DIAGNOSIS OF POISONING

DIAGNOSIS OF POISONING

            Under the field conditions, every unknown disease is usually suspected to be some sort of poisoning. Effective treatment can only be adopted if proper diagnosis is made. Therefore, a successful veterinarian or clinical toxicologist should be able to distinguish between poisoning and other disease states.

            Diagnosis in case of poisoning may be of three types: tentative, presumptive and confirmative.

            A tentative diagnosis is first made from the case history, by clinical examination of the affected animal and carefully observing the gross necropsy changes. This helps in elimination of other diseases. Investigations should be made to find out the access of the animals to any toxicant or its use in their vicinity, which also help in arriving at the tentative diagnosis.

            The presumptive diagnosis can be arrived basing on the correct history, characteristic clinical signs and pathological observations in association with the knowledge of access to the suspected toxicant has occurred. Successful use of antidotal therapy supports the presumptive diagnosis.

            The confirmative diagnosis can be made by both qualitative and quantitative estimation of the toxicant in the feed, water, ruminal contents or animal tissues.

            Diagnosis of poisoning is based on the following points:

1.      History

2.       Circumstantial evidence

3.       Symptomatic evidence (Clinical evidence)

4.       Pathological evidence

5.       Analytical evidence

6.       Experimental evidence

7.       Therapeutic evidence (Response to treatment)

            A. History: It is of limited value. It gives important clues of the suspected poisoning. Detailed history of poisoning should be extracted from the animal owner / attendant. It is not possible to get all the details every time / at times it may be inaccurate and misleading. The following points may contribute to the diagnosis of poisoning:

            Health history: illness in the recent past; vaccination history; medications – their dose, route and duration; sprays, dips, anthelmintics; their dose, route and if the drug(s) given to some other animal also; If drug is given to the same animal only, try to obtain the sample of the drug.

            Current clinical history: Size of the herd/flock; Animals purchased or home raised; For herds/flocks, what is the morbidity and mortality; When first observed sick; Persistance of problem in the herd/ flock; If animal(s) found dead, how long since seen alive and healthy  

            Diet/Food: Type of diet; Recent changes in diet; Change in method of feeding; Source of diet and drinking water; Presence of spoiled or mouldy feed/food;  

            Onset of action: If onset of action is sudden or symptoms develop gradually; If onset of action occurs after meal, drink or medicine; If vomiting or diarrhoea occurs before the onset of toxic symptoms

            Clinical signs: Types of clinical signs seen, e.g. ataxia, salivation, excitation, seizures, vomiting, diarrhoea, etc.

            B. Circumstantial Evidence This is very important, and may provide a rapid and simple step towards making a diagnosis. It attempts to answer the question 'What poison, if any, was available to the animal?' and is provided by inter­rogation of the owner and, if possible, by a personal search of the buildings and their surroundings. It is often convenient to deal with poisons under four headings: housing, food, medicine and environment; and to consider the hazards that may arise from each in turn.

            Consider first the animal's housing: Has any part of it been painted recently? Has tar or creosote been used? Is the paint old or flaking? Is there any loose roofing felt, or torn linoleum? Is the ventilation adequate? Has any new furni­ture or equipment been introduced? If overcrowding of animals; If new furniture or equipment is added in the house; If animal shed/house is near some industry, drainage, etc.; Shed/pillars, if sprayed recently with insecticide; Changes in exposure (e.g. recently moved, renovation of old buildings, manure removal); In small animals, if housebound or roam freely

            Turn next to the question of food: Has there been any change in the diet? Has anything abnormal been noticed in the food? Has there been a new con­signment? Samples of anything relevant should be taken in case they are needed for analysis, but all too often the offending sack has been finished, and a new and possibly innocuous one, opened. Water supply must also be considered. It may contain lead, or salt, or nitrite. Storage conditions of food; Condition of food, i.e. mouldy, wet, etc.; Water, if given from pond. If so, sanitary/condition of pond

            The question of medicines includes food additives. Have these been given in the right quantity? Additives intended for cattle should not be given to horses, nor those meant for pigs to sheep. Have any proprietary brands of medicine been given? If so, try to obtain a sample. (The authors once met worm capsules made up with corrosive sublimate instead of calomel.) Have animals (particularly puppies) had access to any tablets meant for human consumption?

            Finally there is the problem of environmental hazards, which includes everything from atmospheric pollution to snakes in the grass. The first question must be that of pesticides. Has any spray been used on the farm or in the garden? If so, it is important to examine the container to find what it really contained. If the product is not recognized, a phone call to the manufacturers may be helpful. Has any bait been put down for rats? In this case the local authority may help to identify the compound used. Then pollution: Are there any factories, or tips, or dumps, up wind or up stream? Are there any poisonous plants? The help of a botanist may be useful here. Finally, a search should be made for anything left carelessly lying about-old car batteries, sump oil, antifreeze or tarpaulins blown off lorries.

