Download Chapter 5. Digestive system

Chapter 5. Digestive system
I. Introduction
Single-celled organisms can directly take in nutrients from their outside environment.
Multicellular animals, with most of their cells removed from contact directly with the outside
environment, have developed specialized structures for obtaining and breaking down their food.
Animals depend on two processes: feeding and digestion.
Animals are heterotrophs, they must absorb nutrients or ingest food sources. Ingestive eaters,
the majority of animals, use a mouth to ingest food. Absorptive feeders, such as tapeworms, live
in a digestive system of another animal and absorb nutrients from that animal directly through
their body wall. Filter feeders, such as oysters and mussels, collect small organisms and
particles from the surrounding water. Substrate feeders, such as earthworms and termites, eat
the material (dirt or wood) they burrow through. Fluid feeders, such as aphids, pierce the body
of a plant or animal and withdraw fluids.
Cf) Negentropy (Schrödinger)
The Digestive Process is where food becomes less complex (i.e., broken in to its chemical
components) absorbed across the cells of the digestive tract and put into the bloodsteam for
transport throughout the body and to individual body cells.
II. Plans and Locations
The digestive system uses mechanical and chemical methods to break food down into nutrient
molecules that can be absorbed into the blood.
There are two types of plans and two locations of digestion. Sac-like plans are found in many
invertebrates, who have a single opening for food intake and the discharge of wastes.
Vertebrates use the more efficient tube-within-a-tube plan with food entering through one
opening (the mouth) and wastes leaving through another (the anus).
1.
Intracellular digestion: food is taken into cells by phagocytosis with digestive
enzymes being secreted into the phagocytic vesicles; occurs in sponges,
coelenterates and most protozoans.
2.
Extracellular digestion: digestion occurs in the lumen (opening) of the
digestive system, with the nutrient molecules being transferred to the blood or
body fluid; occurs in chordates, annelids, and crustaceans.
III. Stages in the Digestive Process
1. Movement: propels food through the digestive system
2. Secretion : release of digestive juices in response to a specific stimulus
3. Digestion : breakdown of food into molecular components small enough to cross the
plasma membrane
4. Absorption : passage of the molecules into the body's interior and their passage
throughout the body
5. Elimination: removal of undigested food and wastes
Three phases occur during what we loosely refer to as "digestion". Digestion proper, which is
the mechanical and chemical breakdown of food into particles/molecules small enough to pass
into the blood stream. Absorption into the blood stream. Assimilation, the passage of the food
molecules into body cells.
IV. Components of the Digestive System
The digestive system consists of two anatomical
subdivisions: the digestive tract and the accessory
organs.
The human digestive system is a coiled, muscular
tube (6-9 meters long when fully extended)
extending from the mouth to the anus.
Several specialized compartments occur along
this length: mouth, pharynx, esophagus, stomach,
small intestine, large intestine, and anus.
Accessory digestive organs are connected to the
main system by a series of ducts: salivary glands,
parts of the pancreas, and the liver and gall
bladder (bilary system).
1. The Mouth and Pharynx:
Mechanical breakdown begins in the mouth by
chewing (teeth) and actions of the tongue.
Chemical breakdown of starch by production of
salivary amylase from the salivary glands. This
mixture of food and saliva is then pushed into
the pharynx and esophagus. The esophagus is
a muscular tube whose muscular contractions
(peristalsis) propel food to the stomach.
In the mouth, teeth, jaws and the tongue begin
the mechanical breakdown of food into smaller
particles. Most vertebrates, except birds (who
have lost their teeth to a hardened bill), have
teeth for tearing, grinding and chewing food.
The tongue manipulates food during chewing
and swallowing; mammals have tastebuds
clustered on their tongues.

Salivary glands secrete salivary amylase, an
enzyme that begins the breakdown of starch
into glucose. Mucus moistens food and
lubricates the esophagus. Bicarbonate ions in
saliva neutralize the acids in foods. Swallowing
moves food from the mouth through the
pharynx into the esophagus and then to the
stomach.
- Step 1: A mass of chewed, moistened food, a bolus, is moved to the back of the moth by the
tongue. In the pharynx, the bolus triggers an involuntary swallowing reflex that prevents food
from entering the lungs, and directs the bolus into the esophagus.
- Step 2: Muscles in the esophagus propel the bolus by waves of involuntary muscular
contractions (peristalsis) of smooth muscle lining the esophagus.
- Step 3: The bolus passes through the gastroesophogeal sphincter, into the stomach.
Note : Saliva & Salivary Grand
Chemical Composition of Saliva

Water (99%) ,

Proteins (0.3%) and free amino acids (Amylase, Peroxidase, Lysozyme, IgA, IgG,IgM)

