Wk 5: Urinary tract and water balance

Portal of entry: Hematogenous bacteremia

Descending bacteremia leads to embolization in the glomerulus, or within interstitial capillaries

▪ neoplastic metastases (tumor emboli)

Portal of entry: ascending from ureter

Ascending bacterial infections from external urethral skin, orifices of the intestinal or genital tracts to the bladder, ureters, and kidneys

Ascending pyelonephritis results in systemic clinical signs(fever, inflammatory leukogram, anemia)

Portal of entry: glomerular filtrate

Toxic substances secreted into the filtrate concentrate and cause injury or ischemia of renal tubular epithelium

Portal of entry: direct penetration

penetrating trauma (cystocentesis)

neoplastic invasion

Renal cysts: incidental finding(one or few)

Spherical, thin-walled distended tubules or Bowman’s space filled with clear watery fluid

tubular dysplasia

pigs and cattle

Polycystic Kidneys

may have impaired function

many cysts affecting numerous nephrons (Swiss cheese appearance)

Who gets polycystic kidneys?

Cairn & West Highland Terriers – often have cystic biliary disease

Autosomal dominant in Persians and bull terriers

Mutations in PKD-1 and/or PKD-2 genes that encode polycystin proteins essential for normal tubulogenesis

embolic glomerulonephritis

Descending hematogenous spread of bacteria (bacteremia) causes bacterial emboli within glomerular capillaries

steps in pathogenesis of GN

Pathogenesis of immune complex glomerulonephritis

Membranous glomerulonephritis

Membranoproliferative glomerulonephritis

Proliferative(endocapillary) glomerulonephritis

Cyst vs pseudocyst

a true cyst has a distinct cellular lining (epithelium), whereas a pseudocyst is surrounded only by scar or granulation tissue without a true cellular wall

Immune complex glomerulonephritis Membranous glomerulonephritis

characterized by diffuse glomerular capillary basement membrane thickening due to

subepithelial deposition of immune complexes and fibrosis

Signs of Immune complex glomerulonephritis Membranous glomerulonephritis

most common form in cats & dogs

Diagnosis: proteinuria (UPC >1.0), histopathology, immunofluorescence for immune complex detection

Glomerulosclerosis

condition of aging, chronic injury, unrestricted high protein diets and high

blood pressure

What happens in glomerulosclerosis?

Glomeruli are shrunken with increased extracellular mesangial matrix leading to obliteration of capillaries and collapse of the glomerular tuft (scarring or sclerosis)

reduces the blood flow to the tubules secondary tubular degeneration and atrophy

Glomerular amyloidosis

Amyloid, insoluble fibrillar protein with β-pleated sheet

amyloidosis commonly causes proteinuria

Who gets glomerular amyloidosis

In domestic animals due to chronic inflammatory diseases reactive systemic amyloidosis (AA amyloidosis) → glomeruli are the most common site

In Abyssinian cats and Chinese Shar-Pei dogs the Medullary interstitium is the common site

Signs of glomerular amyloidosis

Gross lesions: kidneys - enlarged, pale, and have a waxy, smooth, to finely granular capsular surface

Microscopic lesion: deposition of amyloid protein within glomerular tufts

How is the perfusion of the medulla vs. the cortex?

Cortex: blood flow and O2 higher

Outer medulla: blood flow and O2 lower

Physiological and pathophysiological implications of higher perfusion of the cortex?

Physiological: maintain the hyperosmolarity in the medulla → supports the urine concentration capacity of the kidneys.

Inner medulla adapted to low oxygen due to anaerobic glycolysis

nephron injury: toxins can reach the cortex more → higher perfusion and hypoxia

Risks of medullary toxicity

Medullary hypoxic injury leads to tubular necrosis of the corticomedullary and inner medullary nephrons

Too much blood flow or too little disrupts the countercurrent exchange

What can be used during medullary toxicity?

