OPTION D HUMAN PHYSIOLOGY

D.2 DIGESTION
D.2.1 Nervous and hormonal mechanisms control the secretion of
digestive juices

THE NERVES AND DIGESTION - conceptual base

The digestive system is under control of the Autonomic Nervous System (ANS).
The ANS controls body process that are not under our conscious control. This
means that when we eat food, we don't need to think about how our body will
digest it. The Autonomic Nervous System automatically does what needs to be
done. The digestive system is also controlled by hormones released by glands in
the body.
The Autonomic Nervous System includes the Sympathetic Nervous System
(SNS) and the Parasympathetic Nervous System (PNS). The SNS is
responsible for the Flight or Fight response of the body. When we get scared, the
SNS increases our heart rate and provides energy to our muscles in preparation for
action. In order to provide more energy to the heart, lungs and muscle, it inhibits
(slows or stops) digestion by directing blood flow away from the digestive tract.
The PNS is responsible for stimulating digestion by increasing blood flow to the
digestive tract. The PNS stimulates salivary gland secretion and increases
peristalsis. This increases the digestion of food and absorption of nutrients.
The ANS controls digestive functions such as:
secretion of saliva from the salivary glands
peristalsis to move food along the digestive tract
gastric acid production in the stomach
sphincter open and closing
hormone release from glands in the digestive system
the storing energy in the form of fat.
Two types of nerves help control the action of the digestive system:
1. Extrinsic nerves, controlled by the brain, cause muscle contractions that
push food along the digestive tract. They also cause the stomach and
pancreas to produce more digestive juice.
2. Intrinsic nerves within the walls of the oesophagus, stomach, small
intestine, and large intestine react when their walls are stretched by food.
They cause the release of substances that speed up or slow down the
movement of food, and the production of juices, by the digestive organs.

DIGESTIVE PHASES
The response to food begins even before food enters the mouth.

The first phase of ingestion, called the cephalic phase, is controlled by the neural
response in the ANS to the stimulus provided by food. All aspects, such as sight,
sense, and smell, trigger the neural responses resulting in the stimulation of the
exocrine gland cells, resulting in salivation and secretion of gastric juices. The
gastric and salivary secretion in the cephalic phase can also take place at the
thought of food. Right now, if you think about a piece of chocolate or a crispy
potato chip, the increase in salivation is a cephalic phase response to the thought.
The central nervous system prepares the stomach to receive food.
The gastric phase begins once the food arrives in the stomach. It builds on the
stimulation provided during the cephalic phase. Gastric acids and enzymes process
the ingested materials. The gastric phase is stimulated by:
(1) distension of the stomach
(2) a decrease in the pH of the gastric contents
(3) the presence of undigested material.
This phase consists of local, hormonal, and neural responses. These responses
stimulate secretions and powerful contractions.
The intestinal phase begins when chyme enters the small intestine, triggering
digestive secretions. This phase controls the rate of gastric emptying. In addition
to gastric emptying, when chyme enters the small intestine, it triggers other
hormonal and neural events that coordinate the activities of the intestinal tract,
pancreas, liver, and gallbladder.

D.2.2 Exocrine glands secrete to the surface of the body or the

lumen of the gut.

Define alimentary canal:

The tubular passage from mouth to anus which functions in digestion and absorption of
food, and elimination of residual waste.

Recognise the principal organs and tissues of the human alimentary canal.

What can you label?

Understand the structure of the stomach wall.

Contrast and compare endocrine glands with exocrine glands, and hormones
with enzymes.
Label a diagram of an exocrine gland with the following terms: secretory cells,
lumen, duct, secretory vesicles, basement membrane and acinus. (Pancreas)

Identify electron micrographs of exocrine gland cells (in pancreas) and discuss
the relationship between the structures of an exocrine gland cell and the
function of the cell. Include: nucleoli, RER, Golgi apparatus, large vesicales,
mitochondria.
Label up the diagram:

State the name and location of three exocrine glands associated with the
alimentary canal.
State the composition of saliva, gastric juice and pancreatic juice.
Saliva is a watery substance located in the mouths of humans and
animals, secreted by the salivary glands. Human saliva is 99.5% water, while the other
0.5% consists of electrolytes, mucus, glycoproteins, enzymes, and antimicrobial agents
such as secretory IgA and lysozyme.
Gastric Juice is a fluid secreted into the stomach. It is a mixture of secretions from
gastric glands and epithelial cells. Other components are salt, water, HCl, pepsin,
intrinsic factor, and mucus.
Pancreatic juice is a liquid secreted by the pancreas, which contains a variety of
enzymes, including trypsinogen, chymotrypsinogen,elastase, carboxypeptidase,
pancreatic lipase, nucleases and amylase. (NB: Insulin and glucagon are of course
hormones secreted into the blood from the pancreas and are therefore NOT part of
pancreatic juice.)

