydrolysis of lipids
• Parietal cells
– secrete HCl (hydrochloric acid) to lower pH to 2.0
(optimal for chemical digestion in the stomach)
• denatures swallowed proteins, kills bacteria and
activates pepsin
– secrete intrinsic factor which forms complexes with
vitamin B12 and is essential for its absorption in the
intestine
• lack of intrinsic factor results in pernicious
anemia which is a reduction of red blood cell
synthesis due to a vitamin B12 deficiency
Protection of the Stomach Mucosa
• Mucous cells
secrete a
combination of
mucus (superficial
physical barrier) and
bicarbonate
(chemical buffer
barrier under
mucus) to protect
the mucosa from
autodigestion by
HCl
Hormonal Control of Gastric Function
• The food that enters the stomach dilutes the HCl
component of gastric juice which causes the pH to
increase above 2
– in response, (G cells) of the gastric glands secrete
the hormone gastrin
• gastrin stimulates the parietal cells to secrete
additional HCl to return the pH to 2
• During the intestinal phase (while food is slowly
leaving the stomach), the intestinal hormones secretin
and cholecystokinin (CCK) inhibit HCl secretion from
parietal cells and inhibit the muscularis of the stomach
thus limiting the rate of acidic chyme movement into
the small intestine
Gastric Motility
• As food particles are reduced to a more uniform
texture, each peristaltic wave forces a contracted
pyloric sphincter open which allows only a small
amount of chyme to move into the small intestine
Small Intestine – 3 Segments
• The 3 segments of the small intestine include: the
duodenum (proximal 25 cm), the jejunum (middle
250 cm) and the ileum (distal 360 cm)
• Here digestion is completed by intestinal enzymes
aided by the secretions of the liver and pancreas
– hepatic and pancreatic secretions (bile and
pancreatic juice) enter the lumen of the small
intestine at the duodenum through a duct which is
guarded by the contracted sphincter of Oddi to
keep these fluids from entering the small intestine
except during the intestinal phase of digestion
• The presence of food in the small intestine detected
by mechanoreceptors stimulates a combination of
segmental and peristaltic contractions which mixes the
chyme with pancreatic juice and bile and moves it
toward the large intestine
Small Intestine
Pancreas
A triangular gland located
behind the stomach which
has both exocrine and
endocrine functions
• Acinar (epithelial) cells
secrete pancreatic juice
into a duct that empties
through the sphincter of
Oddi at the duodenum
• Pancreatic islets (islets of
Langerhans) secrete the
hormones insulin and
glucagon to control blood
glucose levels
Pancreatic Juice
• Acinar cells exocytose pancreatic juice into the
pancreatic duct which flows into the duodenum
• Pancreatic juice contains:
• pancreatic amylase hydrolyzes carbohydrates
• pancreatic proteases hydrolyze proteins
–secreted as zymogens
• pancreatic lipase hydrolyzes lipids
• pancreatic nucleases hydrolyze nucleic acids
– bicarbonate (HCO3-)
• a buffer secreted by duct cells that neutralizes
the gastric acid, raising the pH to 8.0 (optimal for
both pancreatic and intestinal enzymes)
Pancreatic Zymogens
• The pancreatic zymogens include:
– trypsinogen
– chymotrypsinogen
– procarboxypeptidase
• The zymogens are converted to their active form by a
series of biochemical reactions initially catalyzed by
the duodenal brush-border enzyme enterokinase
– enzymatically hydrolyzes trypsinogen to trypsin
• trypsin then activates the other 2 zymogens
–chymotrypsinogen to chymotrypsin
–procarboxypeptidase to carboxypeptidase
Activation of Pancreatic Zymogens
Liver and Gallbladder
• Hepatocytes of the liver secrete bile into the hepatic
ducts leading to the gallbladder
• composed of bile acids and phospholipids
• a detergent which causes fat emulsification
–increases the surface area of fat globules
• increases of lipid hydrolysis by lipase
• Gallbladder
– a muscular sac that stores bile secreted from the
liver when the sphincter of Oddi is closed
Hormonal Control of Intestinal Phase
• The presence of acidic chyme in the small intestine
causes the secretion of the intestinal hormone secretin