Furosemide is used to reduce GFR and attenuate medullary hypoxia

NSAIDS, antibiotics, Hgb, Mgb, enhances tubular transport and vasoconstriction leading to outer medullary tubular hypoxia and nephrosis

Acute tubular necrosis

Most important cause of AKI

signs include oliguria or anuria with azotemia

Associated with nephrotoxicity or ischemia

Causes of acute tubular necrosis

nephrotoxic pigments - hemoglobin, myoglobin

heavy metals - arsenic, lead

pharmaceutical agents - i.e., NSAIDS

Toxins - bacterial, fungal aflatoxins, plants containing oxalates

Chemicals – ethylene glycol (anti-freeze)

Hemoglobinuric nephrosis (kidneys dark red)

Intravascular hemolysis due to oxidants leads to anemia and excess free Hgb in blood (red plasma)

Hgb passes through glomerular filtrate and exacerbates ischemic injury of the renal tubules

Free Hgb in urine (red urine – UA Heme+)

Hemoglobin casts form (Figure B) and cause renal hypoxia and tubular necrosis

Muscle necrosis releases free myoglobin in

Horses (tying-up syndrome), Capture myopathy in wild animals

Pathogenesis of Nephrotoxic pigments (Myoglobin)

Renal cortices red-brown to blue-black(Figure A) with intratubular myoglobin casts and tubular necrosis (Figure B) → Myoglobin nephrosis

Urine reddish brown (UA – heme+), Muscle enzymes elevated(CK) indicate muscle damage

Differential Diagnosis of Pigmenturia

Pathogenesis of nephrosis due to Heavy metals

Direct injury to tubular epithelial cell membranes and mitochondria

nephrosis due to Heavy metals is important in wildlife diseases and cattle:

Herbicides: arsenic

Lead: used oil, grease, old batteries, machine parts, lead paint, lead shot, environmental contamination by smelting plants

toxicological testing to confirm

Pathogenesis of bacterial pyelonephritis

Inflammation of renal pelvis (pyelitis) with concurrent tubulointerstitial nephritis

Bacterial pyelonephritis: Ascending infection from lower urinary tract more common due to

deranged vesicoureteral junction secondary to obstruction (bacterial toxins, uroliths or stones increase pressure)

recurrent cystitis compromises mucosa and ureteral peristalsis

E. coli with alpha-hemolysin most common toxin

Pyelonephritis: Gross lesions

expansion of the renal pelvis by purulent exudate (pus) and radiating steaks red/pale (see arrows in A: cat and B: cow)

Pyelonephritis: microscopic lesions

suppurative (neutrophilic) inflammation of pelvis with necrotic transitional

epithelium (short arrows) and renal medullary necrosis

Nonsteroidal anti-inflammatory drugs(NSAIDS) decrease?

synthesis of renal prostaglandins responsible for maintaining renal blood flow leads to ischemia and tubular and pelvic(medullary crest) necrosis

NSAIDs in different species

most frequent in horses phenylbutazone, flunixin meglumine (Banamine)

important in dogs/cats due to ingestion(ibuprofen, aspirin, acetaminophen)

When is antifreeze intoxication most common?

Most common in dogs and cats, occasionally pigs, cattle and horse

What does antifreeze ingestion result in?

Ingestion results in nephrotoxic metabolites (oxalates) causes calcium oxalate crystals to form in tubules → Tubular degeneration and obstruction

Infectious causes of interstitial inflammation and renal injury

Leptospirosis, Lyme dis. (common in dogs)

Lymphoplasmacytic infiltrates In interstitium causes tubular necrosis and glomerulosclerosis

Non-infectious causes of interstitial inflammation and renal injury

Chronic kidney disease

Fibrosis leads to tubular necrosis and glomerulosclerosis

Chronic kidney disease (CKD)

Geriatric cats 2X more prevalent than in geriatric dogs

Chronic diseases (i.e., infections, amyloidosis)

Environmental stress

Majority of cats with CKD have

Tubulointerstitial (mononuclear) inflammation and fibrosis with tubular atrophy

Secondary glomerulosclerosis

Atrophy of the kidneys

Renal neoplasia

x < 1% of total neoplasms

unilateral, epithelial, mesenchymal, or metastatic(lymphocytes) in origin

Epithelial tumors

Renal adenoma -rare, clinically asymptomatic

Renal carcinoma: most common primary renal neoplasm

What do epithelial tumors cause?

Typically occurs in older dogs

Paraneoplastic condition (inappropriate erythrocytosis, produce EPO)

Mesenchymal tumors

rare in the kidney

fibromas, fibrosarcomas, or hemangiosarcomas may originate in the kidneys

Hemangiosarcomas have blood-filled cavernous cavities

Metastatic tumors

any metastatic neoplasm (carcinomas/sarcomas) can occur in the kidney

renal lymphoma is a common neoplasm that may be primary or metastatic (most common in cattle and cats)

Nodular/multifocal metastatic tumor

diffuse metastatic tumor

Neoplastic lymphocyte infiltration