2.2
The nervous system
The nervous system controls all aspects of body function. It consists of the central nerv-ous system, which includes the brain and spinal cord, and the peripheral nervnerv-ous system, which transmits messages from the brain to all the organs of the body and also receives messages about the body and the environment from the sensory system. The nervous system is made up of nerve cells and fibres, which carry electrical impulses from the brain, and also chemical transmitters, which amplify these electrical impulses at relay stations called synapses. The peripheral nervous system is subdivided into the voluntary system, which controls all muscular movements, and the autonomic system, which is not under voluntary control and ensures the function of all organs except the muscular system.
There are many chemical transmitters involved in both the central and peripheral nerv-ous systems. One of the most important is acetylcholine, which is the chemical transmit-ter between the end of the motor nerves and muscle fibres, and also in the end synapses of the parasympathetic nervous system.
2.2.1 The central nervous system
Key target: brain (including cerebrum, cerebellum hindbrain)
2.2.1.1 Normal function
The brain is a complex array of neurons grouped to control motor, sensory, posture and higher cognitive function. The brainstem controls much of the essential physiological activity, such as breathing. See section A4.1 of the appendix for more information on the normal functioning of the central nervous system.
Box 2.1 Definition of signs and symptoms
A symptom is an indication of disease, illness, injury, or that something is not right in the body. Symptoms are felt or noticed by a person, but may not easily be noticed by anyone else. For example chills, weakness, aching, shortness of breath, and a cough may be symptoms of pneumonia.
A sign is also an indication that something is not right in the body. But signs are defined as things that can be seen by a doctor, nurse, or other healthcare professional.
Fever, rapid breathing rate, and abnormal breathing sounds heard through a stethoscope may be signs of pneumonia.
2.2.1.2 Abnormal function
The cells of the central nervous system are very vulnerable to both direct and indirect actions of toxic substances, in particular lack of oxygen. Toxic effects on the central nervous system have profound effects on both higher cerebral functions, including consciousness, and the movements of the body and their control. Examples of manifestations of toxic Table 2.1 Some signs and symptoms, and possible chemical causes
Signs and symptoms Substance
Alopecia (loss of hair on the head) Arsenic, barium, bismuth, borates, carbon monoxide, gold compounds, lead, thallium
Amnesia (forgetfulness) Bromides, ethanol, hydrogen sulphide, methyl bromide Aplastic anaemia (lack of blood cells
due to failure of production by the bone marrow)
Arsine, benzene, carbon tetrachloride, lindane, nitrous oxide
Chest pain (heart-attack like) Cocaine, carbon disulphide
Convulsions (fits) Carbon monoxide, cyanide, lindane, opiates, arsenic, lead Diplopia (double vision) Bromide, carbomates, carbon dioxide, carbon disulphide,
carbon monoxide, ethanol, ethylene glycol, lead, mercury, methanol, methyl bromide, methyl chloride, organophosphate, trichloroethylene, triethyl tin
Eye irritation or redness Chlorine, ammonia, crowd control agents (e.g. CS gas) Fasciculations (visible involuntary
twitching of muscles)
Organophosphates, carbamates
Hallucinations Methyl chloride, some solvents, thiocyanates Hearing loss Bromates, carbon monoxide aminoglycosides such as
kanyamycin, toluene
Haematemesis (vomiting of blood) Acetone, acids, alkalis fluoride, formaldehyde, hypochlorites, phosphorus
Miosis (small or pinpoint pupils) Acetone, carbamates, organophosphates, opiates
Mydriasis (large or dilated pupils) Atropine, carbon dioxide, chloroform, cyanide, ethyl bromide, ethylene glycol, fluoride, methyl bromide, thallium, toluene Nystagmus (jerky movements of the
eyeball)
Arsenic, carbon disulphide, carbon monoxide, ethanol, ethyl bromide, ethylene glycol, gold compounds, manganese, methyl bromide, methyl chloride, organophosphates, toluene, xylene Photophobia (intolerance of or
hypersensitivity to light by the eyes)
Bromide, carbon dioxide, methanol, mercury
Skin irritation with defatting of skin and/or rashes
Acids, alkalis, alcohols, chlorinated compounds, ketones, nickel, phenol, trichloroethylene
Tinnitus (ringing in the ears) Arsenic, ethanol, trimethyltin, toluene
Upper respiratory tract irritation Oxides of nitrogen, oxides of sulphur, crowd control agents (e.g. CS gas)
Wheezing Chlorine, phosgene, oxides of nitrogen or sulphur,
organophosphates (inhalation), acrolein, asbestos, chromium, hydrogen sulphide, nickel, nitrogen dioxide, ozone, silica
damage or injury to the brain are coma, convulsions, impairment of memory, and distur-bances in gait.