Lipids (fatty acids, cholesterol, complex lipids)

Carbohydrates (free glucose and glycosylated proteins and lipids)

Small organic molecules: urea, ammonia, uric acid, steroids, volatile compounds
Ions,
Functions of Saliva

Protective Effect : 1) antibacterial (agglutination, bactericidal, bacteriostatic) 2)antifungal
and antiviral, 3) against physical agents (lubricant, pellicle), 4) against chemical agents
(acid, base) , 5) repair of oral tissues (EGF, NGF), wound licking, 6) buffering agent , 7)
ion reservoir, 8) water balance

Lubrication and binding: the mucus in saliva is extremely effective in binding
masticated food into a slippery bolus that (usually) slides easily through the esophagus
without inflicting damage to the mucosa. Saliva also coats the oral cavity and esophagus,
and food basically never directly touches the epithelial cells of those tissues.

Solubilizes dry food: in order to be tasted, the molecules in food must be solubilized.

Oral hygiene: The oral cavity is almost constantly flushed with saliva, which floats away
food debris and keeps the mouth relatively clean. Flow of saliva diminishes considerably
during sleep, allow populations of bacteria to build up in the mouth -- the result is dragon
breath in the morning. Saliva also contains lysozyme, an enzyme that lyses many
bacteria and prevents overgrowth of oral microbial populations.

Initiates starch digestion: in most species, the serous acinar cells secrete an alphaamylase which can begin to digest dietary starch into maltose. Amylase does not occur in
the saliva of carnivores or cattle.

Evaporative cooling: clearly of importance in dogs, which have very poorly developed
sweat glands - look at a dog panting after a long run and this function will be clear.
Production and Regulation
Saliva is produced by small ("intrinsic") salivary glands
scattered throughout the mouth and by three large, paired,
("extrinsic") salivary glands: the parotid, sublingual, and
submaxillary glands.
Serous cells are primarily responsible for producing a
watery fluid rich in inorganic ions (Ca, P, Na, K, Cl, etc.)
and digestive enzymes. This mixture solvation of food.
Mucous cells produce mucus, a thicker fluid rich in mucin
glycoproteins which help lubricate the oral cavity and ease
swallowing
Both parasympathetic and sympathetic
stimulation increase the rate of saliva
secretion,
however,
parasympathetic
stimulation produces a greater and more
sustained increase. The production of saliva
begins as an isotonic ultrafiltrate of blood, and
consequently, the concentrations of K+,
HCO3-, Na+ and Cl- are similar to plasma. At
high flow rates, the concentration of HCO3- is
higher than that of plasma (pH almost 8)
because most salivary agonists directly
stimulate HCO3- secretion by the salivary
ducts. Saliva has several functions:

