Studies on magnesium ammonium phosphate urolithiasis in dogs

Abstract

This research study is essentially concerned with the etiology of magnesium ammonium phosphate urolithiasis in dogs, particularly the role of bacterial infection of the urinary tract on the formation of calculi* The problem was investigated from four aspects by carrying out} I* a clinical and bacteriological study of dogs, cats and sheep with urolithiasis) II* a study of the structure of canine calculi) III* tests on bacteria isolated from dogs with urolithiasis) IV* attempts to reproduce calculi experimentally in vitro in canine urine and in vivo in dogs.I. URINARY TRACT INFECTION IN RELATION TO UROLITHIASIS IN DOGS AND OTHER ANIMALS A review of the literature showed that other workers had noted that magnesium ammonium phosphate calculi were frequently associated with bacterial infection of the urinary tract in dogs and man* Differing opinions were expressed on infection in cats and sheep with urolithiasis. Staphylococci were recognised as the main type of organism recovered from dogs but workers studying urolithiasis in man have found a wider variety of organisms involved.In the present study urinary tract infection was present in 82% of dogs with magnesium ammonium phosphate calculi and in 22% of dogs with calculi composed of calcium salts. Infection was absent from all dogs with cystine calculi.In 44 cases of magnesium ammonium phosphate calculi staphylococci were isolated on 31 occasions, streptococci on 7, Proteus species on 3 and other organ!sue were found on 5 occasions. In 8 cases the urine was sterile.Crystals were removed from 43 magnesium ammonium phosphate calculi and sections were prepared of the remaining organic matrices. In 41 of these sections bodies resembling bacterial cocci were present. In 33 instances these calculi were associated with staphylococcal or streptococcal infection of urine, while in the remaining cases the urine was either sterile or infected with organisms of a different typo.Dogs with urolithiasis were treated by surgical removal of calculi and antibiotic therapy. Their post-operative progress was followed by clinical and radiological exaiainations.In animals with magnesium ammonium phosphate stones at the initial episode, recurrence of calculi occurred in 30% of cases while in dogs with calculi composed of calcium salts or cystine the recurrence rates were 77% and 75% respectively. At follow-up examination 11 dogs were infected with staphylococci and 9 of these had recurrent calculi composed of magnesium ammonium phosphate.These studies confirmed the association between staphylococcal infection and magnesium ammonium phosphate urolithiasis in dogs. Bacteria did not appear to be involved in the deposition of magnesium aamoniuis phosphate crystals in the urinary tracts of 10 cuts or 4 sheep.II. PHYSICAL CHARACERISTICS OF CANINE URINARY CALCULI Calculi retrieved from dogs with urolithiasis were weighed and their shape recorded. Thin sections of the stones were prepared and the internal structure examined maeroscopieaily and microradiographically. The mean weight of magnesium ammonium phosphate calculi from female dogs was 19.87g and from male animals 0.98g.The number of magnesium ammonium phosphate calculi and their shape, size and surface texture appeared to be inter-related. Single calculi were usually of a spherical shape while large multiple calculi tended to be tetrahedra.Examination of the internal structure of magnesium ammonium phosphate calculi Use other side if necessary. shoved that nuclei were occasionally present but did not seem to be ait mportant cause of urolithiasis* Many of the calculi were composed of bands of crystals of alternating composition. Central fissures were also noted in several calculi.III. PROPERTIES OF BACTERIA ASSOCIATED WITH MAGNESIUM AMMONIUM PHOSPHATE UROLITHIASIS. Review of the literature showed that earlier workers considered the production of urease by bacteria and its action in raising urinary pH was important in the etiology of urolithiases by reducing the solubility of magnesium ammonium phosphate in urine. Some bacteria can produce phosphatase and the possible effect on calculi was studied. Urease was produced by 33 out of 34 strains of staphylococci and by all 3 strains of Proteus tested. Four strains of streptococci and 2 strains of E. coli were urease negative. Phosphatase was produced by 33 out of 34 strains of staphylococci but not by the other organisms isolated from dogs with calculi. Urease and phosphatase could influence the solubility of magnesium ammonium phosphate in urine but neither enzyme was produced by all staphylococci isolated from dogs with calculi.Tests for the production of coagulase, haemolysis and pigment production were carried out on 34 strains of staphylococci. Thirty-one strains produced coagulase, 29 strains haemolysed sheep blood, 8 strains haemolysed horse blood and 2 strains produced golden pigment.IV. EXPERIMENTAL STUDIES ON UROLITHIASIS The literature on experimental production of calculi in vitro and in vivo was reviewed. It was found that dogs have been seldom used in experimental work.When calculi were placed in sterile canine urine in vitro they became smaller and when placed in urine infected with staphylococci or Proteus organisms little change occurred in the calculi but there was a heavy deposit of magnesium ammonium phosphate crystals from the urine.Experimental bladder infection with staphylococci was established in 3 dogs and 1 of these developed a magnesium ammonium phosphate calculus.As a result of these investigations it was concluded that urinary tract infection with staphylococci is an important factor in magnesium ammonium phosphate urolithiasis. The production of urease by bacteria leads to elevation of the urinary pH and causes deposition of magnesium ammonium phosphate crystals but the mechanism by which these crystals aggregate to form calculi was not established.