Patterns of Disease: Kidney 2

Question 1

TUBULOINTERSTITIAL DISEASES

Answer 1

• Cysts
• Acute tubular necrosis (nephrosis)- major cause of renal failure.
• TUBULOINTERSTITIAL NEPHRITIS- usually chronic and seen secondary to a glomerular/vascular/tubular/ascending lesion. Can be diffuse or multifocal, with lymphoplasmacytic or mixed interstitial inflammation.
  eg. Leptospirosis, equine arteritis virus, PRRS (pigs), ‘white spotted kidney’ in cow- originally a glomerular/vascular lesion caused by E. coli.

Question 2

DISEASES SPECIFIC TO INTERSTITIUM

Answer 2

Granulomatous nephritis

Medullary amyloidosis

Question 3

TUBULAR LESIONS: CYSTS

Answer 3

Congenital or acquired.
Congenital can be sporadic or inherited- PKD1 gene (persian cats, cairn and west highland white terriers)- animals with this gene abnormality may also have biliary cysts in the liver.

Cysts can be cortical or medullary.
Variable size.
Often incidental- no clinical signs.

Question 4

ACUTE TUBULAR NECROSIS (TOXIC)

Answer 4

Acute tubular necrosis is most often caused by toxins.
NEPHROTOXIC- injures tubular epithelium
ISCHAEMIC- injures basement membrane as well, causing tubulorrhexis (rupture of renal tubules)- harder to recover from.
Gross- bulging, wet cut surface- oedematous cortex.
Histology- PCT is most affected, typical necrosis with pyknotic to karyorrhexic nuclear debris, sloughing/casts.
MECHANISM- Direct epithelial injury (NEPHROTOXIC)
-Impaired Na reabsorption -> Na in DCT -> RAAS activation -> decreased blood flow to kidneys -> ISCHAEMIA

Question 5

ACUTE TUBULAR NECROSIS- TOXINS

Answer 5

Many potential toxins can cause acute tubular necrosis:
Chemicals- ethylene glycol metabolites (antifreeze)
Drugs- aminoglycosides, cisplatin. Drug toxicity is more common in younger animals.
Plants- containing oxalate, oak tannins, pigweed
Pigments- haemoglobin, myoglobin
Vitamins- vitamin D (increases Ca -> mineralisation)
Bacteria- clostridium perfringens type D, epsilon toxin
Metals- lead, mercury
Miscellaneous- melamine

Question 6

OXALATE NEPHROSIS

Answer 6

Seen with antifreeze poisoning (ethylene glycol toxicity)- toxic metabolites.
Calcium oxalate crystals injure tubules- visible on histological examination of kidney scrape/exhibit birefringence.
Gross lesions are usually NOT significant, though pale, patchy areas can be seen in the cortex.

Question 7

NEPHROTOXIC PIGMENTS

Answer 7

-Haemoglobin, myoglobin- harmless in a healthy kidney but with renal hypoperfusion, can be toxic. Dark urine is produced.

HAEMOGLOBINURIC NEPHROSIS- eg. sheep with copper toxicity (gunmetal blue kidneys)
eg. cow leptospirosis/babesiosis
eg. horse- red maple toxicity
eg. canine babesiosis or autoimmune haemolytic anaemia
Intravascular haemolysis -> erythrocyte destruction -> haemoglobinuria.
Interluminal Hb casts can often be seen on microscopic examination.
Dark kidney, pelvis fat often yellow (icterus)

MYOGLOBINURIC NEPHROSIS- seen with acute and extensive muscle necrosis (rhabdomyolysis- skeletal muscle breakdown)

eg. horse- Monday morning disease/tying up- necrosed myofibres release myoglobin.
eg. others- capture myopathy

Question 8

ACUTE TUBULAR NECROSIS (BACTERIAL)

Answer 8

C. perfringens type D, epsilon toxin.
Seen in sheep.
Targets the DCT, causing VERY RAPID, ACUTE necrosis.
Diagnosis on fresh carcass- the kidneys rapidly autolyse in the healthy animal, so could falsely appear necrosed in a healthy, less fresh carcass.

Question 9

TUBULOINTERSTITIAL LESIONS

Answer 9

Gross: Usually not obvious unless in severe cases-

• Pitted, irregular surface, due to fibrosis of interstitium
• Pale foci- inflammation and fibrosis
• Not as discrete as some other cortical lesions- foci merge together to become more diffuse

Histological: Inflammatory infiltrates- lymphoplasmacytic to mixed.

Question 10

LEPTOSPIROSIS

Answer 10

Tubulointerstitial lesions.
Zoonotic.
Leptospirosis interrogans- many serovars are not host adapted eg. pomona in pigs.
Cause severe disease.
Enter body via mucous membrane breach.
Populate RENAL TUBULES.
Animals often have concurrent liver disease- used diagnostically.
Hard to culture- serology for diagnosis.

Gross: Pale, radiating streaks from cortex, icteric fat in hilus (hyperbilirubinaemia)
Histological: Acute necrosis and haemorrhage, Warthin-Starry stain allows visualisation of leptospires in tubules (black squiggles).