lubricates food to facilitate swallowing,

initiates digestion of carbohydrates,

facilitates taste by hydrolysing carbohydrates - taste buds are stimulated

neutralizes any gastric acid that refluxes from stomach

helps to minimize tooth decay
Secretagogues that bind to ß-receptors (i.e. norepinephrine and epinephrine)
stimulate increased production of cAMP. This leads primarily to increased
secretion of amylase. Acetylcholine released from parasympathetic nerve
terminals (neurocrine) binds to receptors that activate phospholipase c, leading
to an increase in intracellular IP3 production. Alpha agonists also stimulate IP3
production, however, this is not a major mechanism for stimulation of salivary
glands. IP3 stimulates release of calcium from intracellular stores resulting in an
increase in intracellular calcium. Increased calcium stimulates both protein
and fluid secretion.
2. The Stomach
1. General Morphology: During a meal, the stomach gradually fills to a capacity of 1 liter,
from an empty capacity of 50-100 milliliters. At a price of discomfort, the stomach can
distend to hold 2 liters or more.
2. Microscopic Morphology : Epithelial cells line inner surface of the stomach, and
secrete about 2 liters of gastric juices per day. Gastric juice contains hydrochloric acid,
pepsinogen, and mucus; ingredients important in digestion. Secretions are controlled
by nervous (smells, thoughts, and caffeine) and endocrine signals. The stomach
secretes hydrochloric acid and pepsin. Hydrochloric acid (HCl) lowers pH of the
stomach so pepsin is activated. Pepsin is an enzyme that controls the hydrolysis of
proteins into peptides. The stomach also mechanically churns the food. Chyme, the mix
of acid and food in the stomach, leaves the stomach and enters the small intestine.
3. Digestive Function
The stomach is a muscular J-shaped enlargement of the GI tract. It functions as a
mechanical breakdown organ where food is liquidified. It is also a site where some
chemical digestion is initiated and specifically directed towards proteins and lipids.
1) Mechanical digestion: The primary anatomical characteristic that aids in
mechanical digestion is the muscle layers of the muscularis externa (the external
muscle layer of the tunic layers of the wall). These muscles allow for random and
organized movements called segmental movements and peristalsis respectively.
Stomach motility. Shortly after food enters the stomach, motility increases. There
are first random muscle contractions that occur throughout the wall of the stomach
to effectively mix and churn the chyme. Later more organized peristaltic
movements begin. These movements "roll" the chyme and push the chyme into the
small intestine when the small intestine is ready to receive new food to digest. It is
the small intestine that directs movement of foods and wastes in the system.
2) Chemical Digestion: The stomach secretes about 2-3L of gastric juice a day. This
is a complex mixture of compounds and acids designed to begin the chemical
digestion of proteins and lipids.
Ingredients of gastric juices:
A)
Hydrochloric Acid. We are probably all aware that gastric juices are
very acidic (pH 1.0). The reactions that produce the hydrochloric acid
are: CO2 + H2O -> H2CO3 -> HCO3- + H+
summary: In this case, the carbon dioxide diffuses into the
mucosal cells of the stomach in the gastric pits - specifically into
the parietal cells from the bloodstream. The parietal cells contain
carbonic anhydrase, the enzyme responsible for the above left
reaction. As bicarbonate ions are produced they diffuse back into
the bloodstream; the hydrogen ions on the other hand, are
pumped (via a potassium/hydrogen ion exchanger) into the lumen
of the stomach. The chloride ions follow from the bloodstream.
There are two consequences to this:
i) lumen of stomach becomes more acidic due to the
accummulation of hydrogen ions and chloride ions.
ii) bloodstream becomes more basic -alkaline tide - due to the
transport of bicarbonate ions back into the bloodstream.
B)
Enzymes. The chief cells located in the gastric pits secrete pepsinogen.
Pepsinogen is an inactive protein-digesting enzyme (generically called a
zymogen) that is converted to an active enzyme in the presence of acid.
Activated Pepsin chops up ingested proteins into smaller proteins. The
other enzymes that the stomach produces are only produced during
infancy and are designed to facilitate milk digestion. Carbohydrate
