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This article was published in 1963
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INSTITUTE OF INSPECTORS OF STOCK OF N.S.W. YEAR BOOK.
Recent Concepts of the Development and Control of Ruminant Urolithiasis
I. L. JOHNSTONE, B.V.Sc., Associate Professor in Wool Technology, The University of New South Wales
Urolithiasis is the name given to urinary calculi, frequently referred to as "sand", "gravel" or "stones", and to fine precipitated deposits forming in the urinary tract, which may cause obstruction to urinary flow, and lead to rupture of the bladder or "water belly".
These deposits may be in the form of a single large calculus, a number of discrete smaller stones, a gritty sludge resembling dry ice in consistence or a combination of these types. Unless partial or complete blockage occurs there is no apparent ill effect on the health of the animal.
Blockage occurs most frequently in the urethral process and in the sigmoid flexure of the penis. Less frequently it may occur at the pelvic flexure, in the neck of the bladder and more rarely in the pelvis of the kidney. Urolithiasis may be accompanied by a collection of gritty incrustations on the preputial hairs. This may be indicative of the syndrome precipitating the disease but is frequently seen in apparently normal wethers.
TYPES OF CALCULI
Calculi may vary widely in composition but under Australian conditions the three major types consist of (i) carbonates of calcium and magnesium in flock sheep (ii) silicates in pen fed rams and (iii) organic material as in the case of "Clover Stones". In the United States of America phosphatic calculi are a serious problem in sheep and cattle in feed-lots while siliceous calculi are frequently reported under range conditions. Less commonly, urates, oxalates and xanthin have been incriminated in sheep and other animals.
Differences in composition are associated with differences in diet and other predisposing factors.
The carbonate type calculi occur most frequently on native pastures particularly in western New South Wales, western Queensland and in the eastern agricultural areas of Western Australia. They are of the size and shape of small shot, hard, yellow to greyish and occasionally gilded in colour, as in a recent occurrence in New England. In Western Australia and South Australia weaners and two-tooths are frequently affected, but in New South Wales and Queensland, losses are mainly restricted to older wethers. Affected sheep are usually in good condition and losses generally commence in the late Autumn in Queensland and Western Australia where conditions are dry, but in western New South Wales heavy losses extend into the late Spring after a good herbage Winter.
The carbonate type calculi have frequently been associated with oxalate containing plants such as Parakeelia (Calandrinia bolonnensis).
Siliceous calculi are associated with an acid urine. They are usually less regular, like grains of wheat or mulberry shaped, friable and white in colour but may be brown to black. They are often found in the renal pelvis and are thought to originate in the kidney, and obstruction may even occur in the ureter. These calculi are composed mostly of silica and are associated with the ingestion of plants high in silicon. Blady grass (Imperata cylindrica) has been incriminated in three cases in cows in Queensland. Silica occurs both in plant tissues and free in the plant environment and can be readily detected in the rumen of sheep grazing on improved pastures on the Southern Tablelands.
Little is known of the formation of the organic type "Clover Stone" reported mainly from Western Australia. The calculus material is sulphur yellow in colour, moist, soft and easily broken up and largely confined to the kidney but associated with yellow incrustations on the preputial hairs. These calculi are thought to be composed mostly of inflammatory exudates resulting from an irritant substance arising from extensive grazing on Dwalganup Subterranean Clover.
Phosphatic calculi appear to be less common in Australia than in the United States of America where they are a serious problem of feed-lots. Under these conditions they consist of a gritty sludge of micro-calculi with a crushed ice appearance. These calculi have been provoked experimentally on a high concentrate diet to which potassium phosphate has been added. It is possible that some of the calculi in pen fed rams are of this type, but phosphate has only been encountered occasionally and in small quantities in calculi analysed.
In America losses from phosphatic and siliceous calculi occur in rapidly growing animals in late Autumn but principally in the Winter. They occur both in male and female sheep and cattle but, because of the shorter, less constricted outlet from the bladder in females, urolithiasis is seldom detected in them except on post-mortem examination.
ANATOMICAL ASPECTS OF UROLITHIASIS
The site of formation of calculi in the urinary tract has not been satisfactorily established. Phosphatic, siliceous and organic deposits have been frequently observed in the pelvis of the kidney but may be restricted to the bladder and urethra. Micro-calculi of phosphate crystals have been observed in the collecting tubules of the kidney and plaques, considered as possible nuclei for calculus formation, have been described as attached to the mucosa of the papillae of the renal pelvis. The sludge of phosphatic micro-calculi may occur in the renal pelvis or in the bladder. These micro-calculi may aggregate in the bladder, or may continue to pass out as a sludge and accumulate in the narrower canal of the urethral process or in the bends of the sigmoid flexure, causing partial or complete blockage. The urethral process may become necrotic and slough off, re-establishing normal urination without the development of obvious clinical symptoms.
THE NATURE AND FORMATION OF CALCULI
Although some calculi, such as the "Clover Stone", consist almost entirely of organic matter, generally they consist of two fractions, an organic fraction of mucoprotein and an inorganic fraction of carbonate, silicate or phosphate depending on the individual predisposing factors operating.
