Renal tubular acidosis (RTA) is a rare disease of large animals that is characterized by normal glomerular function but abnormal tubular function. RTA should be suspected whenever there is a hyperchloremic strong ion (metabolic) acidosis with no discernible extrarenal cause; a common extrarenal cause of hyperchloremic strong ion acidosis is aggressive intravenous administration of 0.9% NaCl.
Four major types of tubular functional defect exist: 1) renal diabetes insipidus, where the tubules do not respond to antidiuretic hormone; 2) Fanconi’s syndrome, which is a genetic defect in humans related to the tubular resorption of glucose, various amino acids, urate, and phosphate; 3) distal RTA (type I), which is a defect in the ability to secrete hydrogen ions in the distal convoluted tubules against a concentration gradient;1 and 4) proximal RTA (type II), which is characterized by decreased bicarbonate reabsorption in the proximal convoluted tubules.2 Reabsorption of bicarbonate requires energy, therefore disease processes that lead to proximal tubular damage have the potential to result in proximal RTA.3 Other causes of RTA have been described in humans but have not been documented in large animals. The urine of animals with proximal RTA (type II) is acidic, whereas the urine of animals with distal RTA (type I) is very alkaline, regardless of the serum bicarbonate concentration.
Only a few cases of RTA have been documented in horses, and these have been predominantly of the distal type. Horses with distal RTA (type I) have a profound strong ion acidosis due to hyperchloremia (normal anion gap metabolic acidosis), accompanied by an alkaline urine pH (typically > 8.0) and increased fractional clearance of sodium.1 A practical diagnostic test for distal RTA involves examining the ability of the distal convoluted tubules to excrete hydrogen ions by the oral administration of ammonium chloride (0.1 g/kg BW in 6 L of water via nasogastric tube). Inability to achieve an acidic urine (pH <6.5) after oral ammonium chloride administration is consistent with a diagnosis of distal RTA (type I). A practical diagnostic test for proximal RTA (type II) is measuring the change in urine Pco2 during oral or intravenous sodium bicarbonate administration.2 Normally, urine and plasma Pco2 are similar but, during bicarbonate diuresis, urine Pco2 becomes greater than plasma Pco2. The Pco2 gradient during intravenous sodium bicarbonate administration is therefore measured; one horse with proximal RTA developed a urine to plasma Pco2 gradient of 29 mmHg during bicarbonate loading.2
Treatment of horses with distal RTA (type I) has been symptomatic and focuses on oral or intravenous administration of sodium bicarbonate.1 Spontaneous recovery has been reported in horses. Treatment of horses with proximal RTA (type II) is uncertain.2
Interstitial nephritis is rarely recognized as a cause of clinical disease in farm animals although it is a frequent postmortem finding in some species. Interstitial nephritis may be diffuse or have a focal distribution. In calves, focal interstitial nephritis (white-spotted kidney) is a common incidental finding at necropsy but does not present as a clinical urinary tract disease.1 Focal interstitial nephritis of cattle is not associated with leptospirosis or active bacterial infection.2 In pigs, diffuse interstitial nephritis is observed following infection by Leptospira sp. and is important clinically because of the resultant destruction of nephrons that occurs. The kidney is an important reservoir for Leptospira spp. in other species, particularly cattle, but renal disease is not a common clinical problem in carrier animals.3
Chronic interstitial fibrosis is a common postmortem finding in horses suffering from chronic renal failure.4 This is believed to represent an end-stage condition rather than primary interstitial disease. The initiating cause of the renal disease is usually not evident but most cases are believed to begin with acute tubular nephrosis. Horses with chronic interstitial nephritis have the clinical syndrome of chronic renal failure with uremia.
Embolic lesions in the kidney do not cause clinical signs unless they are very extensive, in which case septicemia may be followed by uremia. Even though embolic nephritis may not be clinically evident, transient proteinuria and pyuria may be observed if urine samples are examined at frequent intervals.
Embolic suppurative nephritis or renal abscess may occur after any septicemia or bacteremia when bacteria lodge in renal tissue.
Emboli may originate from localized septic processes such as:
Bacterial emboli localize in renal tissue and cause the development of focal suppurative lesions. Emboli can block larger vessels and cause infarction of portions of kidney, the size varying with the caliber of the occluded vessel. Infarcts are not usually so large that the residual renal tissue cannot compensate fully and they usually cause no clinical signs. If the urine is checked repeatedly, the sudden appearance of proteinuria, casts, and microscopic hematuria, without other signs of renal disease, suggests the occurrence of a renal infarct. The gradual enlargement of focal embolic lesions leads to the development of toxemia and gradual loss of renal function. Clinical signs usually develop only when multiple emboli destroy much of the renal parenchyma, or when there is one or more large infected infarcts.
Usually there is insufficient renal damage to cause signs of renal disease. Signs of toxemia and the primary disease are usually present. The kidney may be enlarged on rectal examination. Repeated showers of emboli or gradual spread from several large, suppurative infarcts may cause fatal uremia. Spread to the renal pelvis may cause signs similar to pyelonephritis. Large infarcts may cause bouts of transient abdominal pain.
Hematuria and pyuria are present but microscopic examination may be necessary to detect these abnormalities when the lesions are minor. Proteinuria is present but is also normally present in neonatal animals in the first 30–40 hours of life. Culture of urine at the time when proteinuria occurs may reveal the identity of the bacteria infecting the embolus. Hematology usually reveals evidence of an acute or chronic inflammatory process.
In animals that die of intercurrent disease the early lesions are seen as small gray spots in the cortex. In later stages these lesions may have developed into large abscesses, which may be confluent and in some cases extend into the pelvis. Fibrous tissue may surround long-standing lesions and healed lesions consist of areas of scar tissue in the cortex. These areas have depressed surfaces and indicate that destruction of cortical tissue has occurred. Extensive scarring may cause an obvious irregular reduction in the size of the kidney.
General information on treatment of urinary tract infections is presented in the section on treatment of urinary tract diseases. Antimicrobials should be selected on the basis of quantitative urine culture and susceptibility testing. In treating septicemic neonatal animals, particular care must be taken to avoid the use of potentially nephrotoxic drugs. Antibiotic treatment should be continued for a fairly lengthy period (7–14 d). In embolic nephritis, the primary disease must be controlled as well as the renal disease to prevent recurrence of the embolic lesions. In neonatal animals this may involve treatment for septic shock. The urine culture should be repeated at intervals after treatment is completed to insure that the infection has been completely controlled.
Differentiation from pyelonephritis is difficult unless the latter is accompanied by signs of lower urinary tract infection such as cystitis or urethritis. The kidney is enlarged in both conditions and the findings on urinalysis are the same when embolic nephritis invades the renal pelvis. Many cases of embolic nephritis go unrecognized clinically because of the absence of overt signs of renal involvement.
Severely dehydrated neonatal animals may experience prerenal uremia and are susceptible to ischemic tubular nephrosis. The presence of other signs of sepsis should increase suspicion of the presence of embolic nephritis.
The sudden occurrence of bouts of acute abdominal pain in some cases of renal infarction may suggest acute intestinal obstruction, but defecation is usually unaffected and rectal examination of the intestines is negative.
Pyelonephritis usually develops by ascending infection from the lower urinary tract. Clinically it is characterized by pyuria, hematuria, cystitis, ureteritis, and suppurative nephritis.
Pyelonephritis may develop in a number of ways:
• Secondary to bacterial infections of the lower urinary tract
• Spread from embolic nephritis of hematological origin such as septicemia in cattle associated with Pseudomonas aeruginosa
• Specific pyelonephritides associated with C. renale, Corynebacterium pilosum (formerly C. renale type 2) and Corynebacterium cystitidus (formerly C. renale type 3) in cattle and Corynebacterium suis in pigs
• Secondary to anatomical abnormalities of the kidneys or distal structures permitted ascending infection of the kidney
• In association with nephroliths, although whether the nephrolith or the pyelonephritis occurred first is uncertain.
Pyelonephritis develops when bacteria from the lower urinary tract ascend the ureters and become established in the renal pelvis and medulla. Bacteria are assisted in ascending the ureters by urine stasis and reflux of urine from the bladder. Urine stasis can occur as a result of blocking of the ureters by inflammatory swelling or debris, by pressure from the uterus in pregnant females and by obstructive urolithiasis. Initially the renal pelvis and medulla are affected because they are relatively more hypoxic and localized tissue hypertonicity depresses the phagocytic function of leukocytes. Infection in advanced cases may extend to the cortex. Pyelonephritis causes systemic signs of toxemia and fever and, if renal involvement is bilateral and sufficiently extensive, uremia develops.1 Pyelonephritis is always accompanied by pyuria and hematuria because of the inflammatory lesions of the ureters and bladder.1
Pyelonephritis in cattle due to C. renale used to be very common but clinical disease has decreased markedly, with the majority of pyelonephritis cases in cattle now being due to E. coli. The reason for the decrease in C. renale isolation from clinical cases is unclear but is probably related to a change in diet towards concentrates with an associated decrease in urine pH; other potential reasons could be the widespread use of beta-lactam antibiotics and the marked decrease in urethral catheterization in order to obtain a urine sample in cows suspected to be ketotic. C. renale attaches most efficiently to well-differentiated epithelial cells (transitional epithelium cells), with poor attachment at pH less than 6.8, a rapid increase in adhesion from 6.8 to 7.6, and a high rate of attachment at pH above 7.6.2 C. renale used to be typed as 1, 2, and 3, but the latter two have been renamed C. pilosum (formerly C. renale type 2) and C. cystitidus (formerly C. renale type 3), with apparent type differences in their preferred colonization site in the vagina and urethra.2,3 Uropathogenic strains of E. coli also attach to epithelial cells by a type 1 pili, with the optimal pH for attachment of 6.0. Attachment of bacterial to urinary epithelium appears to be an important virulence attribute.
Transmission of C. suis in pigs may occur after mating with infected boars, because many boars carry C. suis in their preputial sac fluid. Field observations suggest that slight trauma at breeding, especially in small gilts, may be an important factor in transmission.4
The clinical findings in pyelonephritis vary between species. In sows there may be an initial period during which a vaginal discharge is noted but most affected animals die without premonitory illness. Characteristically, affected pigs will lose weight and eventually become emaciated.5 The disease in cattle is described in detail in the section on bovine pyelonephritis.
The disease in horses is often chronic, although acute disease occurs. Gross hematuria is recognized in some horses with pyelonephritis, although this is not a common finding.5 Ultrasonographic examination of the kidneys can confirm the diagnosis, based on the presence of abnormally shaped kidneys with loss of the corticomedullary gradient, hypo- or hyperechoic abnormalities in the renal cortex, and increased echogenicity. These findings should prompt examination of the urine for leukocytes, casts, protein, and bacteria.
Erythrocytes, leukocytes, and cell debris are present in the urine on microscopic examination and may be grossly evident in severe cases, particularly in horses.5 Quantitative urine culture is necessary to determine the causative bacteria.
The kidney is usually enlarged and lesions in the parenchyma are in varying stages of development. Characteristic lesions are necrosis and ulceration of the pelvis and papillae. The pelvis is usually dilated and contains clots of pus and turbid urine. Streaks of gray, necrotic material radiate out through the medulla and may extend to the cortex. Affected areas of parenchyma are necrotic and may be separated by apparently normal tissue. Healed lesions appear as contracted scar tissue. Infarction of lobules may also be present, especially in cattle. Histologically the lesions are similar to those of embolic nephritis except that there is extensive necrosis of the apices of the papillae. Necrotic, suppurative lesions are usually present in the bladder and ureters.
