Lecture 1: Introduction: Overall function of the digestive system

1. Describe the general physiological functions of gastrointestinal system

2. Discuss electrical activity of smooth muscle
3. Discuss mechanism of contraction in smooth muscle
4. Correlate between electrical and mechanical functions in smooth muscle
5. Outline the regulation of different functions in GI system
6. Relate the enteric nerve plexuses to their functions
7. Correlate between intrinsic and extrinsic nerve supply of GI system
8. Appraise role of GI hormones
9. Correlate between different motility and their functions

The overall function of the digestive system is to transfer the nutrients to the internal
environment, to be distributed to all cells via the circulation.

Components of the digestive system:

I- The gastrointestinal tract (GIT) is a tube of variable diameter, ~15 feet long in
living adults. It extends through the mouth, oesophagus, stomach, small intestine, and
large intestine ends by the anus.
II- The associated organs situated outside the tract; are exocrine glands that secrete
important digestive juices.
● The 3 pairs of salivary glands produce saliva into the mouth
● The exocrine pancreas secretes pancreatic juice in the small intestine
● The liver produces bile into the small intestine.
III- Accessory organs include tongue, teeth, and muscles of mastication

Physiological processes of the digestive system:

1. Exocrine gland secretions of enzymes, ions, water, mucins, and other substances. The
glandular cells are situated within the wall of GIT, or as separate associated glands.

2. Motility helps to mix the contents of the lumen and move them through the tract.
3. Digestion is break-down of large molecules to smaller ones easily to be absorbed e.g.,
glucose and amino acids.
4. Absorption is the central function. The absorbable products of digestion, ions and water
are transported across the epithelial cell, mainly in the small intestine to the blood or
lymph.
5. GIT is the largest endocrine organ in the body, but the hormone-secreting cells are
scattered in the mucosa. These endocrine cells are amine precursor uptake and
decarboxylation cells (APUD).
6. Immune function: Humoral antibodies and cellular immune system in GIT protect the
body against micro-organisms enter the lumen with ingested materials.

7. Excretion Some substances are excreted, by the liver in the bile as waste metabolites and
drugs. The faeces are composed of gut bacteria, and 30–40% undigested unabsorbable
material such as cellulose, in addition to excreted metabolites such as the bile pigments.

1
Quantities of material processed by the GIT
An adult consumes about 800 g of food and upto 2 litres of water per day. In addition, secretion
into the tract may amount to 7–8L of fluid (9–10L of fluid / day).
Only 5–10% pass to the colon and only 150 g/day is eliminated from the body as faeces.

Smooth muscle in the gastrointestinal tract

The muscular coat of GIT is composed of smooth muscle. However, skeletal muscle is present in
the pharynx, the upper third of the oesophagus, and the external anal sphincter.
The smooth muscles are arranged mainly in 2 layers, an outer longitudinal, and an inner circular.
They are of two types, depends on the electrical properties of the cell, but the basic contractile
mechanisms are similar in all cells.
 Phasic muscle contracts and relaxes in a matter of seconds. This is present in the main
body of the oesophagus, the gastric antrum and the small intestine.
 Tonic muscle contracts in a slow and sustained manner for minutes or hours. This is
present in the lower oesophageal, ileocaecal and the internal anal sphincters.

General structure of smooth muscles:

- The smooth muscle is composed of spindle- shaped cells. Unlike skeletal muscle, cells are not
arranged in orderly sarcomeres, and no striations. It has a rudimentary sarcoplasmic
reticulum and calcium stores.
- Smooth muscle lacks the specific neuromuscular junctions of skeletal muscle. Instead, the
autonomic fibers, have numerous bulbous swellings, called varicosities. The varicosities
release neurotransmitter into a wide synaptic cleft called diffuse junctions.
- Thick and thin myofilaments are present; actin and tropomyosin constitute the thin filaments
and myosin is the thick filaments. Troponin is present in negligible amounts.
- The thin filaments are anchored either to the plasma membrane or to the dense bodies that
correspond to the Z lines in skeletal muscle. Dense bodies are attached to a network of
intermediate thickness filaments that form an internal skeleton.
- The muscle cells are organized as sheets and behave as units.
- Opposing membranes of the cells are fused to form gap junctions with low electrical
resistance, that allow the spread of excitation wave from cell to another. Contractions of the
bundles of cells are therefore synchronous.

Basic electrical rhythm (slow waves)

 Except in the oesophagus and the proximal portion of the stomach, the smooth muscle of the
GIT specific smooth muscle -like cells that has spontaneous rhythmic fluctuations in
membrane potential between about –65 and –45 mV in the absence of external stimulation.
These cells are numerous in the longitudinal muscle layer. Their resting membrane potential
(RMP) is continuously oscillating and is known as the basal electrical rhythm(BER).
 BER is initiated by the interstitial cells of Cajal; pacemaker cells, that send long branched
processes between muscle cells.
 If the amplitude of the depolarization phase of the oscillation reaches the threshold, an action
potential is triggered, transmitted throughout the muscle sheet and conducted via gap
junctions from cell to cell.

2
 The depolarizing portion of each spike is due to Ca2+ influx, and the repolarizing portion is
due to K+ efflux.
 The BER itself rarely causes muscle contraction, but spike potentials causes muscle
contraction and increases muscle tension.
 The membrane potential of the pacemakers is controlled by neurotransmitters and
hormones. These act on receptors to cause either depolarization or hyperpolarization of
the cells.
 Factors that make smooth muscle membrane more excitable (i.e. increase the frequency
and magnitude of the BER and produce more spike potentials) are (1) stretching of the
muscle, (2) acetylcholine released from the parasympathetic nerves, and (3) stimulation
by several gastrointestinal hormones.
 The rate of the BER is about 4/min in the stomach. It is about 12/min in the duodenum
and falls to about 8/min in the distal ileum. In the colon, the BER rate rises from about
2/min at the cecum to about 6/min at the sigmoid.

Mechanism of smooth muscle contraction:

Contractions of smooth muscle occur by a sliding filament mechanism and cross-bridge
formation.
In resting muscle, the ICF Ca2 concentration is lower than the extracellular and no interaction
between actin and myosin.
 The action potentials occur spontaneously in pacemaker cells in the absence of external
stimulation. Action potential is transmitted via gap junctions from cell to cell.
 Action potential of phasic muscle cells triggers Ca2 influx via voltage-determined Ca2
channels (VDCCs). This initiates the contractile response of the non-pacemaker cells.
 Inside the cell, the Ca2 binds to calmodulin (Ca2 binding protein). This complex activates a
kinase enzyme in the myosin filaments that phosphorylate myosin, utilizing ATP. The
phosphorylated myosin interact with actin, causing the movement of the cross bridges and
the muscle contracts.
 The process of attachment and detachment of actin to myosin in smooth muscle is much
slower than in skeletal muscle. The energy needed to sustain smooth muscle contraction is
very small.
 Then myosin is inactivated by phosphatase enzyme causes split the phosphate from its
heads.
 For smooth muscle relaxation to occur, calcium ions must be removed by the calcium pump.
Calcium pump in smooth muscle is much slower than in skeletal muscle.

With increased frequency of action potentials there is increased Ca2 influx leads increased force
of contraction. Conversely, a reduction in Ca2 influx leads to a decrease in the force of
contraction, i.e. relative relaxation.

Neurotransmitters, hormones and others can promote Ca2 influx & trigger contraction of smooth
muscle.
Smooth muscle contracts in response to stretch; the myogenic reflex, an intrinsic property of
smooth muscle. Stretching the membrane opens Ca2 channels and Ca2 flows into the cell.

3
However, whereas moderate stretch results in depolarization of the membrane and muscle
contraction, excessive stretch inhibits the force of contraction.

Control of GIT functions: is by neural, hormonal and paracrine mechanisms.

I- Neural control The GIT is innervated by

A. Enteric nervous system: regarded as a third division of ANS. However, it can perform
many functions independently of the CNS.
There are both excitatory and inhibitory nerves and interneurones and different excitatory
and inhibitory neurotransmitters. Furthermore, it exhibit spontaneous rhythmic activity.
The enteric nervous system consists of
a. The myenteric plexus (Auerbach’s plexus), situated between the longitudinal and
circular smooth muscle, and is involved mainly in the control of GI motility
b. The submucous plexus (Meissner’s plexus), lies in the mucosa and is important in
the control of secretion and blood flow. It is also important in receiving sensory
information from the gut epithelium and from stretch receptors in the wall of the tract.
Within each plexus the neurons are arranged in ganglia, and their axons connect the plexi
together. They also may innervate smooth muscle, secretory glands and blood vessels directly. In
addition may synapse with postganglionic sympahetic and parasympathetic nerves, or sensory
nerves.
The enteric nervous system is composed of
Intrinsic motor neurones
 Excitatory motor nerves are predominantly. Some are cholinergic and the receptors
involved are muscarinic. However, others release substance P. They cause contraction of
both circular and longitudinal muscle, relaxation of sphincters, or glandular secretion.
 Inhibitory motor fibres cause smooth muscle relaxation. The inhibitory transmitters
involved may be ATP or vasoactive intestinal peptide (VIP).

Intrinsic interneurones
Interneurones can also be excitatory or inhibitory. The transmitter released by excitatory
neurones is probably acetylcholine that acts on nicotinic receptors. The inhibitory transmitters
are unknown.