            There may be other clues to the origin of poisoning. The odour of the breath may be characteristic, e.g. phenols and creosote (phenolic), cyanide (bitter almonds), phosphorus (garlic), hemlock (mice), paraffin. The urine is coloured dark green in poisoning with phenols and creosote, red after administration of phenothiazine, brown or black after ingestion of acorns, deep yellow after phenacetin and picric acid.

            This list is by no means complete but may at least serve to indicate the wide variety of poisons which can give rise to the same or similar symptoms.

            Important though it is, circumstantial evidence cannot alone provide the basis for a diagnosis of poisoning. It is only too easy to jump to conclusions.

             C. Symptomatic Evidence (Clinical evidence) This is based on the veterinary surgeon's own ob­servations, or, if the animal is dead before he sees it, on the case history given by its owner, which will almost certainly be inaccurate. At its best, however, clinical evidence is only of limited value, because of

a. Different toxicants produce same type of symptoms, or toxicants of same group produce different symptoms. For example, BHC and aldrin produce CNS stimulation and depression, respectively, though both belong to organochlorine group of insecticides.

b. One toxicant is neutralised or potentiated by another toxicant, e.g. barbiturates with alcohol (potentiation),

c. Same toxicant produces different symptoms in different species of animals. For example, morphine produces CNS depression in most mammals but CNS stimulation in cat.

d. Some signs of poisoning (e.g. vomiting, seizures) can also be produced by infectious diseases or metabolic and endocrine dis­orders.

e. The clinician see only one phase of the progression of the disease.  

            There are only nine systems of organs in the body that are capable of being affected, so the permutations and combina­tions of clinical signs are extremely limited. In addition there is extraordinary variability shown by different individuals in the symptoms caused by the same poison. Not every symptom appears on each occasion. Thus any list of 'symptoms' for any given poison must be treated with very considerable reserve. Quite atypical signs may occur.

            In such cases owner should be asked if he has seen other signs. Inspite of the above limitations, speed of onset and duration of signs may identify some of the toxicants and rule out others. Similarly, morbidity and mortality rates may give clue to the type of toxicant.           

            The more common clinical signs that may be encountered with the more important poisons that may cause them: 

Abdominal pain: aflatoxin, ammonium salts, arsenic, chlorate, chromate, con­centrated acids and alkalis, copper, lead, nitrite, phenothiazine, phosphorus, selenium, zinc, zinc phosphide, box, buttercups, oak, rhododendron.

Anaemia: cadmium, copper, lead, thallium, kale.

Anorexia: aflatoxin, arsenic, benzoic acid (cat), carbon tetrachloride, chromate, copper, gossypol, kerosine, lead, mercury, phenol, phenothiazine, pheno-acidic herbicides, oxalate, salicylate (cat), sodium chloride (pig), thallium, TOCP, zinc phosphide, bracken (bovine), ragwort, oak.

Ataxia: aflatoxin, ammonium salts, arsenic, atropine, barbiturates, carbon monoxide, carbon tetrachloride, chlorate, chlorpromazine, ethylene glycol, gossypol, mercury, metaldehyde, molybdenum, nicotine, nitrite, pheno­thiazine, phenoxyacidic herbicides, organochlorine insecticides, selenium, sodium chloride (pig), bracken (horse), buttercups, castor seed, hemlock, laburnum, ragwort, rhododendron, yew, snake bite.

Blindness: aflatoxin, atropine, lead, mercury, selenium, sodium chloride (pig), buttercup, ergot, rape.

Coma: alphachloralose, barbiturates, carbon monoxide, chlorpromazine, cyanide, ethylene glycol, hydrogen sulphide, metaldehyde, nicotine, phenol, organo­chlorine and organophosphorus insecticides, zinc phosphide, laburnum, potato.

Convulsions: alphachloralose, atropine, benzoic acid (cat), caffeine, copper, cyanide, ethylene glycol, fluoroacetate, gossypol, hydrogen sulphide, lead, metaldehyde, nitrite, organochlorine and organophosphorus insecticides, phenol, phosphorus, sodium chloride (pig), strychnine, box, bracken (horse), ergot, laburnum, water dropwort, water hemlock.

Depression and weakness: aflatoxin, arsenic, barbiturates, carbon monoxide, carbon tetrachloride, chlorpromazine, copper, ethylene glycol, gossypol, kerosine, mercury, nitrite, oxalate, phenol, phenoxyacidic herbicides, sali­cylate (cat), thallium, bracken (bovine), buttercup, castor seed, hemlock, oak, ragwort, rhododendron, snake bite.