General principles of treatment of urinary tract infections are presented above in the section on treatment of urinary tract disease. A specific treatment for severe asymmetric pyelonephritis is unilateral nephrectomy, but this should only be done in nonazotemic animals. An overlooked component of treatment is alteration in urinary pH, which will affect the ability of the bacteria to attach to epithelial cells. As a generalization, C. renale attaches best in alkaline urine and E. coli attaches best in acidic urine. Refer also to the section on bovine and porcine cystitis pyelonephritis.
The presence of pus and blood in the urine may suggest cystitis or embolic nephritis as well as pyelonephritis. It may be difficult to distinguish between these diseases but renal enlargement or pain on rectal palpation of the kidney indicates renal involvement. Ultrasonographic changes associated with pyelonephritis include a dilated renal collecting system, renal or ureteral calculi, increased echogenicity, loss of corticomedullary echogenicity and subjective enlargement of the kidney with acute disease or a small irregular kidney with chronic disease.5,6 Parenchymal hyperechogenicity can be caused by tubular degeneration and replacement fibrosis.
Hydronephrosis is a dilatation of the renal pelvis with progressive atrophy of the renal parenchyma. It occurs as a congenital or an acquired condition following obstruction of the urinary tract. Any urinary tract obstruction can lead to hydronephrosis but the extent and duration of the obstruction are important in determining the severity of the renal lesion. Urinary tract obstructions that are chronic, unilateral, and incomplete are more likely to lead to hydronephrosis. Acute obstructions of bladder or urethra that are corrected promptly are not usually associated with significant kidney damage. As a result, recurrence of the obstruction rather than renal failure is the major sequel to urolithiasis in ruminants. In cases of acute complete obstruction the clinical picture is dominated by signs of anuria, dysuria, or stranguria.
Chronic or partial obstructions cause progressive distension of the renal pelvis and pressure atrophy of the renal parenchyma. If the obstruction is unilateral, the unaffected kidney can compensate fully for the loss of function and the obstruction may not cause kidney failure. Unilateral obstruction may be detectable on palpation per rectum of a grossly distended kidney. Chronic bilateral obstructions, although they are rare in large animals, can cause chronic kidney failure. Hydronephrosis and chronic renal failure have been recorded in a steer suffering from chronic partial obstruction of the penile urethra by a urolith.1 Partial obstruction of the ureters by papillomas of the urinary bladder has been recorded in a series of cows.2 Compression by neoplastic tissue in cases of enzootic bovine leukosis may also cause hydronephrosis. Ultrasonography can be used as an aid to diagnosis.2
Primary tumors of the kidney are uncommon. Carcinomas occur in cattle and horses and nephroblastomas occur in pigs. Enlargement of the kidney is the characteristic sign; in cattle and horses neoplasms should be considered in the differential diagnosis of renal enlargement. In pigs, nephroblastomas may reach such a tremendous size that they cause visible abdominal enlargement. Renal adenocarcinomas are very slow-growing but are not usually diagnosed until the disease is well advanced. The gross and histological descriptions of a series of primary renal cell tumors in slaughter cattle has been recorded.1 In horses, the most common signs are weight loss, reduced appetite and intermittent bouts of abdominal pain.2,3 Some affected horses have massive ascites, hemoperitoneum, or hematuria.2,3 Metastasis of the tumor to the axial skeleton can result in lameness, which can be the clinical abnormality that is recognized first.4,5 The tumor can also metastasize to the lungs and mouth.5,6 Masses on the left kidney of horses are usually readily palpable on rectal examination.3 Horses with renal carcinoma can have clinically apparent periods of hypoglycemia.7 Hypoglycemia is confirmed by measurement of serum glucose concentration and is attributable to production of insulin-like growth factor by the neoplastic tissue.8 Ultrasonographic examination of the kidney, and renal biopsy, confirm the diagnosis.
Metastatic neoplasms occur fairly commonly in the kidney, particularly in enzootic bovine leukosis, but they do not cause clinical renal disease. Tumor masses may be palpable as discrete enlargements in the kidneys of cattle or may involve the kidney diffusely, causing generalized enlargement of the kidney.
1 Kelley LC, et al. Vet Pathol. 1996;33:133.
2 Von Mol KAC, Fransen JA. Vet Rec. 1986;119:238.
3 West HJ, et al. Equine Vet J. 1987;19:548.
4 Rhind SM, Sturgeon B. Equine Vet Educ. 1999;11:171.
5 Rumbaugh ML, et al. Equine Vet J. 2003;35:107.
6 Rhind SM, et al. J Comp Pathol. 1999;120:97.
Diseases of the bladder, ureters and urethra
Inflammation of the bladder is usually associated with bacterial infection and is characterized clinically by frequent, painful urination (pollakiuria and dysuria) and the presence of blood (hematuria), inflammatory cells and bacteria in the urine.
Cystitis occurs sporadically as a result of the introduction of infection into the bladder when trauma to the bladder has occurred or when there is stagnation of the urine. In farm animals the common associations are:
• Contaminated catheterization
• As a sequel to paralysis of the bladder. A special case of bladder paralysis occurs in horses grazing sudax or Sudan grass and in horses with equine herpesvirus myoencephalopathy.
In the above cases, the bacterial population is usually mixed but predominantly E. coli. There is also the accompaniment of specific pyelonephritides in cattle and pigs, associated with C. renale and Eubacterium suis, respectively. Many sporadic cases also occur in pigs, especially after farrowing. Common isolates from these are E. coli, Streptococcus, and Pseudomonas spp. Corynebacterium matruchotii causes encrusted cystitis in horses.1
Enzootic hematuria of cattle resembles but is not a cystitis.
Bacteria frequently gain entrance to the bladder but are usually removed by the flushing action of voided urine before they invade the mucosa. Mucosal injury facilitates invasion but stagnation of urine is the most important predisposing cause. Bacteria usually enter the bladder by ascending the urethra but descending infection from embolic nephritis may also occur.
The urethritis that usually accompanies cystitis causes painful sensations and the desire to urinate. Urination occurs frequently and is accompanied by pain and sometimes grunting; the animal remains in the urination posture for some minutes after the flow has ceased, often manifesting additional expulsive efforts. The volume of urine passed on each occasion is usually small. In very acute cases there may be moderate abdominal pain, as evidenced by treading with the hindfeet, kicking at the belly and swishing with the tail, and a moderate febrile reaction. Acute retention may develop if the urethra becomes blocked with pus or blood, but this is unusual.
Chronic cases show a similar syndrome but the signs are less marked. Frequent urination and small volume are the characteristic signs. In chronic cases, the bladder wall may feel thickened on rectal examination and, in horses, a calculus may be present. In acute cases no palpable abnormality may be detected but pain may be evidenced. Endoscopic examination of the bladder of affected horses reveals widespread inflammation of the cystic mucosa and occasionally the presence of a cystic calculus.
Blood and pus in the urine is typical of acute cases and the urine may have a strong ammonia odor. In less severe cases the urine may be only turbid and in chronic cases there may be no abnormality on gross inspection. Microscopic examination of urine sediment will reveal erythrocytes, leukocytes, and desquamated epithelial cells. Quantitative bacterial culture is necessary to confirm the diagnosis and to guide treatment selection.
Acute cystitis is manifested by hyperemia, hemorrhage and edema of the mucosa. The urine is cloudy and contains mucus. In subacute and chronic cases the wall is grossly thickened and the mucosal surface is rough and coarsely granular. Highly vascular papillary projections may have eroded, causing the urine to be bloodstained or contain large clots of blood. In the cystitis associated with Sudan grass, soft masses of calcium carbonate may accumulate in the bladder and the vaginal wall may be inflamed and coated with the same material.
Antimicrobial agents are indicated to control the infection and determination of the antimicrobial susceptibility of the causative bacteria is essential. Relapses are common unless treatment is continued for a minimum of 7 and preferably 14 days. Repeated bacterial culture of urine at least once during and again within 7–10 days after completion of treatment should be used to assess the success of therapy. Recurrence of the infection is usually due to failure to eliminate foci of infection in the accessory glands and in the bladder wall.
The clinical and laboratory findings of cystitis resemble those of pyelonephritis and cystic urolithiasis.
• Pyelonephritis is commonly accompanied by bladder involvement and differentiation depends on whether there are lesions in the kidney. This may be determined by rectal examination but in many cases it is not possible to make a firm decision. Provided the causative bacteria can be identified this is probably not of major importance as the treatment will be the same in either case. However, the prognosis in pyelonephritis is less favorable than in cystitis. Thickening of the bladder wall, which may suggest a diagnosis of cystitis, occurs also in enzootic hematuria and in poisoning by the yellow-wood tree (Terminalia oblongata) in cattle and by sorghum in horses
• The presence of calculi in the bladder can usually be detected by rectal examination, by ultrasonographic examination, by endoscopic examination in female ruminants and in both sexes of horses, or by radiographic examination in smaller animals
• Urethral obstruction may also cause frequent attempts at urination but the urine flow is greatly restricted, usually only drops are voided and the distended bladder can be felt on rectal examination
The prognosis in chronic cases is poor because of the difficulty of completely eradicating the infection and the common secondary involvement of the kidney. Free access to water should be permitted at all times to insure a free flow of urine.
Paralysis of the bladder is uncommon in large animals. Paralysis usually occurs as a result of neurological diseases affecting the lumbosacral spinal cord such as equine herpes myelopathy and cauda equina syndrome, and particularly ascending spinal meningitis in lambs after tail docking. In all species, compression of the lumbar spinal cord by neoplasia (lymphosarcoma, melanoma) or infected tissue (vertebral osteomyelitis) can cause paralysis of the bladder. Excessive tension on the tail, such as with tail ropes or use of the tail for restraint in cattle, can injure the cauda equina and cause bladder paralysis. In horses, spinal cord degeneration following consumption of sorghum can lead to bladder paralysis and posterior ataxia. Iatrogenic bladder paralysis occurs in horses in which there has been epidural injection of an excessive quantity of alcohol. Equine protozoal myeloencephalitis can cause signs of cauda equina dysfunction in horses, as does equine polyneuritis. In some horses, idiopathic bladder paralysis and overflow incontinence may occur sporadically in the absence of other neurological or systemic signs.2 When the bladder is markedly distended from a urinary tract obstruction, it may take several days after removal of the obstruction before normal bladder tone returns.
When bladder paralysis arises from spinal cord disease, other upper or lower motor neuron signs are usually present. Bladder involvement is indicated by incontinence with constant or intermittent dribbling of urine. Urine flow is often increased during exercise. The bladder is enlarged on examination per rectum and urine can be easily expressed by manual compression. In horses, chronic distension of the bladder leads to accumulation of a sludge of calcium carbonate crystals. Urine stasis produces ideal conditions for bacterial growth and cystitis is a common sequel. Treatment is supportive and aimed at relieving bladder distension by regular catheterization and lavage. During catheterization, care must be taken to avoid introducing infection. Manual or pharmacologically induced emptying of the bladder is incomplete so there is a constant risk of cystitis. Pharmacological enhancement of bladder emptying can sometimes be achieved by administration of parasympathomimetic agents such as bethanechol (parasympathetic stimulation via the pelvic nerve stimulates detrusor contraction) and sympatholytics such as prazosin and phenoxybenzamine (sympathetic stimulation via the hypogastric nerve causes detrusor relaxation and internal sphincter contraction). The administration of antimicrobial agents as a prophylaxis against the development of cystitis is advisable. The prognosis for paralysis associated with spinal cord disease depends on the prognosis for the primary disease. Paralysis in the absence of spinal cord disease has a poor prognosis.
Cattle ingesting Cistus salvifolius, a shrub found in the Mediterranean region, had urinary retention as the primary clinical sign.3 Cattle had decreased appetites and rumen motility, weight loss, and persistent elevation of the tail head and difficulty in urination. A greatly distended urinary bladder was always detected on palpation per rectum. The mortality rate in advanced cases was high, and affected animals have severe cystitis, pyelonephritis and a marked increase in bladder wall thickness. No evidence of neurological injury was present, and it is likely that urine retention was secondary to severe cystitis and swelling of the bladder wall that prevented normal urination.
