JPC SYSTEMIC PATHOLOGY

URINARY SYSTEM

November 2023

U-B10

 

Signalment (JPC # 1290759): Dog

 

HISTORY: Tissue from a sick dog

 

HISTOPATHOLOGIC DISCRIPTION: Kidney and ureter: Moderate to abundant numbers of lymphocytes, plasma cells, and macrophages and low numbers of neutrophils, diffusely infiltrate the suburothelial connective tissue of the ureter and renal pelvis and extend into the interstitium of the medulla and cortex. Within the suburothelial connective tissue, this inflammation is confluent with multiple tertiary lymphoid nodules, which have pale germinal centers. Diffusely the urothelium is either swollen and vacuolated (degeneration), transmigrated by moderate numbers of neutrophils that often form intraurothelial microabscesses, hyperplastic, or multifocally ulcerated and replaced by the similar inflammatory population. Extending from the medulla to the cortex in broad linear bands, abundant fibrous connective tissue mixed with the previously described inflammation, expands the interstitium and surrounds, separates and replaces medullary rays and occasionally glomeruli. Multifocally remaining tubules are variably ectatic and sometimes contain eosinophilic proteinaceous material (proteinosis) or cellular debris. Tubular epithelium multifocally displays one of the following changes: attenuation, swollen with vacuolated cytoplasm (degeneration), shrunken and with a pyknotic nucleus (necrotic), or is lost. Multifocally, glomeruli have one or more of the following changes: mild segmental to global expansion of the basement membranes and mesangium by eosinophilic matrix; adherence of the hyperplastic parietal and visceral epithelium of Bowman’s capsule (synechia); loss of glomerular architecture and marked expansion of the mesangium by collagen (glomerulosclerosis); are surrounded by periglomerular fibrosis, or are shrunken, hyalinized, avascular and hypocellular (obsolescence). Multifocally Bowman’s capsule is markedly dilated with atrophy of the glomerular tuft (glomerulocystic change), or multifocally thickened and surrounded by periglomerular fibrosis. The capsular surface is irregularly undulant (correlating with interstitial fibrosis) and moderately thickened by collagenous connective tissue (fibrosis).

 

MORPHOLOGIC DIAGNOSIS: Kidney: Pyelonephritis, lymphohistiocytic, chronic, diffuse, marked with interstitial fibrosis, glomerulosclerosis, tubular degeneration and loss and capsular fibrosis, breed unspecified, canine.

 

ETIOLOGIC DIAGNOSIS: Bacterial pyelonephritis

 

GENERAL DISCUSSION:

• Pyelonephritis is inflammation of the renal pelvis and parenchyma usually resulting from infection ascending from the lower urinary tract; hematogenous spread is uncommon
• Ascending infections is characterized by inflammation, necrosis, and deformity of calyces; often accompanied by ureteritis and cystitis
• Although cattle do not have a true renal pelvis, due to their multipyramidal renal anatomy, the term pyelonephritis is used for inflammation of the proximal ureter  
• Caused by a variety of organisms, primarily coliform bacteria
• Often bilateral but not necessarily symmetric and more severe at the renal poles
• The acute disease is most commonly seen in sows, occurring postpartum or 3-4 weeks post-breeding
• The chronic form is most commonly seen in cattle and dogs
• Sheep and horses rarely develop pyelonephritis; associated with Chlamydia pecorum in sheep (Westermann et. al, Vet Pathol, 2021)

 

PATHOGENESIS:

• Ascending bacterial infection of the lower urinary tract by endogenous bacteria primarily of the bowel and skin
• Normal urinary tract defense against bacterial infection include the shedding of mature epithelial cells with attached bacteria, mucoproteins on the urothelium which prevent bacterial adherence, goblet cell metaplasia, and phagocytosis by superficial urothelium
• Short urethras, urethral trauma and possible hormonal effects predispose females to urinary tract infections
• Pili assist adhesion of bacteria to urinary epithelium, such as with Corynebacterium renale; type 1 fimbriate E. coli is a potent activator of neutrophils, leading to more scarring than nonfimbriate or P-fimbriate E. coli
• Urine voiding and the innate immune system normally maintain urinary bladder sterility; once these organisms enter the urinary bladder, they grow well in urine with low osmolality or an alkaline pH
• Urinary tract obstruction, urine stasis, urolithiasis, tumors, prostatomegaly, and catheterization all increase the risk of pyelonephritis (Schinkothe et. al, J Vet Diagn Invest, 2023)
• Once infection is established in the urinary bladder, the most significant mechanism causing renal infection is vesicoureteral reflux (retrograde flow of urine up the ureters and into the kidney)– common in puppies; 
  1. Bacteria may be carried as far as the urinary space of glomeruli
  2. May occur with normal micturition, urinary obstruction, and manual compression of bladder
  3. Cystitis may enhance reflux as vesicoureteral valve integrity is compromised by mucosal thickening
  4. Endotoxin can also inhibit normal ureteral peristalsis
• Cystitis and bacterial endotoxins alters normal ureteral peristalsis, causing reverse peristaltic waves, and chronic cystitis may lead to chronic active pyelonephritis
• The renal medulla is susceptible to infections because of its relative hypoxia due to low vasa recta hemotocrit, hypertonicity that inhibits neutrophil phagocytosis, and high ammonia concentration that inhibits complement activation
• Common source of bacterial septicemia in dogs (Elbert and Rissi, J Vet Diagn Invest, 2022)