– stimulates the secretion of pancreatic bicarbonate
• The presence of fatty acids and peptides in the chyme
in the small intestine causes the secretion of the
intestinal hormone CCK
– stimulates the secretion of pancreatic enzymes
– stimulates the contraction of the gallbladder to
squeeze the bile into the bile duct
– relaxes (opens) the sphincter of Oddi, allowing the
entry of pancreatic juice and bile into duodenum
• Both secretin and CCK inhibit HCl secretion from
parietal cells and inhibit the muscularis of the stomach
thus limiting the rate of acidic chyme movement into
the small intestine
pH < 8
fats and
proteins
CCK
causes
relaxation
distension
small Intestine
stimulates
contraction
Sphincter
of Oddi
bile and pancreatic
juice flows into
duodenum
stimulates
enzyme
secretion
Gallbladder
expel
bile
secretin inhibits
peristalsis
and HCl
secretion
stimulates
HCO3secretion
Stomach
slow
gastric
emptying
stimulates
muscularis
Small Intestine
Pancreas
increase pH in
chemically
the small intestine
digest
chyme
segmentation
and peristalsis
Small Intestinal Mucosa
Structural modifications of the mucosa increase the
amount of surface area for digestion and absorption
• When the small intestine is empty, the mucosa is
folded into structures called plicae or circular folds
– when filled, the expanded wall of the small intestine
causes these folds to disappear (flatten)
• Intestinal mucosa also projects into the lumen in small
fingerlike structures called villi
• Tubular invaginations (depressions) of the surface
epithelium that extend down into the supporting
connective tissue of the small intestine are called
crypts
Sectional View of Small Intestine
• Individual epithelial cells of
the small intestinal mucosa
have a highly folded apical
cell membrane
– each fold is called a
microvilli and increase
the number of integral
membrane proteins for
digestion (enzymes) and
absorption (transporters)
that can be exposed to
the lumen
– aka the brush border for
its bristle-like
appearance
Summary of Chemical Digestion in the GI Tract
• Carbohydrates
– salivary amylase (minor) in the mouth
– pancreatic amylase (major) in the small intestine
• Proteins
– pepsin (minor) in the stomach
– pancreatic proteases (major) in the small intestine
• Lipids
– lingual lipase (minor) in the mouth
– gastric lipase (minor) in the stomach
– pancreatic lipase (major) in the small intestine
• bile significantly increases the rate of hydrolysis
• Nucleic acids
– pancreatic nucleases (deoxyribonucleases and
ribonucleases) in the small intestine
• Brush-border enzymes of the small intestine complete
the final hydrolysis of carbohydrates, proteins and
nucleotides prior to their absorption
Absorption of Polar Substances
• Absorption begins as the molecules cross the apical
cell membrane of an absorptive cell of a villus and
diffuse to the basal side of the cell
• Absorption is completed as the molecules cross the
basal cell membrane of an absorptive cell and is
moved into a blood vessel (polar molecules) or a
lymph lacteal (nonpolar molecules) in the submucosa
of a villus
• Most polar molecules (amino acids, nucleotides,
monosaccharides) cross the apical cell membrane by
secondary active transport, using the Na+ gradient
generated by the Na+, K+-ATPase across the cell
membrane
• 95% of ingested and secreted (salivary, gastric,
pancreatic, hepatic, and intestinal) water is absorbed
in the small intestines by osmosis
– molecules of water follow the absorption of solute
molecules through aquaporins
Absorption of Nonpolar Substances
• Following the digestion of triglycerides, the fatty acids
and monoglycerides assemble with cholesterol, lipid
soluble vitamins and bile into a micelle
• The nonpolar micelle diffuses across the apical cell
membrane of the absorptive cell into the Golgi
apparatus
• Once inside Golgi apparatus, the lipids are “packaged”
with proteins (required for transport around the body)
forming a chylomicron
• The chylomicrons are packed into vesicles that are
exocytosed out of the basal membrane
• Chylomicrons, which are too large to enter a blood
vessel, enter lymph lacteals which are large enough to
accommodate the entry of chylomicrons