This occurs most commonly in castrated male ruminants as a sequel to obstruction of the urethra by calculi. Rare cases are recorded in cows as a sequel to a difficult parturition1-3 and in mares after normal parturition,4 possibly because of compression of a full bladder during foaling. In cattle, abnormal fetal position during prolonged dystocia is suspected to obstruct the urethra and distend the bladder. Subsequent manipulation within the pelvic canal during correction of the dystocia is suspected to lead to rupture of a distended bladder.3 Uroperitoneum in foals is discussed in the next section.
After the bladder ruptures, uroperitoneum results in a series of abnormalities that arise from failure of the excretory process combined with solute and fluid redistribution between the peritoneal fluid and extracellular fluid. The peritoneal membrane serves as a semipermeable membrane through which low-molecular-weight solutes readily pass. High-molecular-weight compounds also diffuse across the peritoneal membrane but at a much slower rate. Urine is usually hypertonic especially in animals whose water intake is decreased by uremia. Osmotic pressure from hypertonic urine promotes movement of extracellular water into the peritoneal cavity. This movement, combined with reduced intake, results in clinical dehydration. Urine usually has a lower concentration of sodium and chloride and higher concentrations of urea, creatinine, potassium, and phosphate than plasma. Diffusion along these concentration gradients across the peritoneal membrane results in a general pattern of azotemia with hyponatremia, hypochloremia, hyperkalemia, and hyperphosphatemia.5 There are minor differences between species in these general biochemical changes. In particular, the blood concentration of urea rises much more slowly in ruminants than in horses, and hyperkalemia is not as common in ruminants as in horses because excessive potassium can be excreted in the saliva and therefore eliminated in the feces.
Bladder rupture leads to gradual development of ascites from uroperitoneum, ruminal stasis, constipation, and depression. In cattle, uremia may take 1–2 weeks to develop to the point where euthanasia is necessary. The degree of uremia between individual patients can be highly variable. With therapy, the survival rate of steers in one study was 49%. The best predictor of survival among clinical pathology tests was the serum phosphate concentration: all animals with levels greater than 9.0 mg/dL (2.9 mmol/L) died.6 In mature horses, clinical signs of depression, anorexia, colic, abdominal distension, and uremia develop within 1–2 days following rupture.
In cases of ascites or when urinary tract obstruction is evident, it is important in considering treatment and prognosis to determine whether the bladder has ruptured. The urea and creatinine concentrations in plasma can be compared to the values in the peritoneal fluid. The ratio of urea in peritoneal fluid to that in serum is a good guide in the early stages, but after 40 hours the ratio of the peritoneal to serum creatinine greater than 2:1 is diagnostic of uroperitoneum.7 Treatment is surgical with a goal of bladder repair. To avoid the costs of laparotomy in feedlot animals, a urethrostomy is created or an indwelling catheter is placed and the rupture is allowed to repair itself.
Uroperitoneum, the accumulation of urine in the peritoneal cavity, occurs in foals as a result of a variety of situations:
• Congenital (i.e. present at birth) rupture of the bladder
• Bladder rupture associated with sepsis
• Rupture of the urachus, often secondary to sepsis
• Avulsion of the bladder from its urachal attachment, presumably as a result of trauma or strenuous exercise1
• Rarely, as embryological failure of the halves of the bladder to unite (schistocystitis)1
The etiology of congenital rupture is unclear, but its association with birth, markedly greater prevalence in colts, and the traumatic nature of the lesion suggests that it occurs during birth as a result of compression of a distended bladder. Intra-abdominal pressures of the mare during parturition are large, and these compressive forces are experienced by the foal during phase 2 of parturition. Compression of a distended bladder can cause rupture. The greater prevalence in colts is speculated to be a result of the greater resistance to bladder emptying conferred by the longer urethra of male foals.
Rupture of the bladder occurs as a distinct entity in septic foals. The underlying reason for bladder rupture is unclear but is usually related to infection, inflammation and necrosis of the lower urinary tract.2,3 This cause of uroperitoneum in foals is increasingly recognized as the most common, especially amongst hospitalized foals.
Rupture of the urachus occurs in septic foals. It is probably of similar etiology to rupture of the bladder in septic foals. The urachus of affected foals almost always has infection, inflammation and necrosis evident on histological examination.
Avulsion of the bladder from its urachal attachments is presumed to occur as a result of trauma, such as might occur with vigorous exercise. The possibility also exists that there is an underlying defect in affected foals, such as urachitis or omphalitis.
Embryological failure of the halves of the bladder to unite during organogenesis has been reported anecdotally and in case reports, although adequate documentation of its occurrence is lacking.1,2 This defect would be a true congenital anomaly, arising during gestation.
Ureteral defects are an uncommon cause of uroperitoneum in foals. The defects appear to be congenital and more common in fillies. Both ureters can be affected.4
The relative frequency of these diseases is that approximately 20% of foals with uroperitoneum do so because of urachal rupture, approximately 30% because of rupture of the dorsal bladder wall, 18% because of rupture of the ventral bladder wall and the remainder because of multiple defects involving combinations of the urachus, dorsal and ventral bladder.3,5
Uroperitoneum also occurs in calves as a consequence of umbilical infection.6
The epidemiology of uroperitoneum is not well documented. The incidence in foals appears to be approximately 0.2%, although this estimate is based on a study conducted 50 years ago.7 The prevalence in hospitalized foals is 2.5%.3 Male foals are at greater risk than are females for congenital rupture, more than 80% of foals with this disease being colts.5,8 In contrast, there is no sex predilection for development of uroperitoneum in foals with sepsis.2,3 The age at diagnosis ranges from 2 to more than 60 days, with most cases recognized within the first 2 weeks of life. The average age at diagnosis is approximately 4–5 days, although the age at presentation depends on the underlying cause. Foals with congenital rupture of the bladder or ureteral defects are usually recognized at about 3–5 days of age, while foals with uroperitoneum secondary to sepsis are usually older (5–9 days of age, but up to 60 days).2,3,5 The prognosis for survival for foals with uroperitoneum depends on the underlying cause and availability of appropriate treatment. Foals with congenital rupture of the bladder that are recognized and treated in a timely fashion have an excellent prognosis (> 80%) for survival, whereas those with uroperitoneum secondary to sepsis have a more guarded prognosis (50–60%) because of the sepsis.2,3,5
The pathophysiology of uroperitoneum is that of postrenal azotemia. Regardless of the underlying cause of the uroperitoneum, accumulation of urine within the peritoneal cavity results in substantial electrolyte, acid–base and cardiovascular effects in affected foals. The basic principle is that affected foals are unable to excrete metabolic waste products that are normally excreted in the urine, and are unable to maintain water and electrolyte balance. Young foals derive almost all of their nutritional needs, including water, from mare’s milk. Mare’s milk has a low sodium concentration (approximately 12 mEq/L) and a high potassium concentration (25 mEq/L) compared to serum, and a dry matter content of 11%.9 Therefore, foals ingest a diet that contains a large quantity of water and potassium but little sodium. Consequently, the urine of foals contains little sodium (7 mmol/L) and has a low osmolality (100 mosmol/kg).10,11 Leakage of urine into the peritoneum, a semipermeable membrane, results in considerable fluid and electrolyte shifts. Partial equilibration of water and electrolytes across the peritoneal membrane results from diffusion of water from the peritoneum with resultant dilution of serum and reductions in serum sodium and chloride concentrations. The low concentration of sodium in uriniferous peritoneal fluid favors diffusion of sodium from the blood into the peritoneal fluid, with the result that there is a reduction in intravascular sodium content and a consequent reduction in effective circulating volume. Excretion of relatively large quantities of potassium in urine and accumulation of potassium-rich fluid in the peritoneum allows diffusion of potassium into the blood and an increase in plasma potassium concentration.
The peritoneal membrane is permeable to creatinine and urea, as evidenced by the efficacy of peritoneal lavage in treatment of renal failure in a variety of species, including horses. Consequently, serum creatinine and urea concentrations are higher in foals with uroperitoneum than in unaffected foals. However, equilibration of concentrations of these compounds is not complete and peritoneal fluid concentrations of urea, creatinine, and potassium are higher than those in serum.
Foals with uroperitoneum have compromised circulatory function because of reduced effective circulating plasma (blood) volume, despite having an increased total body water content. Circulatory function is further impaired by a combination of the hyperkalemia, abdominal distension and accumulation of fluid in the pleural space, with the result that foals with uroperitoneum can have signs of mild to moderate circulatory compromise.
Hyperkalemia and acidosis associated with uroperitoneum predispose affected foals to development of malignant cardiac rhythm, including ventricular tachycardia and fibrillation. This abnormal cardiac rhythm is a common cause of death of affected foals.
Clinical signs in foals with uroperitoneum depend in part on the underlying disease. Foals with congenital rupture or mild sepsis have progressive signs of lethargy, decreased appetite, mild abdominal discomfort, and abdominal distension. These signs usually first become apparent at 2–4 days of age. These foals do not typically have a fever. As the disease progresses and the amount of urine accumulated in the peritoneum increases, foals have progressive distension of the abdomen and make frequent attempts to urinate. Foals attempting to urinate ventroflex the back (mild lordosis) and have a wide-based stance, in contrast with foals with tenesmus, which characteristically have a narrow-based stance (all four limbs being under the body) and arch their back. Affected foals sometimes produce small quantities of urine, but usually there is lack of urination. Abdominal distension is most apparent when the foal is standing. In moderate to severe cases there is a readily appreciable fluid wave on ballotment of the abdomen. As abdominal distension increases the foal’s tidal volume is impaired and breathing becomes rapid and shallow. The extremities become cool as cardiovascular function is impaired.
Ventral edema and preputial swelling occur in some foals. Foals with a urachal rupture close to or within the abdominal wall or in the subcutaneous tissues will have subcutaneous accumulation of urine (which can be mistaken for ventral edema).
Foals with uroperitoneum secondary to sepsis usually have signs of sepsis as the initial and predominant sign of disease. These signs can range from mild fever and enlargement of the umbilical structures to septic shock and its attendant abnormalities. Initial signs of uroperitoneum in these foals are easily overlooked. As the disease develops these foals have progressive abdominal distension. Signs of cardiovascular dysfunction can be incorrectly attributed to worsening of sepsis. It is important when treating septic foals to maintain a high index of suspicion and constant vigilance for development of uroperitoneum.
Infusion of contrast agents, such as methylene blue or fluorescein, into the bladder with subsequent detection of these compounds in the peritoneal fluid has been used to diagnose uroperitoneum. However, use of this method of diagnosis is now obsolete except in those instances in which ultrasonographic examination of the foal is not possible.
Ultrasonographic examination of the abdomen of foals has simplified detection of uroperitoneum in foals and is the preferred imaging modality for detection of excessive peritoneal fluid in foals. The ultrasound examination is best performed with a 5 MHz sector scanner, with more detailed examination of the umbilical structures performed using a 7 MHz linear or sector scanner. However, diagnosis of the presence of excessive peritoneal fluid can be achieved using a 7 MHz linear scanner, such as is routinely used for examination of the mare reproductive tract. The examination is performed transcutaneously.
Ultrasonography reveals the presence of an excessive quantity of fluid that is minimally echogenic. Intestine, mesentery, and omentum are readily visualized floating in this fluid. The presence of a large quantity of minimally echogenic fluid in the peritoneum of foals is very specific (effectively 100%) for uroperitoneum. The procedure is also sensitive, especially if performed repeatedly to detect changes in the amount of fluid, especially when the initial examination is equivocal. The umbilical structures should be examined closely and the urachus tracked to the bladder. Frequently a defect in the urachus or umbilicus is identified.3 The thorax of affected foals should also be examined, as foals with large quantities of urine in the peritoneum often have a substantial accumulation of pleural fluid. This can be important when considering anesthesia in these foals.