In the case of a single "stone" or a series of hard discrete "stones", the calculus is built up in a series of concentric layers with the inorganic fraction enclosed in a matrix of mucoprotein within each layer. The existence of a nucleus has been presumed but not adequately established in all types of calculus. On the other hand phosphatic calculi may consist of an aggregation of micro-calculi each with the phosphate crystal enclosed in an envelope of mucoprotein.
The importance of the mucoprotein fraction is now generally accepted but the nature of this mucoprotein has not been adequately defined. Urolithiasis appears to be accompanied or preceded by an increase in serum mucoprotein.
Histochemical techniques have revealed the simultaneous appearance of an abnormal increase in mucopolysaccharide material within the cells of the proximal and distal convoluted tubules, on the brush borders of the proximal convoluted tubules, as cast material within the lumina of the collecting tubules and on the surface of the transitional epithelial cells of the renal pelvis and urinary bladder. A material staining similarly with periodic acid Schiff Reagent has been observed in the micro-calculi of the urine sediment and in the larger aggregates of calculi material. These observations suggest that the mucoid material of the calculi may be pre-renal in origin, and the mechanism which triggers off calculus formation.
Calculi and, in particular, phosphate calculi can be formed very quickly, deaths occurring within 15 days after changing on to a calculi provoking diet. Most deaths occur in the first forty days, and losses decrease thereafter although when experimental sheep have been killed after 120 days on a calculi-provoking ration much calculous material is still present.
PREDISPOSING FACTORS
The predisposing factors thought to be associated with urolithiasis are:—
(1) A high concentrate to roughage ratio of 4:1 (or greater) particularly when potassium phosphate is added to the diet.
(2) A calcium phosphate ratio of less than 1:1.
(3) A stress factor such as a sudden cold snap leading to reduced water intake and a concentration of the urine.
(4) A sudden, perhaps short term, change in the reaction of the urine from alkaline to acid, or acid back to alkaline, associated with an intermittent feed intake or a change in ration.
(5) The ingestion of oxalate and silicon containing plants.
(6) Factors causing reduction in the diameter of the urethra or urethral spasm, such as early castration and sex hormones.
(7) A reciprocal relationship between phosphate and magnesium excretions by the kidney and possibly metabolic interactions of other electrolytes.
Attempts to induce urolithiasis in both sheep and cattle have been relatively successful in the case of phosphatic calculi, and certain diets are now spoken of as "calculi-provoking" diets. Forced reduction of water intake has not been rewarding and attempts to produce carbonate calculi by the feeding of oxalates has also been unsuccessful.
The most successful method has been to change rapidly growing sheep from a diet of lucerne hay or lucerne cubes on to a high concentrate diet (4:1 or even 8:1) to which 2.5% potassium mono-hydrogen phosphate has been added. The importance of the initial diet does not seem to have been investigated but could be of importance. The rations mainly used include dried beet pulp, linseed meal, oats, wheat and wheat straw as the roughage content. This diet is very low in calcium.
Using the basic diet and increasing only the phosphate had little effect on the incidence of urolithiasis; increasing potassium increased the incidence seven times and adding both potassium and phosphate, twenty-eight times. The inclusion of both potassium phosphate and beet pulp resulted in the highest incidence.
Results of feeding experiments are rather confusing but, in general, in America the incidence of calculi is greater on diets including beet pulp; white maize as opposed to yellow maize; soya bean meal or bran. In Australia lucerne is frequently incriminated. Many calculi-provoking rations are fed in pellet form and there is some evidence that the incidence of calculi is inversely proportional to the size of the pellet.
Because of the association with white maize, dry feed, or a late Autumn/Winter incidence with some calculi, vitamin A deficiency has been suspected as a predisposing factor. All attempts to substantiate this have failed.
The ratio of calcium to phosphorus has been frequently incriminated in urolithiasis but published results are confusing. One very neat experiment showed that when both elements were low in the diet (0.27%) the incidence was low. As phosphorus was increased to 0.54% the incidence increased but was again decreased when the calcium content was also elevated to 0.54%. However when the phosphorus content of the ration was increased to 0.8%. elevating the calcium to 0.8% had less effect in controlling the incidence of urolithiasis. Phosphorus in calculi is usually associated with calcium, magnesium and sometimes aluminium. Rarely is there an association with silica, siliceous calculi being associated with acid urine and phosphatic calculi with alkalinity of the urine. However there is an unpublished report from Glenfield of a calculus with alternate layers of silicate and oxalate.
A ration of lucerne supplemented with excessive amounts of calcium and magnesium carbonates has been shown to predispose to calculi, but an increase in the calcium content of the diet did not increase the excretion of calcium but did increase the excretion of mucoproteins.
The ingestion of oxalate is known to upset calcium metabolism and free oxalate has been observed in kidney sections. It is possible that this oxalate may be excreted as carbonate and so account for the presence of carbonate in this type of calculi.