digestion, begun by salivary amylase in the mouth, continues in the
bolus as it passes to the stomach. The bolus is broken down into acid
chyme in the lower third of the stomach, allowing the stomach's acidity
to inhibit further carbohydrate breakdown. Protein digestion by pepsin
begins. Alcohol and aspirin are absorbed through the stomach lining into
the blood. Epithelial cells secrete mucus that forms a protective barrier
between the cells and the stomach acids. Pepsin is inactivated when it
comes into contact with the mucus. Bicarbonate ions reduce acidity near
the cells lining the stomach. Tight junctions link the epithelial stomachlining cells together, further reducing or preventing stomach acids from
passing.
C)
Intrinsic factor. The parietal cells also secrete this glycoprotein factor
that allows the small intestine to absorb vitamin B12. Vitamin B12 is
essential for hemoglobin production during erythropoiesis.
D)
Chemical Messengers: The stomach produces about 20 chemical
messengers that act as either hormones or paracrine secretions. We will
discuss these in more detail when we examine feedback mechanisms
that control digestion. Gastrin is an example of a hormone produced by
the stomach.
1.
paracrine action is to promote acid secretion by the parietal cells and
pepsinogen secretion from the chief cells.
2.
hormone action is to signal the large intestine to empty since there is
food in the stomach.
4. Regulation of Gastric Secretion
A)
Nervous Regulation : The vagus mediates the Cephalic Phase (both
psychic and gustatory) of gastric secretion. (The cephalic phase may be
studied by sham feeding: i.e. the food is chewed but not swallowed) The
vagus stimulates enteric neurons which are excitatory to the secretory
cells. Neural mechanisms (local enteric reflexes and vago-vagal
reflexes) also participate in the gastric and intestinal phases.
B)
Hormonal Regulation : Antral gastrin mechanism: Gastrin (a
heptadecapeptide) released from the antral mucosa, in the presence of
Secretagogues, Vagal Stimulation, (of enteric neurons) or Distension
(via local or vago-vagal reflexes), is carried in the circulation, and acts
primarily on the parietal cells causing the secretion of HCl.
-
Note that neural activation of the G cell is mediated by NANC neurons releasing
GRP ( Gastrin- Releasing- Peptide).
-
Stimulants to Gastrin release
1) Secretagogues
2) Vagal stimulation
3) Distension (local mech.)
4) Distension (vago-vagal reflex)
5) Gastrin pathway
-
Cycle:
1) Normal gastrin regulating mechanism of HCl
2) HCl levels increased
3) pH<2, gastrin release inhibited
4) HCl levels reduced
5) pH>2, gastrin release resumes
6) Normal conditions reestablished
5. Ulcers
Peptic ulcers result when these protective mechanisms fail. Bleeding ulcers result when tissue
damage is so severe that bleeding occurs into the stomach. Perforated ulcers are lifethreatening situations where a hole has formed in the stomach wall. At least 90% of all peptic
ulcers are caused by Helicobacter pylori. Other factors, including stress and aspirin, can also
produce ulcers.
Helicobacter pylori,
3. The Small Intestine
The small intestine is where final digestion and absorption occur. The small intestine is a coiled
tube over 3 meters long (10 liters of water enter the small intestine). Coils and folding plus villi
give this 3m tube the surface area would be greater that a tennis court!
Final digestion of
proteins and carbohydrates must occur, and fats have not yet been digested. Villi have cells that
produce intestinal enzymes, which complete the digestion of peptides and sugars. The
absorption process also occurs in the small intestine. Food has been broken down into particles
small enough to pass into the small intestine. Sugars and amino acids go into the bloodstream
via capillaries in each villus. Glycerol and fatty acids go into the lymphatic system. Absorption is
an active transport, requiring cellular energy.
1. General Morphology : The small intestine is the longest section of the digestive tube
and consists of three segments forming a passage from the pylorus to the large intestine:
- Duodenum: a short section that receives secretions from the pancreas and
liver via the pancreatic and common bile ducts.
- Jejunum: considered to be roughly 40% of the small gut in man, but closer
to 90% in animals.
- Ileum empties into the large intestine; considered to be about 60% of the
intestine in man, but veterinary anatomists usually refer to it as being only