Radiographic examination of foals with suspected uroperitoneum is rarely performed because of the utility of ultrasonographic examination in this disease. Plain abdominal radiography is of limited usefulness in the detection of uroperitoneum or localizing the source of urine. Positive contrast cystography using a 10% solution of iohexol or similar water-soluble contrast agent administered into the bladder through a Foley catheter can be useful in detection of leaks, especially small leaks that cannot be visualized on ultrasonographic examination. Care should be taken to insure that the bladder is sufficiently distended to insure that any leak is visualized. Use of barium contrast medium or negative-contrast cystography (infusion of air into the bladder) are contraindicated. Intravenous pyelography is of very limited usefulness in the detection of ureteral defects because of the difficulty in localizing the site of the leak.
Electrocardiographic examination can reveal cardiac arrest, atrioventricular block, presumed intraventricular block, ventricular premature complexes, ventricular tachycardia and ventricular fibrillation.5,8 These abnormalities are most likely to occur in foals that are hyperkalemic at the time of induction of anesthesia.
Foals with uncomplicated uroperitoneum have hyponatremia, hypochloremia, hypobicarbonatemia (metabolic acidosis), acidemia, hyperkalemia, and azotemia. Severely affected foals can be profoundly hyponatremic (<110 mEq/L) and hyperkalemic (>7 mEq/L).2,5 Serum creatinine and urea nitrogen concentrations are elevated. When interpreting serum urea nitrogen concentrations in foals it should be borne in mind that the urea concentration in normal foals is much lower than in adults (see Table 3.6).
Diagnosis based on serum electrolyte abnormalities is confounded in hospitalized foals that are being treated with intravenous fluids.2,3 Administration of fluids prevents the development of hyponatremia and hypochloremia in septic foals that develop uroperitoneum during the course of their disease. However, fluid administration does not prevent the increases in serum creatinine or urea nitrogen concentration.2
Hematological abnormalities reflect any underlying sepsis.
Analysis of peritoneal fluid reveals that it has a low specific gravity (< 1.010), low total protein concentration (<< 2.5 g/dL, 25 g/L) and low white cell count (<1000 cells/μL, 1 × 109 cells/L). It can have a uriniferous odor, but this is not a reliable diagnostic sign. Peritoneal fluid from foals with uroperitoneum has elevated concentrations of creatinine (usually twice that in a contemporaneous serum sample), urea nitrogen (twice that of serum) and potassium.5 Microscopic examination of the fluid can reveal calcium carbonate crystals, the presence of which is diagnostic for urine.
Necropsy examination confirms the presence of uroperitoneum and the structural defect allowing leakage of urine into the abdomen. The defect can have signs of healing, which can make it readily confused with a malformation, because affected foals can survive for days after the rupture occurs – sufficient time for partial healing of the defect.
Demonstration of an excessive quantity of poorly echogenic fluid in the abdomen of a foal that is passing little if any urine and that has hyponatremia and hyperkalemia is diagnostic of uroabdomen. Confirmation of the diagnosis can be achieved by measurement of creatinine concentration in the peritoneal fluid. Ultrasonographic examination greatly facilitates the diagnosis.
The principal differential diagnoses for azotemia in foals are uroperitoneum and renal disease. Primary renal disease in foals can cause hyponatremia, hyperkalemia, and azotemia, but there is no accumulation of fluid in the peritoneum. Additionally, in primary renal disease there are abnormalities in urine composition (presence of blood, protein, leukocytes, and casts). Hyponatremia and hyperkalemia can occur in foals with enterocolitis, but the other clinical signs are diagnostic of this disease. Addison’s disease (mineralocorticoid deficiency) does occur in foals but is rare, and there is no accumulation of fluid in the abdomen.12
Definitive treatment of uroperitoneum in foals is surgical repair of the defect. However, there is no need for surgery on an emergency basis. Rather, care should be taken to correct life-threatening electrolyte and fluid abnormalities before the foal is subjected to anesthesia. Principles of medical treatment are prevention of potentially lethal cardiac arrhythmia, correction of electrolyte, fluid and acid– base abnormalities and relief of abdominal distension.
Potentially life-threatening electrolyte abnormalities, especially hyperkalemia, should be corrected urgently and before any attempted surgical correction of the anatomical defect.
Correction of fluid and electrolyte abnormalities is best achieved by draining the abdomen and insuring continued voiding of urine while administering isotonic fluids intravenously. Because the foal has normal kidney function, draining urine from the abdomen allows the foal to restore normal serum electrolyte concentrations and fluid balance provided that the foal is allowed to nurse and/or is administered parenteral fluids.
Peritoneal drainage is achieved by placement of a catheter into the abdomen. The catheter should be placed with a view to it remaining in place until the electrolyte abnormalities have been corrected and the foal is a suitable candidate for surgical repair of the anatomical defect. An ideal catheter is a Foley balloon-tipped catheter placed into the abdomen through a small (5 mm) incision in the skin and external abdominal wall. The catheter should be placed in the inguinal region and to one side of the linear alba, so as to avoid injury and contamination of a future surgical site and to minimize the chances of the catheter being plugged by omentum. The catheter is inserted under local anesthesia and the balloon is inflated to secure the catheter in the abdomen. The catheter can be further secured by a suture. Sedation or tranquilization should be avoided in foals at risk of cardiac or respiratory distress because of the electrolyte abnormalities. Urine should be allowed to drain from the catheter into a closed collection system that minimizes the chances of ascending infection of the peritoneum.
Hyperkalemia is usually readily corrected by peritoneal drainage and administration of potassium-free fluid, such as 0.9% sodium chloride. Serum potassium concentration declines quickly when effective peritoneal drainage is obtained and serum potassium concentrations can normalize in 8–12 hours. If emergency management of hyperkalemia is required administration of 5% dextrose either alone or, if hyponatremia is also present, in 0.9% sodium chloride, is effective in reducing serum potassium concentration. Sodium bicarbonate (1–3 mEq/kg BW, intravenously) will also decrease serum potassium concentration. Calcium gluconate antagonizes the effect of hyperkalemia on cardiac function and is useful in the treatment of hyperkalemic arrhythmias. The serum potassium concentration should be less than 5.5 mEq/L before the foal is anesthetized. Mare’s milk, which is rich in potassium, should be withheld until the serum potassium concentration is below the required level.
Hyponatremia is resolved by drainage of the peritoneum and administration of 0.9–1.8% sodium chloride intravenously. Serum sodium concentration, especially if markedly low, should be corrected slowly to prevent the development of hyponatremic encephalopathy. Serum sodium concentrations should be increased by approximately 1 (mEq/L)/h.
Affected foals should be administered broad-spectrum antibiotics because of the risk of peritonitis and because many foals with uroperitoneum have sepsis. The immune status of young foals should be examined by measurement of serum IgG concentration and, if it is less than 800 mg/dL (8 g/L), the foal should receive 20–40 mL/kg of plasma.
Correction of the defect in the bladder or urachus is surgical. Nonsurgical management has been described in a foal in which a Foley catheter was inserted in the bladder and left in place for 5 days. The bladder was constantly drained of urine and this allowed the tear to heal.13 This technique offers an alternative to surgical repair of bladder rupture. However, surgical repair is definitive and is the recommended method of treatment.
Subcutaneous rupture of the urachus can similarly be treated by placement of a Foley catheter through the patent urachus and into the bladder. The defect in the urachus is then allowed to heal and the catheter is removed in 3–6 days.
1 Hardy J. Equine Vet Educ. 1998;10:21.
2 Dunkel B, et al. J Vet Intern Med. 2005;19:889.
3 Kablack KA, et al. Equine Vet J. 2000;32:505.
4 Divers TJ, et al. J Am Vet Med Assoc. 1988;192:384.
5 Richardson DW, Kohn CW. J Am Vet Med Assoc. 1983;182:267.
6 Bell GJ, et al. Vet Rec. 2004;154:508.
7 Bain AM. Aust Vet J. 1954;30:9.
8 Hackett RP. Compend Contin Educ Pract Vet. 1984;6:S488.
9 Ullrey DE, et al. J Anim Sci. 1966;25:217.
10 Pipkin FB, et al. J Reprod Fertil Suppl. 1991;44:736.
11 Brewer BD, et al. J Vet Intern Med. 1991;5:28.
12 Couetill LL, Hoffman AM. J Am Vet Med Assoc. 1998;212:1594.
13 Lavoie JP, Harnagel SH. J Am Vet Med Assoc. 1988;192:1577.
Urolithiasis is common as a subclinical disorder among ruminants raised in management systems where the ration is composed primarily of grain or where animals graze certain types of pasture. In these situations, 40–60% of animals may form calculi in their urinary tract. Urolithiasis becomes an important clinical disease of castrated male ruminants when calculi cause urinary tract obstruction, usually obstruction of the urethra. Urethral obstruction is characterized clinically by complete retention of urine, frequent unsuccessful attempts to urinate and distension of the bladder. Urethral perforation and rupture of the bladder can be sequelae. Mortality is high in cases of urethral obstruction and treatment is surgical. As a result, prevention is important to limit losses from urolithiasis.
Urinary calculi, or uroliths, form when inorganic and organic urinary solutes are precipitated out of solution. The precipitates occur as crystals or as amorphous ‘deposits’. Calculi form over a long period by a gradual accumulation of precipitate around a nidus. An organic matrix is an integral part of most types of calculus. Several factors affect the rate of urolith formation, including conditions that affect the concentration of specific solutes in urine, the ease with which solutes are precipitated out of solution, the provision of a nidus and the tendency to concretion of precipitates. These are presented under Epidemiology. Factors that contribute to the clinical syndrome of obstructive urolithiasis are dealt with separately.
Urolithiasis occurs in all ruminant species but is of greatest economic importance in feeder steers and wethers (castrated lambs) being fed heavy concentrate rations, and animals on range pasture in particular problem areas. These range areas are associated with the presence of pasture plants containing large quantities of oxalate, estrogens, or silica. When cattle graze pasture containing plants with high levels of silica, uroliths occur in animals of all ages and sexes.1 The prevalence of uroliths is about the same in cows, heifers, bulls, and steers grazing on the same pasture and they may even occur in newborn calves. Females and bulls usually pass the calculi and obstructive urolithiasis is primarily a problem in castrated male animals.
Obstructive urolithiasis is the most common urinary tract disease in breeding rams and goats.2
There are three main groups of factors that contribute to urolithiasis:
A nidus favors the deposition of crystals about itself. A nidus may be a group of desquamated epithelial cells or necrotic tissue that may be formed as a result in occasional cases from local infection in the urinary tract. When large numbers of animals are affected it is probable that some other factor, such as a deficiency of vitamin A or the administration of estrogens, is the cause of excessive epithelial desquamation. When stilbestrol was used as a growth promoter, mortality rates of 20% due to obstructive urolithiasis were recorded in wethers receiving stilbestrol implants compared with no mortalities in a control group. Diets low in vitamin A have been suspected as a cause of urolithiasis but vitamin A deficiency does not appear to be a major causative factor.
Urine is a highly saturated solution containing a large number of solutes, many of them in higher concentrations than their individual solubilities permit in a simple solution. Several factors may explain why solutes remain in solution. Probably the most important factor in preventing precipitation is the presence of protective colloids that convert urine into a gel. These colloids are efficient up to a point, but their capacity to maintain the solution may be overcome by abnormalities in one or more of a number of other factors. Even in normal animals, crystals of a number of solutes may be present in the urine intermittently and urine must be considered to be an unstable solution. The physical characteristics of urine, the amount of solute presented to the kidney for excretion and the balance between water and solute in urine all influence the ease of calculus formation. In most cases these factors can also be influenced by management practices.