Diarrhoea: arsenic, cadmium, carbon tetrachloride, chlorate, chromate, gossypol, lead, molybdenum, nitrite, thallium, TOCP, warfarin, zinc, box, bracken (bovine), buttercups, castor seed, ergot, oak, potato, water dropwort, water hemlock.

Dilation of pupils: atropine, barbiturates, strychnine, hemlock, water dropwort, water hemlock, snake bite.

Dyspnoea: ammonium salts, antu, atropine, carbon monoxide; chromate, cyanide, hydrogen sulphide, kerosine, organophosphorus insecticides, oxalates, phenothiazine, selenium, sulphur, warfarin, bracken (bovine), hemlock, yew.

Haematuria: chlorate, copper, mercury, warfarin, bracken, buttercups, kale, oak, rape.

Icterus: aflatoxin, arsenic, copper, phenothiazine, phosphorus, ragwort.

Lameness: fluorine, selenium, TOCP, warfarin, ergot, tall fescue.

Paralysis: carbon monoxide, copper, cyanide, nicotine, organophosphorus in­secticides, phosphorus, selenium, TOCP.

Photosensitization: phenothiazine, Pithomyces chartarum, and numerous poison­ous plants.

Salivation: arsenic, copper, cyanide, metaldehyde, organochlorine and organo­phosphorus insecticides, oxalate, phosphorus, sodium chloride (pig), strychnine, thallium, buttercups, potato, rhododendron, water dropwort, water hemlock, toad venom.

Thirst: arsenic, chlorate, chromate, sodium chloride (pig).

Twitching of muscles: atropine, kerosine, metaldehyde, organochlorine and organophosphorus insecticides, phenol, sodium chloride (pig), bracken (horse), yew, snake bite.

Vomiting: antu, arsenic, cadmium, copper, lead, phenoxyacidic herbicides, phosphorus, salicylates, sulphur, thallium, warfarin, zinc, castor seed, laburnum, potatoes, rhododendron, water dropwort, water hemlock.

            D. Pathological Evidence The lesions of poisoning are rarely characteristic; nevertheless, the findings at autopsy can provide definite clues to the nature of the poison. The absence of lesions may be as important as their presence as it serves to exclude various toxic agents. The discovery of severe traumatic lesions will eliminate the possibility of poisoning altogether.

            The skin and visible mucous membranes may have a characteristic dis­colouration.

Jaundice is a frequent sign of hepatic damage in small animals (e.g. phosphorus poisoning) but is less often seen in ruminants; causes in the latter species include lupin, ragwort and chronic copper poisoning.

A cherry red or pink colour is seen in carbon monoxide and cyanide poisoning.

Methaemo­globinaemia due to nitrates, nitrites or chlorates may impart a brown colouration.

            Upon opening of the abdominal cavity a typical odour may be noted (as in cyanide poisoning), and this may be more obvious when the stomach itself is opened (e.g. phosphorus, phenols).

            The nature of the stomach contents may be of interest. Careful search should be made for recognizable or suspicious traces of poison, or of a poisonous plant; recovery of leaves, twigs, etc. may be the only means of making a definite diagnosis of plant poisoning. The remains of a rat or mouse suggest secondary poisoning by strychnine or a rodenticide. Greyish-white specks of arsenic trioxide or flakes of paint may be noticed and should be removed for analysis. The colour of the stomach contents may be characteristic; copper salts impart a greenish-blue colour, chromic compounds a yellow to orange or green colour, picric and nitric acids a yellow colour, while corrosive acids such as sulphuric may blacken the stomach contents. Changes of this kind are obviously less likely to be observed in the mass of material in the rumen.

            Inflammation or, in extreme cases, corrosion of the gastrointestinal tract, is the most common finding in acute poisoning. It is impossible to do more than indicate the wide variety of poisons which can cause irritation. These include acids and alkalis, salts of heavy metals, cantharides, phenols, irritant plant poisons (from buttercups, wild arum, etc.), saponins. Arsenic should be regarded as the commenest cause of sudden death associated with finding of gastroenteritis post mortem.

            Lesions in the liver and kidneys are also frequently seen. Hepatic lesions are found, for example, in poisoning by antimony, arsenic, boric acid, iron, lead, phosphorus, selenium, thallium, chloroform and allied compounds, tannic acid, chlorinated naphthalenes, coal-tar pitch, paraffin, cotton seed and ragwort, Damage to the kidneys occurs whenever an irritant poison is absorbed and excreted in the urine. Renal lesions are also seen as a result of salt poisoning and following sulphonamide therapy. Calcium oxalate crystals are found in cases of poisoning by oxalic acid and ethylene glycol.