Distribution of Absorbed Substances
• The polar molecules are absorbed into the blood
vessels flow directly to the liver via the hepatic portal
vein
– connects the blood supply of the gastrointestinal
system and liver
– The liver uptake (transport) some of the nutrients
into the hepatocytes (liver cells) to store a portion of
the absorbed nutrients, the remainder is distributed
to all other cells of the body
• Chylomicrons move through lymphatic vessels until
these vessels merge with the heart where they enter
the circulatory system to be distributed to all cells of
the body
Absorptive and Postabsorptive States
• The absorptive state is the period of time when the
alimentary canal is absorbing nutrients into the body
increasing their levels (most importantly glucose)
• The postabsorptive state is the period of time between
absorptive states (when the alimentary canal is NOT
absorbing nutrients into the body)
– nutrient levels decrease during this time as they are
constantly used
• 2 antagonistic hormones from 2 different cell types of
the pancreatic islets of Langerhans are secreted
during the absorptive or the postabsorptive state in
order to control the levels of circulating glucose (blood
sugar)
– Alpha () cells secrete glucagon
– Beta () cells secrete insulin
Pancreatic Islet
Insulin
• A peptide hormone that is synthesized first in beta
cells as proinsulin (inactive)
– proinsulin is then converted to active insulin in the
Golgi apparatus
• Secreted into circulation during the absorptive state in
response to an increase in the blood glucose level
• Insulin causes a decrease in the blood glucose level
returning it to the set point
– stimulates the uptake of glucose out of the blood
into skeletal muscle cells
– stimulates the uptake of glucose out of the blood
into adipose cells and its subsequent conversion to
glycerol which is stored in adipose as triglycerides
– stimulates the enzymatic conversion of glucose into
glycogen (glycogenesis)
Glucagon
• A peptide hormone that is secreted into circulation
during the postabsorptive state in response to a
decrease in the blood glucose level
• Glucagon causes an increase in the blood glucose
level returning it to the set point
– stimulates lipolysis of triglycerides in adipose cells
and the release of fatty acids into circulation
– stimulates the enzymatic hydrolysis of glycogen
(glycogenolysis) in the liver
– stimulates gluconeogenesis in the liver
• The glucose that is synthesized by the liver is
transported out of the liver into the blood increasing
the blood glucose level
Insulin vs. Glucagon
• Insulin decreases blood glucose levels
– hypersecretion causes hypoglycemia
• low blood sugar
– hyposecretion causes hyperglycemia
• high blood sugar
• can lead to diabetes mellitus
• Glucagon increases blood glucose levels
– hypersecretion causes hyperglycemia
– hyposecretion causes hypoglycemia
Diabetes Mellitus
• A metabolic condition caused by inability of insulin to
function properly
• The 5 symptoms of diabetes mellitus are:
– Hyperglycemia
– Glycosuria
• glucose found in urine
– Polyuria
• large urine output
– Polydipsia
• large thirst
–due to dehydration caused by polyuria
– Polyphagia
• large hunger and food consumption
Diabetes Mellitus
• Type I
– insulin dependent diabetes mellitus (IDDM) or
juvenile onset diabetes
• caused by the loss of insulin synthesis by beta
cells and require insulin injections to control
blood sugar
• Type II
– non-insulin dependent diabetes mellitus (NIDDM)
or adult onset diabetes
• mainly caused by a defect/reduction in the
insulin receptor on target cells
• these individuals produce insulin, therefore
insulin injections are ineffective
• exhibit insulin insensitivity
• The types can be differentially diagnosed in part by a
glucose tolerance test
Large Intestine
• Any food in the small intestine that could not be
chemically digested is moved into the large intestine
where most of the remaining water and ions are
absorbed and the remaining material removed by
defecation
• Subdivided into 3 anatomical segments
– the colon
• ascending colon
• transverse colon
• descending colon
• sigmoid colon
– rectum
– anal canal
Large
Intestine