The pH of urine affects the solubility of some solutes, mixed phosphate and carbonate calculi being more readily formed in an alkaline than an acid medium.
Ammonium chloride or phosphoric acid added to the rations of steers increases the acidity of the urine and reduces the incidence of calculi. The mechanism is uncertain but is probably related to the effect of pH on the stability of the urinary colloids or the effect of diuresis. In contrast, variations in pH between 1 and 8 have little influence on the solubility of silicic acid, the form of silica excreted in the urine of ruminants. As a result, dietary supplementation with ammonium chloride does not consistently prevent the formation of siliceous calculi.3The amount of solute presented to the kidney for excretion is influenced by the diet. Some pasture plants can contain up to 6% silica. Although ruminants grazing on these plants absorb only a small portion of the ingested silica, the kidney is the major route of excretion of absorbed silicic acid. The urine of these animals often becomes supersaturated with silicic acid, which promotes the polymerization or precipitation of the silicic acid and calculus formation.
Feeding sodium chloride prevents the formation of silica calculi by reducing the concentration of silicic acid in the urine and maintaining it below the saturation concentration. An excessive intake of minerals may occur from highly mineralized artesian water, or from diets containing high concentrations, particularly of phosphates in heavy-concentrate diets. Sheep with a high dietary intake of phosphorus have an increased concentration of phosphorus in their urine and an increased development of calculi. In cattle, sediment begins to appear in urine when concentrates reach 1.5% of the body weight, and urolithiasis formation begins when concentrates have been fed for 2 months at the rate of 2.5% of the animal’s body weight.
Diets high in magnesium such as some calf milk replacers have also been associated with an increasing incidence of obstructive urolithiasis.4 Supplemental calcium in the diet helps prevent calculus formation when phosphate or magnesium4 intake is high.
Ingestion of plants with a high oxalic acid content can be a risk factor for formation of calcium carbonate calculi in sheep. Although dietary excesses contribute to certain types of urolithiasis, calculus formation can rarely be recreated experimentally by simple overfeeding. The process of formation of urinary calculi is more complex than a simple dietary excess. However, recognition of associations between diet and some types of urolithiasis has been useful in developing preventive strategies.
Feeding practices can influence the function of the kidney and may contribute to calculus formation. In sheep fed grain in a few large meals, there is a marked reduction in urine volume and a marked increase in urine concentration and calcium excretion at the time of feeding. These short-term changes in urine composition may be factors in the development of uroliths.
The concentration of urine is an important determinant of the concentration of individual solutes in the urine. Although it is difficult to induce urolithiasis by restricting access to water, concentrated urine is a risk factor for calculus formation. Animals can be forced to produce concentrated urine because of lack of easy access to water, a particular problem in pastured animals, lack of familiarity with water delivery systems and poor quality of available water. Water deprivation can be exacerbated by heavy fluid loss by sweating in hot, arid climates.
Most calculi, and siliceous calculi in particular, are composed of organic matter as well as minerals. This organic component is mucoprotein, particularly its mucopolysaccharide fraction. It acts as a cementing agent and favors the formation of calculi when precipitates are present. The mucoprotein content of urine of feeder steers and lambs is increased by heavy concentrate–low roughage rations, by the feeding of pelleted rations, even more so by implantation with diethylstilbestrol and, combined with a high dietary intake of phosphate, may be an important cause of urolithiasis in this class of livestock. These high levels of mucoprotein in urine may be the result of a rapid turnover of supporting tissues in animals that are making rapid gains in weight.
Stasis of urine favors precipitation of solutes, probably by virtue of the infection that commonly follows, providing cellular material for a nidus. Certain feeds, including cottonseed meal and milo sorghum, are credited with causing more urolithiasis than other feeds. Alfalfa is in an indeterminate position: by some observers it is thought to cause the formation of calculi, by others to be a valuable aid in preventing their formation. Pelleting appears to increase calculi formation if the ration already has this tendency.
Attempts to produce urolithiasis experimentally by varying any of the above factors are usually unsuccessful and natural cases most probably occur as a result of the interaction of several factors. In feedlots a combination of high mineral feeding and a high level of mucoprotein in the urine associated with rapid growth are probably the important factors in most instances. In range animals a high intake of mineralized water, or oxalate or silica in plants, are most commonly associated with a high incidence of urinary calculi, but again other predisposing factors, including deprivation or excessive loss of water, may contribute to the development of the disease. Limited water intake at weaning and in very cold weather may also be a contributory factor.
The chemical composition of urethral calculi varies and appears to depend largely on the dietary intake of individual elements. In semi-arid areas such as the great plains of North America1 and parts of Australia, the dominant pasture grasses have a high content of silica. Cattle and sheep grazing these pastures have a high prevalence of siliceous calculi. Calculi containing calcium carbonate are more common in animals on clover-rich pasture, or when oxalate-containing plants abound. Calcium, ammonium, and magnesium carbonate are also common constituents of calculi in cattle and sheep at pasture.
Sheep and steers in feedlots usually have calculi composed of struvite, magnesium ammonium phosphate. High concentrations of magnesium in feedlot rations also cause a high prevalence of magnesium ammonium phosphate calculi in lambs.5 Experimental feeding of a ration with a high magnesium content increases the prevalence of calcium apatite urolithiasis in calves and can be prevented by supplementary feeding with calcium.4 Oxalate calculi are extremely rare in ruminants but have been observed in goats and induced experimentally in feedlot cattle. Xanthine calculi in sheep are recorded in some areas in New Zealand where pasture is poor.
Estrogenic subterranean clover can cause urinary tract obstruction in wethers in a number of ways. Soft, moist, yellow calculi containing 2-benzocoumarins, isoflavones and indigotin–indirubin have been observed. Calculi or unformed sediments of benzocoumarins (urolithins) and 4′-O-methylequol, either singly or in various combinations with equol, formonentin, biochanin A, indigotin and indirubin, also occur. Obstruction is promoted by estrogenic stimulation of squamous metaplasia of the urethral epithelium, accessory sex glandular enlargement and mucus secretion. Pastures containing these plants are also reputed to cause urinary obstruction by calculi consisting of calcium carbonate. Feedlot lambs receiving a supplement of stilbestrol (1 mg/kg of feed or 2 mg per lamb daily) developed urethral obstruction believed to be caused primarily by plugs of mucoprotein. The accessory sex glands were also enlarged.
The risk factors important in the formation of urinary calculi are also important in the development of obstructive urolithiasis.
The size of individual calculi and the amount of calculus material are both important in the development of urethral obstruction. Often the obstruction is caused by one stone, although an aggregation of many small struvite calculi often causes obstruction in sheep fed high-concentrate rations.
Once calculi form, the most important factor contributing to the occurrence of obstruction is the diameter of the urethra. Wethers (castrated lambs) and steers (castrated cattle) are most commonly affected because of the relatively small diameter of the urethra in these animals. Castration has a significant impact on the diameter of the urethra in steers. When the urethral diameter of late castrates (6 months old) was compared to early castrates (2 months), it was found to be 8% larger and would be able to expel a calculus that was 13% larger than a calculus passed by early castrates.6 Bulls can usually pass calculi that are 44% larger than those that could be passed by an early castrated steer.
Urethral obstruction may occur at any site but is most common at the sigmoid flexure in steers and in the vermiform appendage or at the sigmoid flexure in wethers or rams, all sites where the urethra narrows. Urolithiasis is as common in females as in males, but obstruction rarely if ever occurs because of the shortness and large diameter of the urethra. Repeated attacks of obstructive urolithiasis are not uncommon in wethers and steers and at necropsy up to 200 calculi may be found in various parts of the tract of one animal. However, generally, a single calculus causes obstruction in cattle whereas multiple calculi are common in sheep.
In North America obstructive urolithiasis due to siliceous calculi is most common in beef feeder cattle during the fall and winter months. The calves are weaned at 6–8 months and moved from pasture to a feedlot where they are fed roughage and grain. The incidence of obstructive urolithiasis is highest during the early part of the feeding period and during cold weather, when the consumption of water may be decreased.
Although the occurrence of obstructive urolithiasis is usually sporadic, with cases occurring at irregular intervals in a group of animals, outbreaks may occur affecting a large number of animals in a short time. In outbreaks it is probable that factors are present that favor the development of calculi, as well as the development of obstruction. For example, multiple cases of obstructive urolithiasis can occur in lambs within a few weeks of introducing a concentrated ration. Obstructive urolithiasis increases in occurrence with age but has occurred in lambs as young as 1 month of age.
Urinary calculi are commonly observed at necropsy in normal animals, and in many appear to cause little or no harm. Calculi may be present in kidneys, ureters, bladder, and urethra. In a few animals pyelonephritis, cystitis, and urethral obstruction may occur. Obstruction of one ureter may cause unilateral hydronephrosis, with compensation by the contralateral kidney. The major clinical manifestation of urolithiasis is urethral obstruction, particularly in wethers and steers. This difference between urolithiasis and obstructive urolithiasis is an important one. Simple urolithiasis has relatively little importance but obstructive urolithiasis is a fatal disease unless the obstruction is relieved. Rupture of the urethra or bladder occurs within 2–3 days if the obstruction is not relieved and the animal dies of uremia or secondary bacterial infection. Rupture of the bladder is more likely to occur with a spherical, smooth calculus that causes complete obstruction of the urethra. Rupture of the urethra is more common with irregularly shaped stones that cause partial obstruction and pressure necrosis of the urethral wall.
Calculi in the renal pelvis or ureters are not usually diagnosed antemortem although obstruction of a ureter may be detectable on rectal examination, especially if it is accompanied by hydronephrosis. Occasionally the exit from the renal pelvis is blocked and the acute distension that results may cause acute pain, accompanied by stiffness of the gait and pain on pressure over the loins. Calculi in the bladder may cause cystitis and are manifested by signs of that disease.
This is a common occurrence in steers and wethers and causes a characteristic syndrome of abdominal pain with kicking at the belly, treading with the hind feet and swishing of the tail. Repeated twitching of the penis, sufficient to shake the prepuce, is often observed, and the animal may make strenuous efforts to urinate, accompanied by straining, grunting and grating of the teeth, but these result in the passage of only a few drops of bloodstained urine. A heavy precipitate of crystals is often visible on the preputial hairs or on the inside of the thighs. Some animals with urethral obstruction will have a dry prepuce because of the absence of urination, although this sign is not specific for urolithiasis.
The passage of a flexible catheter up the urethra, after relaxing the penis by lumbosacral epidural anesthesia, by pudendal nerve block or by administering an ataractic drug, may make it possible to locate the site of obstructions that are anterior to the sigmoid flexure. However, catheterization of the urethra from the glans penis to the bladder is almost impossible in cattle and ruminants because of the urethral diverticulum with its valve.7 A precurved coronary catheter has been used to catheterize the bladder of calves and goats8 but requires fluoroscopic guidance.
Cattle with incomplete obstruction – ‘dribblers’ – will pass small amounts of bloodstained urine frequently. Occasionally a small stream of urine will be voided followed by a complete blockage. This confuses the diagnosis. In these the calculus is triangular in shape and allows small amounts of urine to move past the obstruction at irregular intervals. However, these are rare.
The entire length of the penis must be palpated for evidence of a painful swelling from the preputial orifice to the scrotum, above the scrotum to locate the sigmoid flexure and proximally up the perineum as far as possible.
In rams, bucks, and wethers the urethral process of the exteriorized penis must be examined for enlargement and the presence of multiple calculi. Extrusion of the penis is difficult in prepubertal sheep and goats because of the presence of an attachment from the prepuce to the glans penis; loss of this attachment is mediated by testosterone and is usually complete by the onset of puberty,9 although separation may not occur in castrated animals.10 Penile extrusion is facilitated by xylazine sedation and positioning the animals with lumbosacral flexion. Abnormal urethral processes should be amputated and in many animals grit is detected during urethral transection.