D.2.3 The volume and content of gastric secretions are controlled

by nervous and hormonal mechanisms.
Using a flow chart or concept map, diagram the interactions between
nervous and hormonal mechanisms that regulate the secretion of gastric
juices. (Link D.2.1 and D.2.2)

D.2.4 Acid conditions in the stomach favour some hydrolysis

reactions and help to control pathogens in ingested food.
H+ and Cl- are secreted separately by parietal cells in the stomach wall. The resultant acid
conditions provided by HCl (~pH 2-3):
Enable some hydrolysis reactions
Activates pepsinogen, which becomes pepsin
Provide optimum conditions for the enzyme pepsin
Denature some proteins, so making it easier for proteases to break peptide links
Kill some bacteria.

D.2.5 The structure of cells of the epithelium of the villi is

adapted to the absorption of food.
Outline the role of the following structures of villi epithelial cells: tight
junctions, microvilli (brush border), mitochondria, pinocytic vesicles,
proteins imbedded on the apical (mucosal) surface and proteins imbedded
on the basal surface.
This is a useful powerpoint to work from:
http://www.cpanel.stpaulsscience.org/uploaddata/117/NEW%20SPEC.
%20AS1/7.Ileum/15.6%20Digestion%20Part2.ppt

This account is very detailed but if this is the way you want to go, then .....
http://www.ncbi.nlm.nih.gov/books/NBK21502/

D.2.6 The rate of transit of materials through the large intestine

is positively correlated with their fibre content.
Define dietary fibre.
Dietary fiber or roughage is the indigestible portion of food derived from plants. It has
two main components:

Soluble fibre, which dissolves in water, is readily fermented in the colon into gases
and physiologically active byproducts, and can be prebiotic and viscous.
Insoluble fibre, which does not dissolve in water, is metabolically inert and provides
bulking, or it can be prebiotic and metabolically ferment in the large intestine. Bulking
fibres absorb water as they move through the digestive system, easing defecation.

List benefits of fibre in a healthy diet:

Fermentation - consumed by microbiota with many, far-reaching benefits, including

gene expression, immune system benefits, glucose and lipid metabolism,
prevention of inflammation, etc
Viscosity - reduction in sugar and lipid absorption, positive effect upon blood
glucose response after meals
Bulking - absorption of water and regular passage of faecal matter through the
colon

State the relationship between food fibre contents and rate of transit
through the large intestine.

D.2.7 Materials not absorbed are egested.

Define egestion:
Egestion is the act or process of discharging undigested or waste material from a cell or
organism. (NB: Compare with excretion)

List materials which are egested from the body:

cellulose and lignin from plant matter

the remains of intestinal epithelial cells
bile pigments
bacteria.

D.2 Applications 1 The reduction of stomach acid secretion

by proton pump inhibitor drugs.

State the role stomach mucus.

Mucus in the stomach is rich in bicarbonate, an alkaline compound, to help lubricate
and protect the stomach. Stomach acid comes from the parietal cells, a type of
stomach cell, and it is a hydrochloric acid, which is a solution of water and
hydrogen chloride. This allows the environment in the stomach to be highly acidic.
A high level of acidity is critical to inactivate bacteria in the food that people eat
and to activate pepsinogen.

State the cause of ulcer and acid reflux.

The decrease in the stomach's mucus lining that leads to an ulcer is
usually caused by one of the following: an infection with the bacterium
Helicobacter pylori (H. pylori) long-term use of nonsteroidal anti-inflammatory drugs
(NSAIDs), such as aspirin and ibuprofen.
Gastro-oesophageal reflux disease (GORD) is usually caused by the ring of
muscle at the bottom of the oesophagus (gullet) becoming weakened. Normally,
this ring of muscle opens to let food into your stomach and closes to stop stomach
acid leaking back up into your oesophagus. But for people with GORD, stomach acid
is able to pass back up into the oesophagus. This causes symptoms of GORD, which
can include heartburn and acid reflux.

Outline the role of the H+, K+ -ATPase protein pump in the production
of an acidic stomach.
Mechanism of Acid Secretion
The hydrogen ion concentration in parietal cell secretions is roughly 3 million fold
higher than in blood, and chloride is secreted against both a concentration and
electric gradient. Thus, the ability of the parietal cell to secrete acid is dependent
on active transport.
The key player in acid secretion is a H+/K+ ATPase or "proton pump" located in the
cannalicular membrane. This ATPase is magnesium-dependent, and not inhibitable
by ouabain. The current model for explaining acid secretion is as follows:

Hydrogen ions are generated within the parietal cell from dissociation of water. The
hydroxyl ions formed in this process rapidly combine with carbon dioxide to form
bicarbonate ion, a reaction cataylzed by carbonic anhydrase.

Bicarbonate is transported out of the basolateral membrane in exchange for

chloride. The outflow of bicarbonate into blood results in a slight elevation of blood
pH known as the "alkaline tide". This process serves to maintain intracellular pH in
the parietal cell.

Chloride and potassium ions are transported into the lumen of the cannaliculus by
conductance channels, and such is necessary for secretion of acid.

Hydrogen ion is pumped out of the cell, into the lumen, in exchange for potassium
through the action of the proton pump; potassium is thus effectively recycled.