the short terminal section of the small intestine.
In most animals, the length of the small intestine is roughly 3.5 times body length - your
small intestine. Although precise boundaries between these three segments of bowel are
not observed grossly or microscopically, there are histologic differences among
duodenum, jejunum and ileum.
2. Microscopic Morphology
a. large surface area
b. folded like accordian (promotes spiral flow and mixing)
c.
villi (increases surface area 10X)
d. microvilli ( increase surface area another 600X)
3. Digestive Function
1) Motility of Intestine
a) Mixing - to ensure efficient digestion and absorption
b) Propulsion - sufficiently slow to ensure efficient digestion and absorption
VIP: Vasoactive intestinal peptide, SP: Substance P, ENK: enkephalin, SST:
Somatostatin
2) Chemical Reaction
-
Pancreatic Secretion
Pancreas: a compound acinar gland, similar to the salivary glands - i.e., aciniconstituting 80-90% of the gland - and an elaborate duct system.
(Islets of Langerhans cells responsible for endocrine secretions. Islet
hormones perfuse surrounding acinar cells by the insuloacinar portal
system, and may regulate digestive enzyme synthesis and
transport.)
Pancreatic Juice : 1) 0.5-l.5 L/day 2) pH approx. 8 (due to large HCO3content) 3) Isotonic; Main Electrolytes: Na+, K+, Cl-, HCO3-; 4) high
protein content
HCO3 (Centroacinar/Terminal ductular cell)
(Note that the recycling of Cl- at the luminal surface appears to be
important for sustained HCO3- secretion.)
Enzyme (>80% of all protein found in pancreatic juice)
a)
Amylase
b)
Various proteases are secreted as inactive precursors. Activation
takes place only in the small intestine under the influence of
Enterokinase an intestinal enzyme, released by interaction with bile
acids (and by CCK?), and according to the scheme outlined below.
Trypsin inhibitor - it is important that the proteolytic enzymes of
pancreatic juice not become activated until they have been released
into the intestine, for the trypsin or other proteases would digest the
pancreas itself. Fortunately, the same cells that secrete the
proteases of the pancreas, also secrete a small peptide called
trypsin inhibitor, which binds tightly to trypsin, preventing its action,
both inside the secretory cells and the ducts of the pancreas. Since it
is trypsin that activates the other pancreatic proteases, trypsininhibitor prevents the subsequent activation of all these.
Pancreatic juice also contains RNase, DNase, and Phospholipase
(is secreted as an inactive precursor, activated by trypsin)
c)
Lipases (triglyceride lipase, phospholipase A2, carboxylesterase)
The pancreatic acini also secrete a colipase (small peptide cofactor),
which binds to lipase, facilitates interaction with fat droplets allowing
the enzyme to digest triglycerides and promoting the incorporation of
products into micelles. Colipase is secreted as procolipase, and is
activated by trypsin.
Regulation of Pancreatic Juice Secretion - secretion of pancreatic juice is
largely under the control of hormonal mechanisms, though some
neural regulation also exists.
a)
Neural
- stimulation of the parasympathetic supply to the pancreas
- stimulation of the sympathetic supply to the pancreas ->primarily
vasoconstriction
b)
Hormonal
i)
SECRETIN, released from the duodenal mucosa in the presence of
a low pH (threshold for release is a pH < 4.5), is carried in the
circulation and acts on the pancreas ( through receptors linked to
Vagus Nerve
adenylate cyclase which raises intracellular cAMP levels, activating
cAMP-dependent protein kinase), causing the secretion of a large
ACh
Secreti
CCK
volume of water with a high HCO-3 content.
n
Atropine
ii)
CHOLECYSTOKININ, released from the duodenal mucosa in the
presence of fatty acids and products of protein breakdown, is
carried in the circulation and acts on the pancreas (through
++
Ca
cAMP
++
Ca
phospholipase C, which acts on membrane-bound lipids to release
inositol triphosphate, which releases Ca++ and diacylglycerol which
activates protein kinase C) causing the release of enzyme (small
HCO3–
volume of juice, low in HCO3-). CCK also has a trophic effect on
Secretio
the pancreas. (Note the similarity between the secretion elicited by
Enzymen
Secretion
CCK, and that produced in response to vagal stimulation.)
iii)
GASTRIN, released from the antral mucosa, acts on the pancreas,
causing the release of a moderate volume of water and
bicarbonate, with a moderate amount of enzymes.