On rectal examination, when the size of the animal is appropriate, the urethra and bladder are palpably distended and the urethra is painful and pulsates on manipulation.
In rams with obstructive urolithiasis, sudden depression, inappetence, stamping the feet, tail swishing, kicking at the abdomen, bruxism, anuria or the passage of only a few drops of urine are common. Clinical examination must include inspection of the ventral abdomen for edema, inspection and palpation of the preputial orifice for crystals, palpation of the penis in the area of the sigmoid flexure, and inspection and palpation of the urethral process (vermiform appendage) of the exteriorized penis.
If the obstruction is not relieved, urethral rupture or bladder rupture usually occurs within 48 hours. With urethral rupture, the urine leaks into the connective tissue of the ventral abdominal wall and prepuce and causes an obvious fluid swelling, which may spread as far as the thorax. This results in a severe cellulitis and toxemia. The skin over the swollen area may slough, permitting drainage, and the course is rather more protracted in these cases. When the bladder ruptures there is an immediate relief from discomfort but anorexia and depression develop as uremia develops. Two types of bladder rupture have been described; multiple pinpoint perforations in areas of necrosis or discrete tears in the bladder wall. The site of leakage is almost always on the dorsal aspect of the bladder. Complete urethral obstruction therefore results in urethral rupture or bladder rupture and never both in the same animal, because pressure is released once rupture occurs.
A fluid wave is detectable on tactile percussion and the abdomen soon becomes distended. The animal may continue in this state for as long as 2–3 days before death occurs. Fibrin deposition around the dorsal surface of the bladder may be palpated per rectum in steers. In rare cases death occurs soon after rupture of the bladder as a result of severe internal hemorrhage.
In rare cases calculi may form in the prepuce of steers. The calculi are top-shaped and, by acting as floating valves, cause obstruction of the preputial orifice, distension of the prepuce and infiltration of the abdominal wall with urine. These cases may be mistaken for cases of urethral perforation.
Laboratory examinations may be useful in the diagnosis of the disease in its early stages when the calculi are present in the kidney or bladder. The urine usually contains erythrocytes and epithelial cells and a higher than normal number of crystals, sometimes accompanied by larger aggregations described as sand or sabulous deposit. Bacteria may also be present if secondary invasion of the traumatic cystitis and pyelonephritis has occurred.
Serum urea nitrogen and creatinine concentrations will be increased before either urethral or bladder rupture occurs and will increase even further afterwards. Rupture of the bladder will result in uroabdomen. Because urine has a markedly low sodium and chloride concentration and high osmolality relative to plasma, equilibration of electrolytes and free water into the abdomen will always result in hyponatremia, hypochloremia, hyperphosphatemia, and hypo-osmolality in serum, with the magnitude of the changes reflecting the volume of urine in the abdomen. Similar changes in serum biochemistry are present in steers with ruptured urethra, with the magnitude of the changes being smaller than in steers with ruptured bladder.11 Interestingly, steers with ruptured bladder or urethra typically have serum potassium concentrations within the normal range;12 this result most probably reflects the combined effects of increased salivary potassium loss in the face of hyponatremia and inappetance.13
Abdominocentesis is necessary to detect uroperitoneum after rupture of the bladder or needle aspiration from the subcutaneous swelling associated with urethral rupture. However, it is often difficult to identify the fluid obtained from the peritoneal cavity or the subcutaneous tissues as urine other than by appearance and smell, or by biochemical examination. Generally, in uroperitoneum, substantial quantities of fluid can be easily obtained by abdominocentesis. Warming the fluid may facilitate detection of the urine odor, although this is a subjective and poorly sensitive diagnostic test.
Ultrasonography is a useful aid for the diagnosis of obstructive urolithiasis in rams.12 All parts of the urinary tract must be examined for urinary calculi. The kidneys are examined from the paralumbar fossa and the bladder and urethra transrectally. The kidneys are examined for enlargement, and the renal pelves, medullary pyramids and urethra for dilatation. The size of the bladder should be noted and its contents examined. A ruptured bladder does not always empty completely. In rams with obstructive urolithiasis, the urethra and bladder are markedly dilated. Because of severe cystitis, the contents of the bladder appear as multiple, tiny, uniformly distributed echoes. The renal pelves are commonly dilated. Uroperitoneum may also be visualized.
Calculi may be found in the renal pelvis or bladder of normal animals, or of those dying of other diseases. In the renal pelvis they may cause no abnormality, although in occasional cases there is accompanying pyelonephritis. Unilateral ureteral obstruction is usually accompanied by dilatation of the ureter and hydronephrosis. Bilateral obstruction causes fatal uremia. Calculi in the bladder are usually accompanied by varying degrees of chronic cystitis. The urethra or urethral process may be obstructed by one or more stones, or may be impacted for up to 35 cm with a fine sabulous deposit.
When rupture of the urethra has occurred the urethra is eroded at the site of obstruction and extensive cellulitis and accumulation of urine are present in the ventral abdominal wall. When the bladder has ruptured the peritoneal cavity is distended with urine and there is mild to moderate chemical peritonitis. In areas where urolithiasis is a problem it is an advantage to determine the chemical composition of the calculi.
Obstruction of the urethra in ruminant animals is almost always caused by a calculus and is characterized clinically by anuria or dribbling, swishing of the tail, abdominal pain with kicking at the abdomen or stamping the feet, and a progressively worsening condition
Nonobstructive urolithiasis may be confused with pyelonephritis or cystitis, and differentiation may be possible only by rectal examination in the case of vesical calculi or by radiographic examination in smaller animals. Subsequent development of hydronephrosis may enable a diagnosis to be made in cattle. Ultrasonographic examination is useful in sheep
A rectal examination, if possible, may reveal distension of the bladder and dilatation and pulsation of the urethra if the bladder has not ruptured
In adults, rupture of the bladder is usually the result of obstructive urolithiasis, although other occasional causes of urethral obstruction are observed
Rupture of the urethra in cattle is characterized by diffuse swelling of the subcutaneous tissues of the ventral body wall and the skin is usually cooler than normal. It must be differentiated from other causes of swelling of the ventral abdominal wall, including abscesses and herniation of abdominal wall, which can be determined by close physical examination and needle aspiration
Dilatation of the urethral recess in young cattle is characterized by a midline perineal swelling and may resemble pulsation of the perineal urethra in obstructive urolithiasis.8 The urethral recess arises from the junction of the pelvic and spongy parts of the urethra at the level of the ischial arch. A fold of urethral mucosa proximal to the recess acts as a valve to prevent the retrograde flow of urine into the pelvic urethra. An abnormally large urethral recess has been described in a calf.8 In dilatation of the urethral recess, during urination the proximal urethra pulses and the swelling may enlarge slightly. There is no urethral obstruction and urine flows passively from the penis for several minutes after the urethral pulsation ceases. The dilatation can be radiographed using contrast media
The treatment of obstructive urolithiasis is primarily surgical. Cattle or lambs with obstructive urolithiasis that are near the end of their feedlot feeding period and close to being marketed can be slaughtered for salvage if the result of an antemortem inspection is satisfactory. Animals in the early stages of obstruction before urethral or bladder rupture will usually pass inspection at an abattoir. The presence of uremia warrants failure to pass inspection. Rams, bucks, and wethers should all have their glans penis exteriorized and inspected, and the urethral process amputated.
It used to be thought that calculi cannot be dissolved by medical means, but recent studies suggest that administration of specific solutions into the bladder can rapidly dissolve most uroliths. Successful outcomes have occurred following instillation of 30–200 mL of an acetic acid solution (Walpole’s buffer, pH adjusted to 4.3–4.8)14,15 or hemiacidrin solution through a cystotomy catheter;10 hemiacidrin is an acidic gluconocitrate solution with magnesium carbonate that is used for dissolution of magnesium ammonium phosphate and calcium phosphate uroliths in humans. The advantage of hemiacidrin is that it is reportedly less irritating to urothelium than other acids of similar pH.10 The cystotomy tube can be placed surgically or transcutaneously, using abdominal ultrasound. The latter technique involves placement of a 12-French sleeved trocar into the lumen of the bladder, followed by removal of the trocar and placement of a 10-French silicone Foley catheter through the sleeve of the trocar into the lumen of the bladder. The balloon on the Foley catheter is then inflated using 0.9% NaCl, the trocar sleeve removed from the abdomen and the Foley catheter secured to the abdomen.10 The cystotomy catheter provides an alternative route for urine to leave the bladder and is allowed to continuously drip. The cystotomy catheter is occluded for 30 minutes to 2 hours after infusion to retain the solution in the bladder and urethra, after this time the solution is drained from the bladder via the cystotomy tube.10,14,15
In early stages of the disease or in cases of incomplete obstruction, treatment with smooth muscle relaxants such as phenothiazine derivatives (aminopromazine, 0.7 mg/kg of BW) has been tried to relax the urethral muscle and permit passage of the obstructing calculus;16 however treatment efficacy is unknown. Animals treated medically should be observed closely to insure that urination occurs and that obstruction does not recur. However, field observations indicate that these relaxants are ineffective, and it is difficult to believe that smooth muscle relaxants could be efficacious given that the urethral and periurethral tissue contains very little smooth muscle.17 A more rational treatment is infiltration of local anesthetic around the origin of the retractor penile muscles18 or a pudendal nerve block, which would relax the retractor penis muscle and straighten the sigmoid flexure, thereby creating a wider and straighter urethral passageway.17
Normograde hydropulsion is only occasionally successful, although it is frequently used as part of the initial treatment. This technique involves catheterization of the urethral orifice with a suitably sized urinary catheter, and intermittent injection of 0.9% NaCl into the urethra in an attempt to flush out the calculi. Frequently, a gritty feeling is detected during this procedure, and one usually is left with the impression that the procedure is creating additional urethral trauma that may contribute to urethral stricture. Normograde hydropulsion may also pack small crystals more tightly into the urethra. In young ruminants, it can be difficult to exteriorize the glans penis and identify the urethral orifice. Cystotomy and retrograde hydropulsion appear to have a higher success rate than normograde hydropulsion.2
Surgical treatment includes perineal urethrostomy to relieve bladder pressure and for the removal of calculi. This is a salvage procedure and treated animals can be sent to slaughter for salvage when they have recovered sufficiently to pass antemortem inspection. In a series of 85 cases of surgical treatment of urethral obstruction in cattle, only 35% of animals recovered satisfactorily.7 In small ruminants, which invariably have multiple calculi, amputation of the urethral process may restore urine flow but usually provides only temporary relief,2 and the long-term prognosis in sheep and goats is poor19 because there is a high rate of recurrence of obstruction with stricture formation at the urethrostomy site.2 If perineal urethrostomy is unsuccessful, tube cystotomy is indicated. Urethroscopy and laser lithotripsy have successfully dissolved uroliths in a small number of small ruminants20 and one steer21 but the technique is expensive and not widely available. Prepubic urethrostomy has been performed in a small number of small ruminants that have undergone stricture formation following perineal urethrostomy,17 whereas urinary bladder marsupialization offers a simpler surgical method for correction.22 There is one report of erection failure in a male goat as a sequela to obstructive urolithiasis; erection failure was attributed to vascular occlusion of the corpus cavernosum penis.23 Surgical correction of urethral dilatation associated with the urethral recess in cattle has been described.24
A number of agents and management procedures have been recommended in the prevention of urolithiasis in feeder lambs and steers. First, and probably most important, the diet should contain an adequate balance of calcium and phosphorus to avoid precipitation of excess phosphorus in the urine. This is the major difficulty in controlling urolithiasis in feedlot ruminants, because their diets are grain (and therefore phosphorus)-rich. The ration should have a Ca:P ratio of 1.2:1, but higher calcium inputs (1.5–2.0:1) have been recommended. Every practical effort must be used to increase and maintain water intake in feeder steers that have just been moved into a feedlot situation. The addition of salt at the level of 4% of the total ration of feeder calves has been shown experimentally to have this effect on both steers and lambs. Under practical conditions salt is usually fed at a concentration of 3–5%, higher concentrations causing lack of appetite. It is thought that supplementary feeding with sodium chloride helps to prevent urolithiasis by decreasing the rate of deposition of magnesium and phosphate around the nidus of a calculus, but it is possible that salt-related diuresis may also play an important role. Feeding of pelleted rations may predispose to the development of phosphate calculi (such as struvite or apatite) by reducing the salivary secretion of phosphorus.15,20
The control of siliceous calculi in cattle which are fed native range grass hay, which may contain a high level of silica, is dependent primarily on increasing the water intake. The feeding of alfalfa hay is considered to increase urine flow and lower the incidence of urolithiasis but the important reason may be that it contains considerably less silica. As in feedlot animals, water intake can be promoted by supplementing the ration with salt. For yearling (300 kg) steers the daily consumption of 50 g of salt does not prevent the formation of siliceous calculi; at 200 g daily intake the occurrence of calculi is significantly reduced, and at 300 g daily calculus formation is almost eliminated. For calves on native range, providing supplements (‘creep feeds’) containing up to 12% salt is effective in eliminating siliceous calculi. This effect is due to the physical diluting effect of increased water intake promoted by salt supplementation. If the calves consume sufficient quantities of salt to increase the water intake above 200 g/kg BW per day the formation of siliceous calculi will be completely suppressed. Since siliceous calculi form in the last 60 days before weaning, it is recommended that calves on range be started on creep feed without salt well before weaning and, once calves are established on the supplement, that the salt concentration be gradually increased to 12%. It is usually necessary to increase the salt gradually to this level over a period of several weeks and incorporate it in pellets to facilitate mixing.
