This section is from the book "A Text-Book Of Pharmacology, Therapeutics And Materia Medica", by T. Lauder Brunton. Also available from Amazon: A text-book of pharmacology, therapeutics and materia medica.
The heavy metals have all a powerful poisonous action on muscles, nerves, nerve-centres, and glands. The slightness of the action which they exert on these structures when administered by the alimentary canal is due to their slow and sparing absorption by it. But their poisonous power at once becomes evident, as in the case of iron, when they are injected either sub-cutaneously or directly into the circulation in the form of double salts or organic compounds, which produce no local irritation at the point of injection, nor coagulation of the blood when they are introduced directly into the vessels. The alterations in the spinal cord in acute poisoning by some of them - e.g. lead and mercury, and also by arsenic - have the characters of acute central myelitis, the grey substance being chiefly affected. In more chronic poisoning the white substance is affected as well, so that the alterations resemble those of diffuse myelitis. The nervous symptoms produced by heavy metals are probably due to such alterations in the nerve-centres, and sometimes to peripheral alterations in the nerves also.
Metals are excreted chiefly by the bile (p. 405), by the kidneys, by the mucous membranes of the stomach and intestine; and probably to a slight extent by the skin. Elimination by these channels may commence very soon after the metal has entered the blood.
During the process of elimination the metals may irritate the eliminating organs (Fig. 5, p. 39), and may cause vomiting by their action on the stomach (p. 372), diarrhoea by their action on the intestine, and albuminuria by their action on the kidneys, although they have been injected into the veins, or subcutaneously, and only reach these organs through the blood.
1 This is best shown by separating the corpuscles and plasma in a centrifugal machine and analysing them separately, so as to ascertain the amount of metal in each.
When metals have entered the blood in considerable quantities, the kidneys become inflamed during the process of their excretion, and undergo changes which affect both the tubules and the glomeruli. The tubules are affected first, and the epithelial cells, both of the convoluted and straight tubules, take up the metal and become gradually disintegrated. They are partly thrown out as casts, and partly block up the tubules, causing secondary degeneration of the glomeruli. Both tubules and glomeruli become atrophied. These effects appear to be produced by all the heavy metals.
The possible effect of mercury on the kidneys should be borne in mind when prescribing a very prolonged mercurial course, and it would be interesting to inquire how far albuminuria in apparently healthy persons is caused by mercurials (cf. p.20). Group III. - Zinc, Copper, Cadmium, and Silver. General Actions. - They combine with albumen and form insoluble albuminates, and have thus an astringent action.
With the exception of salts of silver, which form a compound with the epidermis, they have no action on the epidermis, but they may pass through the pores, especially chloride of zinc. This salt produces inflammation, or even mortification, acting by its affinity both for water and for albumen. It is used as a caustic for destroying the surface of unhealthy sores and producing a more healthy action. The other preparations of the metals in this group act in the same way, but are less powerful, and are applied to ulcers and to chronic skin-diseases.
They are applied for their astringent action to the eye in gonorrhoeal ophthalmia, ulcerations or opacity of the cornea, and to the mucous membranes of the urethra and vagina in gonorrhoea and leucorrhoea.
Insoluble preparations such as oxide of zinc have little action on the skin, but are applied as powder or ointment to raw and excoriated surfaces, where protection from external influences with very slight stimulation is wished, as in intertrigo.
In the mouth they combine with the albumen of the tongue and cheeks, and produce a very disagreeable metallic taste. Notwithstanding this they are employed, especially sulphate of copper, for ulcers of the mouth or fauces.
Zinc chloride has been recommended for carious teeth.
In the stomach they unite with the albumen in its walls, producing irritation and consequent nausea, accompanied by muscular relaxation. They have been used as nauseants in spasmodic affections, as epilepsy, chorea, hysteria, etc.
In a somewhat larger dose they produce vomiting, which is speedy and complete, especially in the case of zinc and copper, which are consequently much used in cases of poisoning where we wish the stomach emptied with all possible speed. They are preferred in such cases to tartar emetic, as they do not produce so much depression, nor are they so liable to cause diarrhoea; and to ipecacuanha, because their action is more rapid and certain.
The compounds of zinc or copper with albumen or peptones will produce vomiting, either when given by the mouth or when injected into the veins, but they are classed as local emetics (p. 373).
Their emetic action when injected into the veins may be due to a direct action on the vomiting centre in the medulla (p. 371); but it may also be that they are carried to the stomach by the blood and act reflexly from it (vide Fig. 5, p. 39, and cf. p. 373).
The albuminates of copper and zinc, and probably those of the other metals, undergo changes both in the stomach and intestine before absorption which we do not perfectly understand. Albumen is not simply dissolved and absorbed in the intestinal canal, but is converted into peptone. Albuminate of copper has been introduced into a gastric fistula in a dog, and the blue colour was seen to disappear at the edges, and finally all copper was removed from it before the albumen was itself completely digested. Whether or not the copper was removed in combination as a peptone or not we cannot as yet say. Copper salts unite with peptone, forming an easily soluble compound.
In the intestine small doses lessen the frequency of the stools, and have been thus used in chronic diarrhoea and dysentery, but larger doses have an irritant effect and cause diarrhoea. The insoluble salts, as oxide and carbonate of zinc, have a much weaker action than the soluble ones, and thus a large quantity of them has the same action as a small one of the soluble salts.
Chronic poisoning by copper is said to have occurred in consequence of the use of copper salts to give a bright green colour to tinned peas or other vegetables, as well as from the employment of imperfectly cleansed copper pans. Some doubt has been thrown on the possibility of producing chronic poisoning by the internal administration of copper in small doses, as in some experiments it was given to animals for a length of time without injury. More recent experiments show, however, that at least in ruminants chronic poisoning may be produced. The symptoms are loss of appetite, imperfect rumination, periodical constipation, imperfect nutrition, muscular weakness, languor, jaundice, albuminuria, and towards the end haemoglobinuria or haematuria. On post-mortem examination granular degeneration of the muscles and heart, enlarged spleen, fatty degeneration of the liver, dark brown colour of the blood, and granular deposits of methaemoglobin in the renal tubules, along with haemorrhagic parenchymatous nephritis, are found.
Chronic poisoning by copper may occur among coppersmiths, or in families where copper pans have been used. The symptoms are a metallic taste, a feverish state, with symptoms of subacute gastro-enteritis, not unfrequently jaundice, trembling of limbs, and cramps. A purple line is said to form on the gums.