There is substantial evidence that urolithiasis is associated with a reduced intake of water although a forced reduction in water intake has failed to precipitate the condition. The reduced water intake is generally self-inflicted and associated with such external factors as a sudden cold snap or the ingestion of plants with a high water content. These observations have been used to develop methods of prevention and control of urolithiasis by adding salt to the diet to increase water intake and so prevent concentration of the urine. Diets containing as much as 10% salt have been used experimentally with highly successful results. A salt content of this order is likely to reduce feed intake and so be undesirable particularly in the feeding of stud rams.
Salt can be fed in the ration, included in pellets, supplied as a lick or in special circumstances added to the drinking water. Work in Australia has shown that sheep can tolerate up to 1.3% in the drinking water and this method may have some application in special circumstances. With concentrate feeding, 2% to 5% salt could be mixed in the ration, and feed intake is unlikely to be reduced at these levels. The higher levels can be used in cattle feeding.
It should be mentioned that most of the experimental work with salt to reduce the incidence of urolithiasis has been associated with siliceous and phosphatic calculi and may not apply in the case of calculi containing carbonates of calcium and magnesium. However, salt has been used on several occasions in New South Wales with apparent success.
When sheep are fed in pens once a day a sudden marked post-prandial change in urine from an alkaline to an acid reaction has been observed. This change is of short duration. It has not been established whether this change is associated with a stop-start mechanism in the laying down of concentric rings in urinary calculi. However where calculi are of frequent occurrence in feeding stud rams, shorter interval feeding might be considered.
Urethral occlusion in feed-lot lambs implanted with 12 mg to 15 mg stilboestrol is common in the United States. These cases are characterised by rupture of the bladder following occlusion of the urethra. In some cases, on post-mortem examination, a soft colourless material, having a fine grittiness and identified as mucoprotein, has been found occluding the urethral process or located in the region of the sigmoid flexure. In other cases no extraneous material has been found. There is one report of inflammation of the urethra, marked enlargement of the secondary sex glands, particularly the seminal vesicles and bulbo-urethral glands, is also found. There is a recent report of obstruction of the urethra in adult male mice, suddenly removed from breeding colonies, and in which the obstructing material was thought to arise from the secondary sex glands.
Magnesium metabolism may also be concerned in the development of phosphate calculi. High serum magnesium has been reported in lambs affected with urinary calculi and more recently a reciprocal relationship between urinary excretion of phosphorus and magnesium has been established. As the excretion of magnesium decreases, the excretion of phosphorus increases, and it has been suggested that the average excretory levels of these two elements could be used to forecast treatments, which could be calculo-genic, prior to the development of clinical cases.
PREVENTION OF UROLITHIASIS:
Summarising the factors associated with predisposition to urolithiasis suggests recommendations which might be made for the prevention of urinary calculi. This is difficult because of the differences in the nature of urinary calculi.
In lot feeding of lambs and in pen feeding stud rams the concentrate portion of the ration should be reduced to the lowest practical level, particularly when pellets are used. The calcium : phosphorus ratio should be in the vicinity of 1:1 or with a slight excess of calcium and keeping the phosphorus content of the diet below 0.5%. Careful enquiry should be made before supplying pre-mixed mineral supplements.
Stress factors which might lead to a reduced water intake and concentration of the urine should be avoided if possible. Precautions against this might be taken by including from 2 to 5% salt in the ration, provided adequate palatable water is available. Stilboestrol implants should not be used without an appreciation of the risks involved.
Outbreaks under field conditions may be more difficult to prevent, and experimental evidence in support of preventive measures is not available. When sheep are grazing oxalate-containing plants, particularly in the late Autumn and Winter consideration could be given to the use of salt as a lick. In the case of siliceous or phosphatic calculi, calcium carbonate might be included but this would appear to be contra-indicated in the case of calculi containing carbonates of calcium and magnesium.
The sudden appearance of gritty incrustations on the preputial hairs should be regarded with suspicion although the full significance of this clinical sign is not yet known. Further information on the importance of early castration is also needed before any recommendations can be made.
TREATMENT
Treatment of clinical cases, particularly rams, is generally unsatisfactory. Recurrence after surgical removal of the calculus from the urethra is a distinct possibility. Treatment has been aimed in two main directions; changing the pH of the urine in the reverse direction to the existing status, and the use of drugs to dilate the urethral canal or relieve a sphincter type spasm.
Calculi containing phosphates or carbonates of calcium and magnesium occur in alkaline urine and daily drenching for 7 days with ½ oz. ammonium chloride and the supplying of ample water will produce an acid urine. In most cases sheep will cease to eat and starvation alone will produce an acid urine, Where the calculi consist of hard discrete "stones" this type of treatment is unlikely to be highly successful.
In the dog a hyaluronidase preparation (9 mg Rondase) has been used successfully to release a urethral calculi. In cattle there is a report of the use of amino-promazine to relieve sphincter spasm and allow urination. This is reported to permit manipulation and crushing of the calculi through the skin. Large quantities of water were administered at the same time to facilitate flushing.
It is not generally appreciated that it is possible to pass fine surgical tubing (one millimetre diameter) into the bladder of a sheep after removal of the urethral process. This is useful in the case of a fine deposit and when blockage is not complete and permits emptying and flushing of the bladder.
However treatment of urolithiasis is not generally satisfactory and prevention appears to offer more possibilities than cure.