2.2.2 The peripheral nervous system Key targets: sensory, autonomic, and motor nerves
2.2.2.1 Normal function
Sensory nerves . These are of varying sizes and transmit information about the body, such as pain and temperature, from special receptors.
Acetylcholine. Acetylcholine (ACh) is a major chemical neurotransmitter. It is released in small packets or vesicles from the nerve terminal and creates an amplified electrical response on the other side of the synapse. When this has happened the transmitter is very rapidly broken down by an enzyme called acetyl cholinesterase, which is present throughout the cholinergic nervous system.
The cholinergic nervous system. The control of the concentration of ACh is essential to the functioning of the cholinergic nervous system. This includes:
◆ Voluntary motor nerves: acetylcholine transmission at the neuromuscular junction.
◆ The autonomic nervous system: this comprises the parasympathetic and sympathetic systems. The parasympathetic system uses ACh as a transmitter whereas the sympa-thetic system uses noradrenaline. In general, the sympasympa-thetic system causes stimulation of body systems whereas the parasympathetic has the reverse effect. A good example is found in the nervous control of the heart.
Cholinergic effects are divided into muscarinic and nicotinic effects. These terms were derived from the actions of the compounds muscarine and nicotine during the early research into the cholinergic system. Muscarinic ACh receptors are found in the gut, heart (vagus), and pupil and accommodation muscles of the eye. The actions are blocked by atropine. Nicotinic ACh receptors control the voluntary nerve endings to muscle.
See section A4.2 of the appendix for more information on the normal functioning of the peripheral nervous system.
2.2.2.2 Abnormal function
Failure of the peripheral nervous system affects both the sensory and motor systems. The autonomic nervous system can also be affected. A direct toxic effect on nerves is called toxic neuropathy. This causes failure of nerve transmission due to the dysfunction of motor and large sensory fibres.
Failure of nerve conduction Toxic neuropathy affects nerve conduction by toxic effects on the myelin sheath of the nerve, which is essential for normal function. Many chemical substances cause damage to nerve conduction, a condition called toxic peripheral neu-ropathy. Examples include some organophosphate pesticides (no longer used in the UK) and industrial substances such as lead, thallium, triorthocresyl phosphate, carbon disul-phide, n-hexane, and acrylamide. Nerve conduction can also be affected by toxins. These are naturally occurring compounds that are produced by plant, animal, and aquatic organisms
and bacteria. Examples are tetrodotoxin and saxitoxin, which interrupt nerve conduction by blocking essential sodium ion channels in the nerve.
Finally, nerve conduction can also be interrupted by an inappropriate immune reaction from the body. An example is the Guillain Barré syndrome (acute idiopathic inflammatory polyneuropathy), which may be caused by a cell-mediated hypersensitivity (see section 2.8.2 in this chapter).
Failure of chemical transmission If the acetyl cholinesterase at the cholinergic synapses is reduced, this causes an increase in ACh at cholinergic synapses, causing poisoning by over-stimulation of the voluntary and autonomic cholinergic nervous systems. This is the case in organophosphate (OP) and carbamate pesticide poisoning. Increases in the ACh concentrations cause effects at all cholinergic synapses, both peripheral and in the central nervous system (Box 2.2 ). Further information on OP poisoning is found in Chapter 15 on pesticides.
Cholinergic synaptic transmission can also be affected by a reduction in the release of ACh from the nerve terminal. This is the case following intoxication by botulinum toxin as a result of food poisoning. In botulism there is muscle weakness, but the clinical picture is one of failure of cholinergic transmission rather than overstimulation, as in the case of pesticide poisoning. The muscles of the shoulder girdle, respiration and swallowing are particularly affected, creating the classic syndrome of botulism. The onset of paralysis is much slower than with anticholinesterase poisoning and the weakness can be overcome to an extent in the early stages by extra voluntary effort.
Alterations in transmission of impulses at cholinergic synapses have far-reaching effects on other body systems and target organs which are considered below.
2.3
The cardiovascular system (the heart and circulatory system)
Blood is transported through the body via a continuous system of blood vessels. This comprises arteries, capillaries, and veins. Arteries carry oxygenated blood away from the