An alkaline urine (pH > 7.0) favors the formation of phosphate-based stones (struvite, apatite) and calcium-carbonate-based stones. Feeding an agent that decreases urine pH will therefore protect against phosphate-based stones. The feeding of ammonium chloride (45 g/d to steers and 10 g daily to sheep) may prevent urolithiasis due to phosphate calculi, but the magnitude of urine acidification achieved varies markedly depending on the acidogenic nature of the diet. For this reason, urine pH should be closely monitored when adding ammonium chloride to the ration, because clinically relevant metabolic acidosis, depression and inappetence can result from over-zealous administration rates. For range animals, ammonium chloride can be incorporated in a protein supplement and fed at about two-thirds of the above dosage. An acidic urine (pH < 7.0) favors the formation of silicate stones, so ammonium chloride manipulation of urine pH is not indicated in animals at risk of developing siliceous calculi. However, ammonium chloride may prevent the formation of silica calculi in sheep;3 this may have been due to the urine-diluting effects of additional chloride intake.
When the cause of urolithiasis is due to pasture exposure, females can be used to graze the dangerous pastures since they are not as susceptible to developing urinary tract obstruction. In areas where the oxalate content of the pasture is high, wethers and steers should be permitted only limited access to pasture dominated by herbaceous plants. Adequate water supplies should be available and highly saline waters should be regarded with suspicion. Sheep on lush pasture commonly drink little if any water; apparently because they obtain sufficient in the feed. Although the importance of vitamin A in the production of the disease has been decried in recent years an adequate intake should be insured, especially during drought periods and when animals are fed grain rations in feedlots. Deferment of castration, by permitting greater urethral dilatation, may reduce the incidence of obstructive urolithiasis but the improvement is unlikely to be significant.
Oehme FW, Tillmann H. Diagnosis and treatment of ruminant urolithiasis. J Am Vet Med Assoc. 1965;147:1331-1339.
Bailey CB. Silica metabolism and silica urolithiasis in ruminants: a review. Can J Anim Sci. 1981;61:219-235.
Larson BL. Identifying, treating, and preventing bovine urolithiasis. Vet Med. 1996;91:366-377.
Van Metre DC, et al. Obstructive urolithiasis in ruminants: surgical management and prevention. Compend Contin Educ Pract Vet. 1996;18:S275-S289.
1 Bailey CB. Can J Anim Sci. 1981;61:219.
2 Haven ML, et al. Cornell Vet. 1993;83:47.
3 Stewert SR, et al. J Anim Sci. 1991;69:2225.
4 Kallfelz FA, et al. Cornell Vet. 1987;77:33.
5 Poole DBR. Ir Vet J. 1989;42:60.
6 Marsh H, Safford JW. J Am Vet Med Assoc. 1957:342.
7 Gasthuys F, et al. Vet Rec. 1993;133:522.
8 Anderson DE, et al. Can Vet J. 1993;34:234.
9 Ashdown RR. J Agric Sci. 1962;58:65. 71
10 Streeter RN, et al. J Am Vet Med Assoc. 2002;221:546.
11 Donecker JM, Bellamy JEC. Aust Vet J. 1982;23:355.
12 Braun U, et al. Can Vet J. 1992;33:654.
13 Sockett D, Knight AP. Compend Contin Educ Pract Vet. 1984;6:S311.
14 Cockcroft PD. Vet Rec. 1993;132:486.
15 Van Metre DC, et al. Compend Contin Educ Pract Vet. 1996;18:S275-S289.
16 Scheel EH, Paton IM. J Am Vet Med Assoc. 1960;137:665.
17 Stone WC, et al. J Am Vet Med Assoc. 1997;210:939.
18 Baxter GM, et al. J Am Vet Med Assoc. 1992;200:517.
19 Van Weeren PR, et al. Vet Q. 1987;9:76.
20 Halland SK, et al. J Am Vet Med Assoc. 2002;220:1831.
21 Streeter RN, et al. J Am Vet Med Assoc. 2001;219:640.
22 May KA, et al. Vet Surg. 2002;31:251.
Urolithiasis occurs sporadically in horses. The prevalence is low at about 0.04–0.5% of all horse accessions or diagnoses.1 Animals from about 5–15 years of age and older are most commonly affected and 76% are males (27% intact, 49% geldings) and 24% females.1 The uroliths are most commonly in the bladder (cystic) although they also occur in the renal pelvis, ureters, and urethra.2 In most cases, there is a single discrete stone, but a sandy sludge accumulates in cases of paralysis of the bladder. Almost all equine uroliths are composed of calcium carbonate in the form of calcite and their ultrastructure has been examined.3-5
The factors that contribute to urolith formation in horses are not understood. Urine from healthy adult horses is characterized by a substantial quantity of mucoprotein, a high concentration of minerals, considerable insoluble sabulous material, and alkalinity. Equine urine is normally supersaturated with calcium carbonate and crystals of calcium carbonate are usually present;5 this is related in some manner with the occurrence of calcium carbonate uroliths in horses. Nephrolithiasis may arise as a sequel to degenerative or inflammatory processes in the kidney in which inflammatory debris serves as a nidus for calculus formation.6
The clinical findings of urolithiasis in the horse include:
• Stranguria (straining to urinate)
• Pollakiuria (frequent passage of small amounts of urine), hematuria and dysuria (difficult urination)
• Incontinence resulting in urine scalding of the perineum in females or of the medial aspect of the hindlimbs in males
• Painful urination with hematuria associated with cystitis
• Bacterial infection is common.7
The bladder wall may be thickened and large calculi in the bladder may be palpable per rectum, just as the hand enters the rectum. Large calculi may be observed using transrectal ultrasonography6 and cystoscopy. Calculi may also be palpated in the ureters, per rectum, or enlarged ureters may be present.4
In males, urethral calculi may present with signs of complete or partial obstruction that may be confused with colic of gastrointestinal origin. Horses with urethral obstructions make frequent attempts to urinate but pass only small amounts of blood-tinged urine. Unless rupture has occurred, the bladder is grossly enlarged. The calculus can be located by palpation of the penile urethra and by passage of a lead wire or catheter. If a catheter or lead wire is passed, care should be taken to prevent damage to the urethral mucosa. Bladder rupture leads to uroperitoneum but, if the rupture occurs at the neck of the bladder, urine may accumulate retroperitoneally and produce a large, diffuse, fluid swelling that is palpable per rectum. When rupture occurs acute signs disappear and are replaced by depression, immobility and pain on palpation of the abdominal wall. The heart rate rises rapidly and the temperature falls to below normal.
Urinalysis reveals evidence of erythrocytes, leukocytes, protein, amorphous debris, and calcium carbonate crystals.
Renal calculi are frequently bilateral and affected animals have often progressed to chronic renal failure by the time of diagnosis without having displayed signs of urinary tract obstruction.6 A history of chronic weight loss and colic in a horse with renal failure indicates the possible presence of renal calculi. Treatment is supportive as for all cases of chronic renal failure.
Treatment for cystic calculi is surgical removal of the calculus and correction of any defect in the bladder. Perineal urethrotomy has been used for removal of cystic calculi in a gelding.8 Urethral calculi in males are removed through the external urethral orifice or by urethrotomy at the site of obstruction. Recurrence of cystic and urethral calculi is common in the horse, which may be related to the failure to remove all calculi. Some cystic calculi can be removed with the aid of electrohydraulic lithotripsy,9 laser lithotripsy under endoscopic visualization10 or surgery. In large mares with bladder calculi, it is possible to remove the calculi manually by passing a very small hand through the urethra into the bladder and retrieving the calculi after administration of epidural analgesia and sedation. Percutaneous nephrostomy of the right kidney under ultrasonic guidance has been used for short-term diversion of urine in a horse with ureteral calculi.2 Ammonium chloride, at 200 mg/kg BW orally twice daily and decreased at biweekly intervals until a dosage of 60 mg/kg BW is reached, is recommended to maintain the urine pH below 7.0.
1 Laverty S, et al. Vet Surg. 1992;21:56.
2 Byars TD, et al. J Am Vet Med Assoc. 1989;195:499.
3 Newman RD, et al. Am J Vet Res. 1994;55:1357.
4 Diaz-Espineira M, et al. J Equine Vet Sci. 1995;15:27.
5 Mair TS. Res Vet Sci. 1986;40:288.
6 Ehnen SJ, et al. J Am Vet Med Assoc. 1990;197:249.
7 Johnson PJ, Crenshaw KL. Vet Med. 1990;85:891.
8 Hanson RR, Poland HM. J Am Vet Med Assoc. 1995;207:418.
Urethral rents are lesions in the convex surface at the level of the ischial arch in geldings and stallions. The lesions communicate with the corpus spongiosum and cause hemorrhage at the end of urination in geldings or during ejaculation by stallions.1 Stallions do not have hematuria, despite having a lesion identical to that in geldings, presumably because of the lower pressure in the corpus spongiosum of stallions at the end of urination compared to that in geldings.2 The disease is apparently caused by contraction of the bulbospongiosus muscle at the end of urination, with a consequent increase in pressure in the corpus spongiosum and expulsion of blood through the rent. The cause of the rent has not been determined. The diagnosis is confirmed by endoscopic examination of the urethra with visualization of the rent in the urethral mucosa. Treatment of the disease is by temporary subischial urethrostomy and sexual rest. Sexual rest alone was successful in one stallion.1
Tumors of the urinary bladder are common only in cattle, where they are associated with bracken poisoning, but they do occur in other circumstances. For example, 18 cows are recorded in one series, with angioma, transitional epithelial carcinoma and vascular endothelioma being the most common tumors. Abattoir surveys in Canada, the USA, and Australia identified papillomas, lymphomas, adenomas, hemangiomas, and transitional cell tumors occurring at low frequencies in slaughter cattle.1-3 Papillomas appear to be associated with the bovine papillomavirus (BPV-5). Most bladder neoplasms develop from focal areas of hyperplasia within the transitional cell layer and approximately 80% of these can be classified as carcinomas while 17% are papillomas. Because these neoplasms arise from a common site, they can be very similar in gross and histological appearance and very difficult to differentiate.3,4 The immunoenzymatic labeling of intermediate filaments in bovine urinary bladder tumors is an accurate indicator of histogenesis.5
Six cases of bladder neoplasia are also recorded in horses.6 Clinical signs included hematuria, weight loss, stranguria and the secondary development of cystitis.
Congenital defects of the urinary tract
Congenital defects of the urinary tract are not common in farm animals. The most common congenital defect is uroperitoneum in foals following rupture of the urinary bladder.
Developmental abnormalities of the kidneys are classified as renal agenesis, hypoplasia and dysplasia, with agenesis and hypoplasia representing different degrees of the same condition. Renal hypoplasia is defined as a decrease in total renal parenchyma of one-third or more, with a proportionately greater loss of medullary than cortical tissue. The diagnosis of renal hypoplasia is straightforward in neonates but can be difficult to differentiate from renal dysplasia in adults.
Bilateral renal hypoplasia with or without agenesis is recorded in Large White piglets, the piglets being dead at birth or dying in the first 3 months of life.1 Clinical signs exhibited by older pigs included lethargy, shivering, anorexia, diarrhea and a slow rate of growth. The disease was suspected to be inherited in a simple autosomal recessive manner and the basic defect appeared to be failure of development of mesonephric mesenchyme.
Cases of bilateral renal hypoplasia have been recorded in four horses.2 The four horses were 1 day to 3 years of age and had common histories of stunting, poor growth rate, anorexia, depression, and lethargy. Evidence of chronic renal failure was present on clinicopathological examination. Transrectal and transabdominal ultrasonography revealed small kidneys and small renal medulla and pelves and was considered a useful diagnostic test.
Renal dysplasia is defined as disorganized development of the renal parenchyma due to anomalous differentiation. Histologically, renal dysplasia is characterized by persistence of abnormal mesenchymal structures, including undifferentiated cells, cartilage, immature collecting ductules, and abnormal lobar organization.
Renal dysplasia with benign ureteropelvic polyps associated with hydronephrosis has been recorded in a 4-month-old foal.3 Renal dysplasia has also been diagnosed in two adult horses with weight loss, azotemia, hypercalcemia and increased fractional clearance of sodium. Ultrasonographic examination of the kidneys revealed a poor distinction between the cortex and medulla due to a hyperechoic medulla, which was due to fibrosis.4 Histological changes in both horses were indicative of interruption of nephrogenesis after the initiation, but before the complete differentiation, of the metanephric blastema. Renal dysplasia is also reported in foals, both as an apparent spontaneous disease5 and in foals born to mares treated with sulfadimidine, pyrimethamine, and folic acid during pregnancy.6
Congenital renal dysplasia has been recorded in two successive years in a Leicester sheep flock crossbred with Suffolk and Swaledale rams.7 Affected lambs were born alive, were reluctant to stand or move, sucked poorly and had wet coats. Lambs improved with nursing and provision of warmth, but none with clinical signs at birth survived beyond 5 days after birth. At necropsy, the kidneys were bilaterally small with fine intracortical cysts and distinct cortical and medullary zones. An inherited dominant trait with complete penetrance is suspected.
Renal tubular dysplasia has been diagnosed in Japanese Black cattle (wagyu) with renal failure, poor growth and long hooves.8 Calves were undersized at birth and had repeated episodes of diarrhea during the neonatal period. Calves began to show signs of growth retardation from 2–5 months of age but had a normal appetite. Clinicopathological findings included azotemia, increased serum phosphorus concentrations and oliguria. At necropsy, the main lesion was dysplasia of the proximal tubule epithelial cells, with secondary interstitial fibrosis with a reduction in the numbers of glomeruli and tubules in older cattle.9 An autosomal recessive mode of inheritance has been determined associated with a deletion of the paracellin-1 gene on chromosome 1.10 This gene encodes a protein that is part of the tight junction of renal epithelial cells, and this gene deletion is considered to be the cause for the renal tubular dysplasia.9 Heterozygotes are clinically normal and have normal renal function.
In most species this is a common congenital defect. If it is extensive and bilateral the affected animal is usually stillborn or dies soon after birth. In some cases, bilateral defects are compatible with life and clinical signs may not present until the residual nephron mass is gradually exhausted and the animal is adult.11 If it is unilateral no clinical signs appear because of compensatory activity in the other kidney, but in an adult the enormously enlarged kidney may be encountered during rectal examination.
In adult horses, polycystic disease may also be acquired rather than congenital.12 The disease is rare, but affected animals present in varying stages of chronic renal failure.13
A high incidence of renal defects has been recorded in sucking pigs from sows vaccinated during early pregnancy with attenuated hog cholera virus; bilateral renal hypoplasia has been observed as a probably inherited defect in Large White pigs.14 Most polycystic kidneys in pigs appear to be inherited in a polygenic manner15 and have no effect on the pig’s health or renal function. However, there is a record of the defect in newborn pigs in one herd in which it caused gross abdominal distension due to moderate ascites and gross cystic distension of the kidneys and tract. There was no evidence that the disease was inherited in this instance and a toxic origin was surmised.
Isolated cysts occur in the kidneys of all species and are of no clinical significance. The increased availability of ultrasonographic examination of the kidneys of animals facilitates antemortem identification of these cysts. The cysts are usually solitary and unilateral.
Congenital polycystic kidney disease of lambs occurs as an autosomal recessive trait.16 The disease is recognized in Romney, Perendale, and Coopworth sheep in New Zealand. Lambs die at or shortly after birth and there is no apparent sex predisposition. Necropsy examination reveals an abdomen distended by the enlarged kidneys, which contain large numbers of fluid-filled 1–5 mm cysts. There are gross and histological abnormalities of the liver and pancreas. A pathologically similar disease is reported in a Nubian goat.17
Ectopic ureter has been recorded in cattle and horses.18 The condition may be unilateral or bilateral with urinary incontinence present since birth as the major clinical manifestation. Reported neurogenic causes of urinary incontinence in horses include cauda equine neuritis, herpesvirus-1 myelitis, Sudan grass toxicosis, sorghum poisoning, trauma, and neoplasia. Nonneurogenic causes of urinary incontinence in horses include ectopic ureter, cystitis, urolithiasis, hypoestrogenism, and abnormal vaginal conformation.19
The ectopic ureter opens into the urogenital tract at a place other than the bladder such as the cervix, urethra, or vagina. The condition is often complicated by ascending infections, hydronephrosis, and dilatation of the ureter. Definite diagnosis requires excretory urography or endoscopy; visualization of the ureteral openings during endoscopy can be assisted by intravenous administration of phenolsulfonphthalein (0.01 mg/kg BW) or indigo carmine (0.25 mg/kg BW) to impart a red or blue color, respectively, to the urine being produced. Surgical treatment involving ureterovesical anastomosis or unilateral nephrectomy has been successful.
Unilateral and bilateral ureteral defects have been reported in newborn foals.20 The clinical presentation is similar to rupture of the urinary bladder but ureteral defects may be more common in filly foals than in colts.21
Failure of the urachus to close at birth occurs most commonly in foals and is very rare in other species. Patent urachus occurs as three syndromes in foals: congenital and present at birth; acquired and secondary to urachal infection or inflammation; or secondary to severe systemic illness, usually sepsis. As a result of the patent urachus, which during intrauterine life drains urine into the allantoic fluid, urine leaks from the umbilicus. The urine flow varies from a continuous stream during micturition to constant or intermittent dribbling, or a continuous moistening of the umbilical stalk. Healthy foals with congenital patent urachus heal in several days and no specific treatment is required. Formerly, cauterization with phenol or silver nitrate was practiced, but this treatment has the potential to induce necrosis and increases susceptibility to infection.
Foals with patent urachus secondary to umbilical disease usually have an enlarged umbilicus and some have a purulent discharge. Foals that have patent urachus secondary to other umbilical disease might require surgical correction, although most respond to a 7–14-day course of antimicrobials. Foals with patent urachus secondary to systemic disease, usually sepsis, should have their other disease treated aggressively and the urachus allowed to close spontaneously, which it usually does. Ultrasonographic examination of the umbilicus of all foals with patent urachus is essential to determine the extent of disease and presence of intra-abdominal disease. As with all sick foals, the immune status of foals with patent urachus secondary to umbilical or systemic disease should be determined by measurement of serum IgG concentration and foals with low serum IgG concentration should receive a transfusion. Cystitis is an occasional sequel but omphalitis and urachal abscess may also develop as complications. Patent urachus with a perforated urethra has been recorded in a lamb.22
Urachal abscess is discussed as a subgroup of umbilical abscess in Chapter 3. When the infection is localized in the urachus there are usually signs of cystitis, especially increased frequency of urination.23
Umbilical evagination of the bladder has been reported in a neonatal filly.24 The bladder prolapsed through the umbilicus such that the mucosa of the bladder was outermost (bladder eversion). Bladder eversion through the urethra into the vagina and through the vulva occurs in mares immediately after parturition. In this instance care must be taken to not mistake the everted bladder for uterine tissue.25 Correction in both instances is surgical.
Rupture of the bladder is dealt with above, under other causes of uroperitoneum in foals.
An anomalous vas deferens caused a chronic partial urethral obstruction in a 2-year-old Limousin bull, resulting in bilateral hydronephrosis, pyelonephritis of the left kidney, and bilateral ureteral dilatation.26 There are two reports of a ruptured urinary bladder in neonatal calves apparently due to a congenital urethral obstruction that was corrected by passing a urethral catheter. Congenital urethral obstruction with subsequent hydronephrosis and uroperitoneum is reported in a lamb.27
This is recorded rarely in calves and is manifested by failure to pass urine and distension of the patent portion of the urethra.28
Imperfect closure of the external male urethra in a series of newborn lambs is recorded with other neonatal defects including atresia ani and diaphragmatic hernia. No genetic influence was suspected and the cause was unidentified.29
1 Cordes DO, Dodd DC. Pathol Vet. 1965;2:37.
2 Andrews FM, et al. J Am Vet Med Assoc. 1986;189:209.
3 Jones SL, et al. J Am Vet Med Assoc. 1994;204:1230.
4 Ronen N, et al. Vet Rec. 1993;132:269.
5 Zicker SC, et al. J Am Vet Med Assoc. 1990;196:2001.
6 Toribio RE, et al. J Am Vet Med Assoc. 1998;212:697.
7 O’Toole D, et al. J Vet Diagn Invest. 1993;5:591.
8 Ohba Y, et al. Vet Rec. 2001;149:115.
9 Sasaki Y, et al. Vet Rec. 2002;150:628.
10 Ohba Y, et al. Vet Rec. 2001;149:153.
11 Ramsay G, et al. Equine Vet J. 1987;19:243.
12 Bertone JJ, et al. J Am Vet Med Assoc. 1987;191:565.
13 Aguilera-Tejero E, et al. Equine Vet J. 2000;32:167.
14 Wells GAH, et al. Vet Rec. 1980;106:532.
15 Wijeratne WVS, Wells GAH. Vet Rec. 1980;107:484.
16 Johnstone AC, et al. New Zealand Vet J. 2005;53:307.
17 Krotec K, et al. Vet Pathol. 1996;33:708.
18 Pringle JP, et al. Can Vet J. 1990;31:26.
19 Johnson PJ, et al. J Am Vet Med Assoc. 1987;191:973.
20 Divers TJ, et al. J Am Vet Med Assoc. 1988;192:384.
21 Robertson JJ, Embertson RM. Vet Clin North Am Equine Pract. 1988;4:359.
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