Secretin has historical significance: first hormone to be described

The secretin mechanism is a self-regulating one, similar in some respects to the gastrin
mechanism described for the stomach. Try to outline this feedback mechanism.

There is a high degree of interdependence between the neural and the hormonal
mechanisms: Secretin, CCK and ACh potentiate one another's secretory effects (cf. receptor
interaction on parietal cell).
.
Phases of pancreatic juice secretion
a)
Resting (interdigestive) - a small continuous flow, low in enzyme
content; mechanism unknown. Pattern is cyclical, related to MMC.
b) Cephalic (Psychic & Gustatory) - small volume, high enzyme
content; simple or conditioned reflex, via vagus (ACh and NANC).
c) Gastric - small volume, high in enzyme content; a vago-vagal
gastro-pancreatic reflex, initiated by gastric distension. Also through
the release of gastrin
d) Intestinal - large volume of alkaline juice, rich in enzymes;
secretin and CCK mechanisms set up by presence of chyme in the
duodenum; a vago-vagal intestino-pancreatic reflex, initiated by
duodenal distension also plays a role.
* Under certain circumstances, activated pancreatic enzymes are liberated
from the acini into the surrounding tissue, causing destruction of the gland itself
(pancreatitis).
* The dominant effect of pancreatic disease resulting in reduced enzyme output
is steatorrhea (appearance of undigested fat - 60 to 70% of intake - in
feces). Explain.
* Loss of nutrients due to insufficient pancreatic output can be partly corrected
by oral administration of pancreatic enzyme preparations. What problems must
be overcome?
* Consider the effects on the digestive tract, and on digestion itself, resulting
from loss of the bicarbonate component of pancreatic juice.
-
Liver & Gall Bladder Secretion
1. Liver Function Organization
a)
The liver secretes bile continuously.
b)
The flow of bile into the duodenum is intermittent.
c)
In interdigestive periods, bile is diverted to the gall bladder, where it
undergoes
i)
concentration (l0x) of solids
ii)
acidification
iii)
increase in viscosity
2. Characteristics of Liver Bile
a)
0.5-l.0 L/day
b)
pH 7.8-8.6 (cf. gall bladder bile pH 7.6)
c)
isotonic; main electrolytes: Na+, K+, HCO3-,Cl-.
d)
Biliary Solids: bile salts, bile pigments, cholesterol, phospholipids.
3. Mechanism of Secretion
Bile may be considered to be an admixture of three secretions:
a)
Bile acid-dependent bile formation accounts for ~ 50% of
canalicular bile flow. Bile acids are efficiently extracted from portal
blood and actively transported into the hepatocyte by a Na+ coupled
mechanism (which in turn depends on the electrochemical Na+
gradient maintained by a Na+ /K+ ATPase in the sinusoidal lateral
membranes). A poorly understood carrier mediated, rate limiting
mechanism for bile acid transport across the canalicular membrane
has also been proposed.
b)
Bile acid-independent bile formation (less important in humans)
results from the active transport of Cl- by membrane carriers into the
biliary canaliculi, where negative charges on the tight junctions
prevent anion back- diffusion. Cations such as Na+ pass passively
across the tight junctions into the canaliculi followed by water flowing
through or between the liver cells. Currently, a mechanism for active
HCO-3 secretion across the canalicular membane is also considered
to play an important role.
c)
Ductular fluid very likely also depends on active HCO-3 secretion.
4. Composition of Bile
In the interdigestive period, most bile is diverted into the gall
bladder, from where ions and water are reabsorbed, resulting in
the concentration of solids. The ionic composition of plasma,
hepatic bile and gall bladder bile are illustrated. The bile samples
are isotonic with plasma, even though the total number of anions
and cations is greater, as indicated by the dashed line. The
explanation is that with concentration, the solids are progressively
incorporated into macromolecular complexes (micelles), where
they exert little osmotic effect. Concentration of bile in the gall
bladder can be explained by absorption of an isotonic solution of
NaCl (and NaHCO3), leaving what is essentially a concentrated
but isotonic solution of sodium bile salts.
5. Scheme Showing Fluid Transport in Gall Bladder
Ions are transported via transcellular and paracellular pathways into
lateral intercellular spaces, where a "standing osmotic gradient" is
established for the passive absorption of water, which elevates the
hydrostatic pressure and promotes entry into the capillaries.
6. Enterohepatic Circulation of Bile Salts
Note Bile Salt
Bile salts are formed in the hepatocytes by a series of
enzymatic steps that convert cholesterol to cholic or
chenodeoxycholic (CDC) acids. The rate limiting step is
hydroxylation at the 7-alpha position. These acids are then
conjugated with glycine or taurine, and secreted as Na +
(or K + ) salts. Conjugation causes a decrease in their pKa
values, making them more water-soluble.
The formation of bile salts is the main excretory pathway
for cholesterol from the body.
They are amphipaths, with both hydrophilic and lipophilic regions, which - above a critical
concentration - aggregate to form micelles, which serve to "solubilize" and transport fat- soluble
substances. They reduce surface tension and stabilize emulsions; they also activate lipase.
More than 90% of the bile salts are actively reabsorbed (by a
sodium-dependent cotransport process) from the ileum into the
portal blood from where they are cleared (by a receptor- mediated
process) and resecreted by the liver. This secretion-reabsorption
cycle is called the ENTEROHEPATIC CIRCULATION. An additional
small amount of bile salts are dehydroxylated (and deconjugated) by
colonic bacteria to form secondary bile salts which are also
reabsorbed (passively), returned to the liver, (reconjugated) and
resecreted. The enterohepatic cycling of bile salts increases during
digestion and slows down between meals and during overnight
fasting.The entire bile salt pool consists of 2-4g of bile salts, and can
recirculate 2-3X with each meal.
Normally, hepatic bile contains about 80% primary and 20%