Accumulation of osmotically-active hydrogen ion in the cannaliculus generates an

osmotic gradient across the membrane that results in outward diffusion of water the resulting gastric juice is 155 mM HCl and 15 mM KCl with a small amount of
NaCl.
(http://www.vivo.colostate.edu/hbooks/pathphys/digestion/stomach/parietal.html )

Outline the use, function and effect of proton pump inhibitors to treat
gastric disease.
Proton pump inhibitors (PPIs) block the gastric H,K-ATPase, inhibiting gastric acid
secretion. This effect enables healing of peptic ulcers, gastroesophageal reflux
disease (GERD), Barretts esophagus, and Zollinger-Ellison syndrome, as well as the
eradication of Helicobacter pylori as part of combination regimens.

D.2 Applications 2 Dehydration due to cholera toxin

Outline the cause and consequences of cholera infection.

Explain the effect of cholera toxin on intestinal cells.
There are an estimated 35 million cases of cholera, a disease caused by the
bacterium Vibrio cholera, each year. It is passed on through drinking water that

has been contaminated with faeces from someone infected with the bacteria.
Cholera causes vomiting and diarrhoea, leading to severe dehydration.

Ion channels and cholera

Ion channels are membrane proteins that, when open, allow ions (charged atoms)
to pass through them into or out of the cell. Several different things can open ion
channels: some ion channels open because of changes in voltage, and others open
because of a chemical (ligand) binding to them. In cholera, dehydration occurs
because of chloride ion channels.
A type of chloride ion channel called the cystic fibrosis transmembrane
conductance regulator (CFTR) normally pumps chloride ions out of cells. In small
intestine cells the CFTR channel is used to adjust water levels: a higher
concentration of chloride ions outside the cell will cause water to leave by osmosis.
Cholera disrupts this process.
How does cholera affect ion channels?
The cholera bacteria produce a toxin that is made of six protein subunits. The
cholera toxin binds to receptors on cells in the wall of the small intestine and
activates cyclic AMP (cyclic adenosine monophosphate, a messenger molecule),
increasing the number of cyclic AMP molecules in the cell.
As CFTR channels are activated by cyclic AMP, the increased concentration of cyclic
AMP causes the CFTR channels to open and stay open. They pump chloride ions (Cl -)
out of the cell into the lumen (the inside of the small intestine tube). Sodium ions
(Na+) are attracted to the negative chloride ions, so they also leave the cell.
With more ions in the lumen, the lumen has a lower water potential. This makes
water leave the cells lining the lumen by osmosis, down the concentration gradient.
The cells lose a lot of water, which causes severe dehydration, and the increased
water in the small intestine causes watery diarrhoea and vomiting.

D.2 Applictions 3

Helicobacter pylori infection as a cause of

stomach ulcers.

What is a stomach ulcer?

Stomach ulcers, also known as gastric ulcers, are open sores that develop on the
lining of the stomach. Ulcers can also occur in part of the intestine just beyond the
stomach these are known as duodenal ulcers. Both stomach and duodenal ulcers
are sometimes referred to as peptic ulcers.

Outline evidence that suggest Helicobacter pylori infection has a

role in stomach ulcer and stomach cancer.
Helicobacter pylori is an acid-tolerant bacterium that infects the lining of the
stomach. There is evidence that it causes several gastric diseases.

Stomach ulcers
These are areas of damage to the lining of the stomach. Old medical ideas
suggested that they are caused by excessive secretion of gastric juices, including
hydrochloric acid. There is now strog evidence to suggest that infection of the
stomach with H. Pylori is a more significant factor than gastric acid.
The evidence:
o Antacid treatments may relieve the symptoms of ulcers for a while, but not
permanently.
o Anti-microbial treatments that eliminate H. Pylori infection cure ulcers on a
long-term basis.
o H. Pylori infection is strongly associated with the presence of stomach
ulcers.
o Voluntary infection with the bacteria has shown that it can cause gastritis,
which often leads to ulceration.
o About half of the H. pylori strains isolated from patients with stomach
disease produced toxins that cause inflammation - and patients infected
with these strains tend to have the most severe ulceration.
o Proteases and other enzymes that are released by H. Pylori damage the
stomach lining.

Stomach cancer
Stomach cancer is the growth of tumours in the wall of the stomach. As with
stomach ulcers, a far higher percentage of patients with stomach cancer are
infected with H. Pylori than the general population. H. Pylori infection is associated
with reduced vitamin C concentration in gastric juice. This will increase the chance
of a tumour forming, but further research is needed to establish a causal link
between H. Pylori infection and stomach cancer.

D. 2 NATURE OF SCIENCE Serendipity and scientific

discoveriesthe role of gastric acid in digestion was established by
William Beaumont while observing the process of digestion in an
open wound caused by gunshot.
(NB: Serendipity is the occurrence and development of events by
chance which have happy or beneficial outcomes.)

Describe how William Beaumont was able to determine the role of the
stomach in chemical digestion of food. (Bizarre experiments in the
early 19th century, which involved dipping pieces of food through a
hole in an assistant's stomach, removing the food and then
examining it to see what had happened!) For instance: