Guyton Medical Physiology:
Digestion
Chapter 61: autonomic nervous system and adrenal medulla
The autonomic nervous system is the portion of the nervous system that controls most visceral
functions of the body such as arterial pressure, GI-motility, GI-secretion, urinary bladder emptying,
sweating and body temperature. It is very rapid and intense. It is activated by the spinal cord, brain
stem and hypothalamus. It can be divided into a sympathetic (SNS) and a parasympathetic (PNS)
nervous system.
The SNS consists of two paravertrebral sympathetic chains of ganglia that interconnected via spinal
nerves, prevertebral ganglia (celiac, superior mesenteric, aortico-renal, inferior mesenteric and
hypogastric) and nerves extending from the ganglia to the internal organs. In contrast to the skeletal
motor pathways, SNS pathways consist of two neurons from the cord to the target tissue; a pre- and
a postganglionic neuron. The pathway they take can have three ways; synapse with postganglionic
SNS neurons in the ganglion that they enter, they can pass upwards or downwards in the chain of
ganglia, or they can pass distances through the chain and eventually synapse on peripheral SNS
ganglia. The terminants of the different segments of the spinal cord do not always correspond to the
same part of the body as the somatic spinal nerve fibres that terminate from that part of the spinal
cord. The distribution is mostly determined by the origin of the locus in the embryo. Some
preganglionic nerve fibres pass through all the chains, without synapsing, synapse directly onto
modified neuronal cells that secrete (nor)epinephrine in the adrenal medulla.
The PNS leaves the CNS through cranial nerves III, VII, IX and X and through S2,3 and 4 on the lower
most part of the spinal cord. About 75% of a PNS nerve fibres are in the vagus nerves (X). The PNS
also consists of both pre- and postganglionic nerves. However, in contrast to the SNS nerves, most of
them pass all the way to the controlled organ without synapsing before. Additionally, a second
difference between the SNS and PNS is the location of the postganglionic neurons. In the SNS they
located mostly in the ganglia of the chain instead of in the controlled organ itself, like the PNS.
The two most important synaptic transmitters in the nervous system are acetylcholine (cholinergic)
and norepinephrine (adrenergic). In the SNS: preganglionic neurons are cholinergic and
postganglionic neurons are adrenergic (except for sweat glands and a few blood vessels). In the PNS:
preganglionic neurons are cholinergic, and the postganglionic neurons as well. The secretion site of
the neurotransmitters in the nerve endings (postganglionic) are quite similar to skeletal
neuromuscular junctions. On the way to the controlled organ they pass by and touch effector cells.
Those places where they touch or pass by often have enlargements called varicosities. These contain
the vesicles with the neurotransmitters and also synthesize new ones. Acetylcholine is synthesized
from Acetyl-CoA + choline + choline acetyltransferase and later it is broken down by
acetylcholinesterase into an acetate ion and choline. The choline is then recycled and reused for the
new synthesis. The synthesis of norepinephrine is a bit more complicated than acetylcholine. The
basic steps are from tyrosine to dopa, from dopa to dopamine, then the dopamine is transported
into the vesicles, the dopamine is hydroxylated into norepinephrine. In the adrenal medulla 80% of
norepinephrine is methylated into epinephrine. After secretion there are several ways of getting rid
of the norepinephrine again. It can be taken up again into adrenergic nerve endings, diffused away
into surrounding body fluids or destructed by tissue enzymes (mainly liver after secreted in blood).
, Before the neurotransmitters stimulate the effector organ, they need to bind to specific receptors.
This causes either a change in cell membrane permeability or (in)activation of an enzyme attached to
the receptor protein (second messenger).
The cholinergic and adrenergic receptors also differ from each other. For cholinergic they consist of
muscarinic and nicotinic receptors. Muscarinic uses a G-protein (second messenger) and are found on
the effector cells of postganglionic neurons from either the SNS or PNS. Nicotinic receptors are
ligand-gated ion channels and are found in ganglia in the synapses between the pre- and
postganglionic neurons of both the SNS and PNS. For adrenergic receptors there are alpha and beta
receptors. They both work via G-proteins. Norepinephrine excites mainly alpha receptors but also a
few beta receptors, while epinephrine excites both equally. Therefore, it depends on which receptors
are present to determine if either norepinephrine or epinephrine will be more effective. Alpha and
beta receptors are not necessarily associated with excitation or inhibition but with the affinity of the
hormone in the effector organ. A synthetic hormone called isopropyl norepinephrine has an
extremely strong activation on beta receptors but no action on alpha receptors.
SNS and PNS sometimes act reciprocally to each other. They both have very different actions on the
body parts (see Table 61-2 in Guyton p779).
The adrenal medullae is stimulated by the SNS and therefore secretes (nor)epinephrine into the
bloodstream. The effects of those last 5-10 times longer than with direct stimulation. Norepinephrine
and epinephrine also differ from each other. Epinephrine has a greater cardiac stimulation,
norepinephrine has a greater effect on constriction of blood vessels and epinephrine has a greater
metabolic effect. The dual mechanism of sympathetic stimulation (adrenal medullae and directly by
nerves) provides a safety factor, with one mechanism substituting for the other if missing.
Previously was mentioned that there are a lot of similarities between the autonomic system and the
skeletal system. However, a big difference is that the autonomic system only requires a low
frequency of stimulation for full activation of effectors. The autonomic nervous system, both the SNS
and PNS, are continually active and the basal rate are known as tone. This tone allows a single
nervous system to both increase and decrease the activity of a stimulated organ.
If you were to cut sympathetic nerves in the forearm and later inject portions of norepinephrine,
there is a cascade of things that would happen called; denervation supersensitivity. First the blood
flow rises due to loss of vascular tone but gets restored because of the intrinsic tone of vascular
musculature itself. Then when a second dose of norepinephrine is administered later, the blood flow
decreases much more due to increased sensitivity to the norepinephrine because of up-regulation of
the receptors.
The SNS is sometimes discharging simultaneously in all portions, called mass discharge. This mostly
happens when the hypothalamus is activated by fright of pain resulting in a widespread reaction
called the alarm or stress response. At other times only isolated portions or the SNS are activated
such as sweat and blood flow in the skin in heat response, local reflexes and the paravertrebral
ganglia in the GI-tract to control motor or secretory activity. The alarm/stress response has a lot of
influence on several parts of the body: increased arterial pressure, increased blood flow to active
muscles, increased cellular metabolism rates, increased blood glucose concentration, increased
glycolysis in liver and muscles, increased muscle strength, increased mental activity and increased
rate of blood coagulation.
There are also some drugs that stimulate or block the autonomous nervous system. Some important
ones that activate the SNS are norepinephrine, methoxamine, phenylephrine, isoproterenol and
albuterol. The last three are adrenergic receptor drugs. Blockers are reserpine, guanethidine,
prazosin, terazosin, yohimbine and more. Important drugs that activate the PNS are pilocarpine and