secondary bile salts.
a)
Primary bile acids formed in the liver from cholesterol.
b)
Secondary bile acids formed by colon bacteria from primary
bile acids (by dehydroxylation).
Bacteria also deconjugate bile salts. Deconjugated bile salts are
less effective, since they are more lipophilic (and thus more likely to
be passively absorbed prematurely in the proximal small intestine);
as well, at the luminal pH, they are less resistant to precipitation or
formation of insoluble calcium salts.
7. Bile Salt Functions
a)
Intraportal : High concentrations of bile salts in the portal blood
have a positive effect on the volume of bile secreted by the liver (as
they are resecreted into the canaliculi, they create an osmotic
gradient causing the output of a larger volume of fluid), but a
negative effect on the synthesis of new bile salts by the liver (by
inhibiting the hepatic cholesterol 7-alpha hydroxylase; when their
portal concentration is low, the enzyme is derepressed). Thus,
removing the distal ileum decreases the rate of return of bile salts in
the portal blood, resulting in a much greater rate of de novo bile-salt
synthesis. Orally administered, bile salts cause an increase in the
levels of bile salts in portal blood, and a greater degree of inhibition
of bile-salt synthesis.
b)
Intrahepatic: "solubilize" biliary cholesterol
CHOLESTEROL: insoluble in water, but soluble in bile where it
dissolves in the interior of micelles of bile salts and lecithin.
PHOSPHOLIPIDS: primarily lecithin; amphipaths, whose solubility is
enhanced by bile salts. The combination of bile salts and lecithin is
better able to solubilize cholesterol.
c)
Intestinal : The intestinal functions of bile salts include the following:
1) help form stable emulsions
2) activate pancreatic enzymes
3) assist in the transport across the "unstirred layer" and
absorption of fat and fat soluble vitamins.
4) antibacterial?
In the intestine, the secretions from the pancreas, intestine and
stomach dilute the concentrated bile delivered from the gall bladder.
This, in turn, dilutes the unaggregated bile salt conjugates, resulting
in rearrangement of the lipid containing micelles into polymolecular
disks. The products of hydrolysis of dietary triglycerides become
incorporated into these polymolecular disks, along with the fat
soluble vitamins
d)
Colonic
In the colon, bile salts inhibit Na+ transport and water
absorption. BILE PIGMENTS: Bilirubin and biliverdin are endproducts of hemoglobin breakdown, excreted by the liver in the bile
and lost in the feces.
1.
Intestinal Secretion
Structural and Functional Organization of Secretory Elements
a)
Brunner's Glands: restricted to the upper duodenum; branched, coiled
tubules, extending into the submucosa, secrete an alkaline juice rich in
mucin, devoid of enzymes. They respond to secretin and to vagal
stimulation.
b)
Crypts of Lieberkühn: located throughout the small intestine, they
produce a secretion which is alkaline (pH 7-9) and isotonic. Although it is
usually stated that about 2-3 L of intestinal juices ("succus entericus") are
secreted, the exact volume is difficult to estimate because of the very
large bidirectional fluxes of water and ions (secretion into/absorption out
of the lumen) that occur in the organ. This secretion is largely the result of
anion transport across the apical membrane into the lumen, as illustrated
below.
c)
Villus enterocytes:. amylase, enterokinase, lipase, peptidases,
disaccharases.
2.
Mechanism of Fluid Secretion of Crypt Cells
Cl- enters the cell across the basolateral membrane via a coupled
Na+/Cl- (actually Na+/K+/2Cl)- transport process maintained by Na+
extrusion across the basolateral membrane by Na+/K+ ATPase
activity. cAMP and intracellular Ca++ increase Cl- permeability of the
apical membrane favoring Cl- secretion into the lumen.
*cAMP also inhibits neutral Na+/Cl- absorption (see later).
Some secretion may also be driven by an active secretion of HCO3-.
3.
REGULATION OF SECRETION The regulation of the enterocytes is based on
local, mechanical or chemical stimulation of the mucosa by the chyme
present..Mucosal endocrine cells probably regulate intestinal transport
functions in a largely paracrine fashion. There is evidence, as well, that there
is immune regulation of intestinal transport: intestinal immune cells release an
array of secretory factors which may act directly on the epithelial cells or
indirectly by stimulating the release of such agents as acetylcholine or
prostaglandins.
4.
THE LARGE INTESTINE - Secretion
A small volume of alkaline, K+-rich, mucus-rich secretion is released by the
colon. No digestive enzymes are secreted by the colon, but there is significant
bacterial activity.
The epithelial cells of the small intestine turn over in a rapid,
continuous and coordinated way. As the mature cells are shed into
the intestinal lumen, epithelial integrity is maintained as adjacent
cells appear to extend cell processes underneath the extruded cell to
link with each other, thus forming new junctional complexes.
3)
Absorption :Each villus has a surface that is adjacent to the inside of the
small intestinal opening covered in microvilli that form on top of an epithelial cell
known as a brush border. Each villus has a capillary network supplied by a small
arteriole. Absorbed substances pass through the brush border into the capillary,
usually by passive transport. Maltose, sucrose, and lactose are the main
carbohydrates present in the small intestine; they are absorbed by the microvilli.
Starch is broken down into two-glucose units (maltose) elsewhere. Enzymes in
the cells convert these disaccharides into monosaccharides that then leave the
cell and enter the capillary. Lactose intolerance results from the genetic lack of
the enzyme lactase produced by the intestinal cells. Peptide fragments and
amino acids cross the epithelial cell membranes by active transport. Inside the
cell they are broken into amino acids that then enter the capillary. Gluten
enteropathy is the inability to absorb gluten, a protein found in wheat. Digested
fats are not very soluble. Bile salts surround fats to form micelles that can pass
into the epithelial cells. The bile salts return to the lumen to repeat the process.
Fat digestion is usually completed by the time the food reaches the ileum (lower
third) of the small intestine. Bile salts are in turn absorbed in the ileum and are
recycled by the liver and gall bladder. Fats pass from the epithelial cells to the
small lymph vessel that also runs through the villus.
4. Large Intestine
Gross structure: cecum, ascending colon, transverse colon, descending colon, sigmoid colon,
rectum.
Gross modification in muscular elements: over the greater part of the
large intestine, the longitudinal muscle is incomplete, forming the teniae
coli. It becomes complete in the sigmoid colon, and remains so in the
rectum.
The myenteric plexus is concentrated underneath the teniae, and
receives input from local receptors, as well as from the two divisions of
the ANS.
Functional Requirements
A)
Mixing (to promote fluid and electrolyte absorption) - rings of circular muscle contract
rhythmically (irregularly and sluggishly) dividing the colon into large sacs or HAUSTRA. Slow
propulsion is also achieved by these movements.(Remember that segmenting activity also gives
rise to some resistance and in the distal colon it offers resistance, thereby retarding caudad
movement).
B)
Storage- temporary storage of semiliquid chyme allowing it to become semisolid feces.
C)
Propulsion - 3-4 times a day, usually after meals, the colonic contents are moved into the
rectum by long peristaltic rushes or MASS MOVEMENTS and involve long reflexes
( gastrocolic, and ileocolic reflexes).
Regulation
Colonic activity is governed by a BER (ECA) which is highly variable and exhibiting a higher
frequency in some of the distal parts than in the more proximal portion. Thus the motor activity
of the colon lacks the pattern of uniform aborad propagation characterizing the stomach and the
small intestine. At least two types of spike activity seem to exist in the colon: ERA superimposed
on the BER (ECA) waves and initiative of more localized and bidirectional contractions, and
clusters of spike bursts which are unrelated to the BER (ECA), but which migrate distally
towards the sigmoid and rectum; the latter are believed to be more closely associated with the
periodic mass propulsion of luminal contents. Enteric nerves exert an important influence with
the major effect being inhibitory (VIP?): destruction of the ENS results in tonic contraction, and
loss of coordinated movements. The ANS and gut hormones play a modulating role.
Transit Time in the Small Intestine & Colon
The first part of a test meal reaches the cecum in about 4 hours, and all of the undigested
portions have entered the colon in 8 or 9 hours. In the average, the first remnants of the meal
reach the transverse colon in 6 hours, the descending colon in 9 hours, and the sigmoid colon in
12 hours. From the sigmoid colon to the anus, transport is much slower. As much as 25% of
the residue of a test meal may still be in the rectum in 72 hours. When small colored beads are
fed with a meal, an average of 70% of them are recovered in the stool in 72 hours; but total
recovery requires more than a week.
Defecation
Defecation involves both reflexes and voluntary actions. The reflex activities are integrated in
the sacral spinal cord, but are influenced by higher centres. Delivery of the feces to the sigmoid
stretches the wall and initiates peristaltic activity propelling the feces to the rectum whose upper
portion relaxes to permit entry of the load. Rectal distension relaxes the internal anal sphincter
(via intrinsic reflex) but - initially - causes contraction of the external sphincter via an extrinsic
somatic reflex re-inforced voluntarily. The internal sphincter regains its tone, and the urge to
defecate subsides. The above is repeated until the rectal stretch signalled to the cerebral
cortex to make the individual aware of the forthcoming event takes place under socially
acceptable circumstances. The seated or squatting position is assumed which provides
mechanical advantage to the abdomen against which the thighs are abutted. Usually, the
person inhales, closes the glottis and exhales, thus raising intrathoracic pressure
considerably. (This "Valsalva maneuver" can stop venous return and lead to cardiac arrest,
especially in the elderly.) This increase in pressure is transmitted to the peritoneal space and
impinges on the serosal surfaces of the sigmoid and rectum. Simultaneously, the person
contracts the anterior abdominal muscles and further increases pressure within the abdominal
cavity squeezing the outside of the viscus holding the feces. The internal anal sphincter
relaxes in response to NANC nerve stimulation triggered by stretch of the rectum. Cholinergic
impulses also stimulate peristalsis and cause extensive longitudinal muscle contraction, thereby
shortening the organ. Due to the body position, the gluteal muscles stretch the external anal
orifice. At this time the individual voluntarily relaxes the external anal sphincter.
Continence
Continence is normally maintained by an interaction of several factors:
i)
Normal transit of a normal consistency stool
ii)
Normal capacity rectum to provide an adequate reservoir
iii)
Normal voluntary control and normal reflex function provided by the anal sphincter
complex
Overview
Gastrointestinal Functional Activities: Three major functional activities may be identified:
1.
Motility
2.
Secretion
3.
Absorption
GASTROINTESTINAL NEURAL REGULATION
Neural regulation involves both intramural reflexes, mediated by the plexuses of the wall
(the Enteric Nervous System - ENS - or " Intrinsic Innervation") and central influences,
mediated by parasympathetic and sympathetic fibres that reach the wall of the tract (the "
Extrinsic Innervation").
HORMONAL REGULATION
A number of gastrointestinal hormones (peptide in nature) are released
from endocrine cells (" Diffuse Endocrine System - DES) dispersed in the
mucosa of the stomach and small intestine by nervous stimulation,
distention and luminal chemical (e.g. hydrolytic products of food)
stimulation, coincident with the intake and transport of food.