Question 11

CANINE HERPES

Answer 11

Tubulointerstitial lesions.
Affects neonatal puppies, often fatal.
Virally induced vasculitis with necrosis and petechial cortical haemorrhages.
Confirm histologically.

Question 12

FELINE INFECTIOUS PERITONITIS

Answer 12

Tubulointerstitial lesions.
Systemic disease- causes lesions in multiple organs/cavities, and vasculitis.
-Pyogranulomatous to lymphoplasmacytic nephritis.
-Lesions track along vasculature (UNLIKE lymphoma, which can be a differential diagnosis)
-Vasculitis can lead to perivascular inflammation.

Question 13

INTERSTITIAL ONLY LESIONS

Answer 13

• Medullary amyloidosis in cats (other species- glomerulus)- Abyssinians.
• Interstitial granulomatous nephritis eg. cow with hairy vetch toxicosis
  eg. fungal/protozoal/parasitic/mycobacterial infection in dog
  eg. pig stephanurus dentatis (kidney worm)

Granulomatous inflammation- macrophages, multinucleate giant cells.

Question 14

TUBULOINTERSTITIAL LESIONS

Answer 14

Histological appearance:
Tubular dilation 
Attenuation of epithelium
Protein casts in dilated tubule lumens
Interstitial fibrosis

Question 15

PELVIS (ASCENDING) LESIONS

Answer 15

1. Hydronephrosis
2. Pyelonephritis
3. Papillary (medullary crest) necrosis.

Question 16

HYDRONEPHROSIS

Answer 16

RENAL PELVIS DILATION caused by obstruction of outflow.
Unilateral or bilateral- relevant with regards to function- more distal obstructions will block both sides (eg. male cats)
Obstruction- stones, stenosis of ureters etc.
Metabolic abnormalities will be noticed before the pelvic enlargement becomes too severe.

Question 17

PYELONEPHRITIS

Answer 17

Ascends from lower urinary tract.
Mostly seen in females due to shorter, wider urethra.
Seen secondary to GI, genital or dermal contamination.
Targets TUBULES and INTERSTITIUM primarily.
Starts in pelvis (pyelo-) and tracts outwards.
Inflammation and pus seen in pelvis/calyces (bovine)
Destruction can occur across the renal crest.
Lesions can tracck all the way to the outer surface of the kidney (cortex).

Question 18

PAPILLARY (MEDULLARY CREST) NECROSIS

Answer 18

Caused by ischaemic injury.
Associated with NSAIDs, especially in horses (overdose in dogs/cats)
Also secondary to ischaemia for many causes.
No pyelitis- pelvis is normal.

Question 19

NEOPLASIA

Answer 19

EPITHELIAL- Renal carcinoma- most common primary kidney tumour.

• Transitional cell carcinoma- from lower urinary tract.
• German Shepherd dog with cystadenomas or cystadenocarcinomas AND nodular dermatofibrosis.

MESENCHYMAL- uncommon.

ROUND CELL- lymphoma- homogenous pale, soft kidney tissue.

Nephroblastoma- embryological tumour.

Gross appearance is not very diagnostic in most cases- appear as lesions, hard to determine cause without further investigation.

Question 20

END STAGE KIDNEY

Answer 20

Hallmark is FIBROSIS- pale, shrunken, pitted, firm kidney.
Histology- increased fibrous connective tissue with ectatic (dilated)/atrophied tubules and sclerotic (rigid) glomeruli
Common in aged cats and dogs.

Question 21

SEQUELAE/NON-RENAL LESIONS OF RENAL FAILURE

Answer 21

Sequelae- Death due to elevated serum potassium, metabolic acidosis, and/or pulmonary oedema.

Mineralisation of tissues due to increased phosphorous- lungs, gastric mucosa, intercostal pleura (most common), renal tubules.

Uraemic ulcers due to increased BUN/creatinine- glossitis (tongue- bilateral lesions on ventral surface), gastritis.
Leads to small vessel damage.

Fibrinous pericarditis (uncommon)

Question 22

LOWER URINARY TRACT

Answer 22

Ureters -> urinary bladder -> urethra.
Injury/infection can enter via ASCENDING, DESCENDING (from kidney) or DIRECT (from lumen- eg. concentrating metabolites) routes.
Ascending infection is more common than descending.

Defences- Flushing of urine

• Peristalsis
• Inhospitable pH
• Mucous coat
• Immune system

Question 23

LOWER URINARY TRACT LESIONS

Answer 23

-Urolithiasis- most common. Can be obstructive. Calcium oxalate and struvite are the most common stones seen in small animals.

Acute cystitis- bacterial
Chronic cystitis- eg. follicular in dogs
Toxic cystitis- eg. cows with enzootic haematuria (bracken fern poisoning)

Neoplasia- Transitional cell carcinoma (trigone)

• leiomyomas
• lymphoma
• rhabdomyosarcoma