            The body musculature may have a peculiar colour (e.g. lead poisoning, jaundice) or may show signs of haemorrhage (warfarin and bracken poisoning, sweet clover disease).

            The procedure at autopsy depends to a large extent upon whether litigation is expected, if it is, detailed histopathological examination and/or chemical analysis may be necessary. The latter is dealt with below

            If the animal dies, a thorough necropsy should be performed and appropriate specimens collected. Lesions of poison­ing are usually less characteristic, and many toxicants cause neither gross nor microscopic lesions. However, necropsy findings may pro­vide definite clues to the nature of toxicant in some cases. Appropriate organs and tissues should be saved in 10% neutral buffered formalin for microscopic examination by a pathologist. Some intoxications can be confirmed by microscopic examination (e.g. renal oxalate crystals appear in ethylene glycol poisoning; hepatic lipidosis and bile duct proliferation occur in aflatoxicosis).

            E. Analytical Evidence The final proof of poisoning lies in the detection of a significant quantity of the toxic agent in the body of the animal; but this is not as simple as it sounds.

            The most important proof of poisoning is the detection of toxicant in the excreta (vomitus, urine, etc.) and blood during life and in the gastrointestinal contents and tissues of the body after death. It is possible to test a group of toxicants or a single toxicant but it is not possible to test all the toxicants in an ordinary laboratory. Generally, chemical analysis for toxicants should not be used alone to make a diagnosis because

1. It is possible that the animals might have died from the effects of a toxicant, and yet none may be found in the body after death because whole of the toxicant might have excreted from the body or has been detoxified into inactive metabolite and then eliminated from the body.

2. Some chemicals produce toxicosis but are present at very low levels (below detection levels) in tissues.

3. Some toxicants may not be detected in the viscera, as they have no reliable analytical procedure, e.g. organophosphates.

4. Some chemicals can accumulate to high levels in certain tissues without causing toxicosis, e.g. organochlorine insecticides residues in body fat.

5. Interactions with other agents or nutrients can inactivate a toxicant stored in the tissues. For example, mercury can form a complex with selenium and protein, resulting in a non-toxic storage form.

            The samples needed for toxicological analysis are: liver, kidney, stomach contents, intestinal contents, blood and urine. At least half a pound of each organ should be sent, or the whole if it weighs less. An ounce of blood should be sent, and all the urine available. The stomach may be tied off at each end, and sent complete with contents. When in doubt, it is always better to send too much rather than too little. The analyst will have no difficulty in disposing of excess material. In the case of small animals it is sometimes advisable to send the whole carcase.

            Each organ must be sent in a separate container clearly labelled with date, name and address of sender, particulars of organ and species and details of any preservative used. The best containers are glass jars of the 'Kilner' type but they must he carefully packed to avoid breakage, and rubber closure rings should not be used. They must not be put in the deep freeze. Polythene jars and bags are lighter and less fragile, but suffer from the disadvantages that they are permeable to many organic substances, and that the plasticizers used in their manufacture may contaminate the sample. The containers must, of course, be chemically clean, and great care must be taken to avoid accidental contamination. Jars should be sealed, and if there is any chance of legal action it is as well to have a witness to the sealing. They should be dispatched in such a way that they cannot be tampered with en route.

            Specimens should be stored in a refrigerator (or deep freeze) while awaiting dispatch to the laboratory. If it can be avoided, it is much better not to add any preservative; but there are times when the weather and the distance to the laboratory make this impossible. If a preservative has to be added it is best to use alcohol as this is rarely met with as a poison in veterinary toxicology. A sample of the alcohol used should be sent to the laboratory in a separate bottle as a control.       .

            F. Experimental evidence: Experimental feeding of suspected bait or feed may be useful when other approaches are inadequate. Experimental animals may he fed with the suspected food or the toxicant after it is separated from the viscera and symptoms exhibited are closely observed. However, the evidence derived in this manner has limited diagnostic applications and can not be relied upon in all the cases because of  

i.                    The relatively high uncertainty of reproducing field conditions;

ii.      Poor susceptiblity of some experimental species to some groups of toxicants, i.e. rabbits to belladonna leaves (atropine), and pigeons to opium.

            G. Therapeutic evidence (Response to treatment): Response to a test dose of specific antidote in an intoxicated animal may confirm a clinical diagnosis. For example, clinical improvement (reduced salivation, dyspnoea, convulsions, etc.) after administration of atropine is an evidence of anticholinesterase (organophosphorus and carbamate insecticides) poisoning.