Sensory neurones Many afferent sensory neurones are present in the GIT.
 Some of these have their cell bodies in the enteric nervous system. They are stimulated
by distension or irritation of the gut that activates mechanoreceptors and by substances in
the food, which activate chemoreceptors. They form part of reflex pathways, which may
or may not be influenced by extrinsic nerves. Some afferents terminate in the sympathetic
ganglia.
 Other sensory fibres from the GIT have their cell bodies in the dorsal root ganglia of the
spinal cord or in the cranial nerve ganglia. They transmit information to the medulla,
which in turn transmits efferent signals back to the GIT controlling its functions.

4
 B. Autonomic nerves can alter the activity of the entire GIT, or a part of it, via its
influences on the enteric nervous system. In addition, they may synapse directly on
smooth muscle and secretory cells to influence their activity.

1- Parasympathetic nerves
The cranial preganglionic vagal fibres innervate from oesophagus down to proximal
half of transverse colon. The preganglionic nerves of 2, 3 and 4 sacral segments travel
in the pelvic nerves to the distal part of the large intestine.
The preganglionic fibres synapses with the interneurons of enteric plexi. These are
mainly excitatory interneurones, release acetylcholine, act on nicotinic receptors.
Stimulation of the parasympathetic nerves can have a diffuse effect to activate the
entire enteric nervous system to stimulate secretion and motility.

2- Sympathetic nerves
The preganglionic sympathetic from T8–L2 spinal segments synapse in the coeliac
ganglion and various mesenteric ganglia. The postganglionic fibres terminate on
neurones in the enteric nerve plexi, or directly on muscle or secretory cells.
Sympathetics inhibits activity in the GIT indirectly by inhibit the release of
acetylcholine and causes relaxation of the muscle. They can also cause constriction of
sphincters, or inhibit glandular secretion, and importantly, cause vasoconstriction of
arterioles. The transmitter released by postganglionic nerve fibres is noradrenaline.

II- Paracrine and Endocrine control

APUD cells sense chemical substances in the food and respond to mechanical stimulation. They
release hormones into the interstitial spaces where they can regulate cells that are in close
proxim- ity to the hormone release sites. This local influences are known as paracrine control.
And from there they are transported by diffusion or vesicular transport (cytopempsis) into the
blood capillaries. Hormones circulate in the blood to act at sites that may be distant from the
location where they are secreted.

Blood flow to GIT and its regulation:

Splanchnic circulation accounts to 25% of COP. It functions to provide fuel to enable the
functions of GIT. It also functions as a storage site for of blood.
The blood vessels of the splanchnic circulation are arranged both in series and parallel, and most
of blood flows through the liver, either directly, or after passing through other abdominal organs.
It leaves the liver via the hepatic veins to the inferior vena cava. The branches of the major
arteries give rise to smaller branches that penetrate the organs. Smaller branches divide to give
rise to an extensive network of small arteries in the submucosa and mucosal arterioles that carry
the blood to the capillaries. This arrangement leads to considerable overlap in the distribution of
blood, and helps to prevent loss of blood flow to a specific region if a major arterial branch is
occluded.
The blood flow to the GI organs is relatively low and it increases several-fold with meals.
It is controlled by many factors including

5
  Haemodynamic factors such as cardiac output, systemic arterial pressure, blood
viscosity and blood volume, as all tissues in the body.
 Vasoconstrictive factors include:
- Sympathetic activity via noradrenaline on α- receptors. However this effect is short-lived
and affected by local factors as reduction in oxygen tension (hypoxia), that induces
vasodilatation. In addition sympathetic relaxes gut muscle which results in reduced
mechanical resistance to blood flow.
- Circulating adrenaline, angiotensin II and vasopressin.
 Vasodilator factors include:
- The parasympathetic increases the blood flow by indirect mechanisms. It increases
activity and metabolism of the secreting tissues, increases metabolites such as K, amines
and polypeptides, and CO2, and reduced O2 tension, all may cause localized
vasodilatation. The transmitter released from these parasympathetic nerves may be VIP.

- Secretory tissues release of kallikreins, which activate the bradykinin, to form the active
vasodilator.
- Hormones have a localized effect; with gastrin increasing the blood flow to the stomach
and CCK increasing blood to pancreas and intestines.

Phases of control of GI functions during a meal

The presence of food in the GIT stimulates smooth muscle in the main body of the tract and the
gall bladder, relaxes the sphincters, and stimulates secretion and blood flow.

The control can be considered in three phases, depending on the location of the food:

1. The cephalic phase the presence of food in the mouth.

2. The gastric phase is due to the presence of food in the stomach.
3. The intestinal phase is when the food is present in the small intestines.