 

TYPICAL CLINICAL FINDINGS:

• Acute: Fever, abdominal pain, anorexia, hematuria, and dysuria; urinalysis findings are bacteriuria, pyuria, and leukocyte casts
• Chronic: Frequently an incidental finding, but may include polyuria, polydipsia, proteinuria, along with the previously described urinalysis findings and general manifestations of uremia

 

TYPICAL GROSS FINDINGS:

• Acute: Irregular red to gray streaks extending from the renal medulla toward the surface; congestion, hemorrhages, and sometimes abscesses in the renal cortex, with pus in the pelvis (pyonephrosis)
• Chronic: Kidneys become scarred and contracted, focally or multifocally, giving the kidneys a coarsely nodular appearance; firm, pale, and shrunken with an irregular surface; scars extend from capsule to pelvis
• Pigs: The renal poles are preferentially involved and the infection may erupt through the renal capsule, producing retroperitoneal hemorrhage and inflammation
• Cattle: The renal lobes are enlarged, tan, and granular due to interstitial nephritis; the cortex becomes a narrow capsule surrounding large amounts of pus in the calyces

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Acute: Features include purulent inflammation and necrosis of papilla or renal crest (necrotizing papillitis); wedge-shaped hyperemia and suppurative tubulointerstitial nephritis and tubular necrosis; glomeruli and nephrons are usually spared but may become entrapped in the widespread inflammation; bacteria may be in collecting tubules; lesions may be focal or diffuse, in one or both kidneys, or in a single lobule (bovine)
• Chronic: Fibrosis replaces major inflammation, lymphoplasmacytic and neutrophilic interstitial nephritis; tubules may be atrophic and contain casts and pus; periglomerular fibrosis occurs frequently; in advanced cases there is progressive stromal collapse, interstitial fibrosis, and contraction with tubular ectasia and proteinaceous casts; scars extend from the capsule to the pelvis 
• Dogs may accumulate colloid-like material in tubules and glomerular capsules are dilated, producing a “thyroidization” of the kidney 
• Emphysematous pyelonephritis is an uncommon variant caused by gas-forming organisms in diabetic dogs and cats with gas in renal parenchyma, collecting system, or perinephric space

 

ADDITIONAL DIAGNOSTIC TESTS: 

• Urinalysis, urine culture, and radiographs
• Cytology: Mixed inflammation, clusters of renal tubular cells, presence of organisms

 

DIFFERENTIAL DIAGNOSIS: 

• Bacteria that most commonly cause pyelonephritis in dogs

• E. coli – gram negative rod
• Staphylococcus aureus – gram positive cocci, large colony forming
• Fungi are rare causes

 

COMPARATIVE PATHOLOGY: Bacterial etiologic agents commonly isolated:  

• All Species
  • E. coli – gram negative rod
  • Enterobacter spp. – gram negative rod
  • Klebsiella spp. – gram negative rod
  • Proteus spp. – gram negative rod
  • Pseudomonas aeruginosa – gram negative rod
  • Staphylococcus spp. – gram positive cocci, large colony forming
  • Streptococcus spp. – gram positive cocci, large colony forming
• Pigs: Acute disease occurs in sows postpartum or 3-4 weeks postbreeding
  • Actinobaculum suis – gram positive rod
  • Corynebacterium renale – gram positive rod, large colony forming
• Cattle:
  • Corynebacterium renale – gram positive rod, large colony forming; obligate parasite of urinary mucosa
  • C. cystitidis and pilosum – gram positive rod, large colony forming
  • Mycoplasma  spp. – rare
• Rodents:
  • Rat: Pyelonephritis more common in males; Streptococci are most common
  • Mouse: Proteus mirabilis in male MM mice
• NHPs: reported in prosimians, capuchins, squirrel monkeys, baboons, and great apes; macaques used as experimental model
  • Corynebacterium spp.
  • Corynebactrium pseudotuberculosis and Pseudomonas sp. In chimpanzees
• Marsupials:
  • Chlamydia pecorum
     
     

References:

1. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Wiley-Blackwell; 2016:145.
2. Cianciolo RE, Mohr FC. Urinary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. 6th ed. Vol 2. St. Louis, MO: Elsevier; 2016:439-441.
3. Elbert JA, Rissi DR. Neuropathologic changes associated with systemic bacterial infection in 28 dogs. J Vet Diagn Invest. 2022 Jul;34(4):752-756.
4. Schinköthe J, Gerlach K, Ulrich RG, Brehm W. Pyelonephritic end-stage kidney and ureterocutaneous fistula in a Shetland pony. J Vet Diagn Invest. 2023 Sep;35(5):577-580.
5. Snyder, L, Seelig, D. Urinary Tract. In: Raskin RE, Meyer DJ, eds. Canine and Feline Cytology: A Color Atlas and Interpretation Guide. 4th ed. St. Louis, MO: Elsevier; 2023:401-402.
6. Sula MM, Lane LV. The Urinary System. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:739-741.
7. Westermann T, Jenkins C, Onizawa E, Gestier S, McNally J, Kirkland P, Zhang J, Bogema D, Manning LK, Walker K, Pinczowski P. Chlamydia pecorum-Associated Sporadic Ovine Abortion. Vet Pathol. 2021 Jan;58(1):114-122.

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