1.3 Pathology of the Kidneys

What is the functional unit of the kidney?

Nephron (glomerulus & renal tubules)

What will happen if any portion of the nephron is damaged?

Reduced renal function

Potential progressive damage

What changes are often seen in early stages of kidney disease?

Specific anatomic components targeted by specific insults

(ex: glomeruli in immune-mediated disease)

In more chronic kidney disease what pathological changes are often seen?

Non-specific end-stage responses caused by multiple different insults

What are the portals of entry for renal disease?

Hematogenous (septic embolic nephritis or ischemic necrosis)

Via glomerulus (substances secreted into ultrafiltrate or preformed filtered toxins/metabolites)

Ascending from ureter (extension from lower tract)

What are ascending renal infections from the ureters typically secondary to?

GIT content contamination (diarrhea)

Genital tract contamination (pyometra)

Skin contamination (perivulval dermatitis)

What are some developmental disorders of the kidney?

Renal aplasia (failure of development), hypoplasia, or dysplasia

Ectopic kidneys

Polycystic kidney disease

Fused kidneys

Progressive juvenile nephropathy

Polycystic kidney disease

Genetic disorder characterized by the growth of numerous fluid-filled cysts in the kidneys

Persian cats predisposed

Progressive juvenile nephropathy

Failure of kidney development leading to disease in early life

Glomerulus

Convoluted tuft of fenestrated capillaries supported by a mesangial matrix within Bowman's Capsule

Glomerular filtration barrier

Fenestrated endothelium

Basement membrane

Pedicles of podocytes

Ultrafiltrate (glomerular filtrate)

Fluid formed within the nephron after passing through the glomerulus into Bowman's Space

Immune-mediated glomerulonephritis

Persistent infections or prolonged antigenemia enhance the formation of soluble immune complexes

Complement fixation & associated leukocyte damage occurs

What are some diseases that can cause immune-mediated glomerulonephritis?

FeLV

FIP

Pyometra

Pyoderma

Chronic parasitism

Auto-immune disease or neoplasia

Describe the gross pathological change seen with immune-mediated glomerulonephritis

Pinpoint pale/tan foci in the renal cortex

Describe the microscopic pathology associated with immune-mediated glomerulonephritis

Increased glomerular cellularity with thickened basement membranes

Periglomerular fibrosis

Glomerular amyloidosis

Accumulation of insoluble extracellular protein

Most cases occur secondary to chronic inflammation

Affected glomeruli stain black with iodine on gross pathology

Tubules dilated with protein & eosinophilic homogenous material show on microscopic pathology

Acute suppurative glomerulitis

Bacteria lodge in glomerular & interstitial capillaries

Formation of multiple cortical microabscesses

Random tan/red, raised foci of gross pathology

Leukocytes & bacteria in glomeruli on microscopic pathology

What are some diseases that cause Acute Suppurative Glomerulitis?

Actinobacillus equuli (foals)

Trueperella pyogenes (cattle)

Erysipelothrix rhusiopathiae (pigs)

Corynebacterium pseudotuberculosis (sheep & goats)

What are some consequences of glomerular damage?

Protein losing nephropathy leading to nephrotic syndrome

- loss of protein into ultrafiltrate

Protein losing nephropathy

Leakage of albumin into glomerular filtrate overwhelms resorptive ability of PCT leading to proteinuria

Leads to hypoproteinemia & reduced plasma osmotic pressure

Loss of antithrombin III (anticoagulant)

Nephrotic syndrome

Group of clinical signs and symptoms caused by excessive protein loss in urine

Low protein edema & effusions into body cavities with hypercoagulability & hypercholesterolemia

Acute tubular necrosis

Damage to the renal tubules due to presence of toxins in the urine or ischemia

Most important cause of acute kidney injury

What are the mechanisms of damage to the kidney by nephrotoxins?

Direct damage to tubular epithelium

Production of reactive metabolites that stimulate vasoconstriction (lead to toxin-associated ischemia)

What are the mechanisms of damage to the kidney by ischemia?

Reduced renal perfusion leads to reduced GFR

Results in arteriolar vasoconstriction, worsening the ischemia

*Nephrotoxic & ischemic insults can be synergistic*

How can the renal tubules respond to acute tubular necrosis?

If basement membrane remains, tubules can regenerate (remaining epithelial cells proliferate)

Loss of basement membrane leads to replacement by fibrosis (non-functional)

Regeneration is more likely with toxic damage versus ischemia

What are some causes of acute tubular necrosis?

Drugs (NSAIDs)

Fungal & plant toxins

Ethylene glycol (antifreeze)

Bacterial toxins (Pulpy Kidney Disease)

How can NSAIDs result in acute tubular necrosis?

Reduce prostaglandin synthesis leading to afferent arteriole constriction

Decreased renal perfusion leads to acute tubular & papillary necrosis

Additional risk with dehydration, CHF, or CKD

What are some examples of fungal & plant toxins that can cause acute tubular necrosis?

Mycotoxins (Aspergillus spp.)

Lily (cats)

Grapes & raisins (dogs)

Oak tannins (cattle & horses)

How does ethylene glycol cause acute tubular necrosis?

Readily absorbed from the GIT in dogs, cats & pigs

Oxidized by the liver into toxic metabolites (glycolic acid & oxalate)

Filtered by glomeruli causing direct damage to renal tubules

Antifreeze ingestion or oxalate containing plants can cause

What gross pathological change is seen in acute tubular necrosis due to ethylene glycol toxicosis?

White streaks in the renal cortex

What microscopic pathological change is seen in acute tubular necrosis due to ethylene glycol toxicosis?

Calcium oxalate crystal precipitate in the tubules causing obstruction

What bacteria is the cause of pulpy kidney disease (acute tubular necrosis)?

Clostridium perfringens Type D

Produces epsilon toxin in small ruminants

Toxic damage causes tubular degeneration & necrosis with interstitial edema & hemorrhage

*Need to conduct rapid post mortem (autolysis can obscure lesions)*

What are some inherited abnormalities of renal tubular function?

Primary renal glucosuria

Fanconi Syndrome

Cystinuria

Primary renal glucosuria

Inherited disorder or Norwegian Elkhounds with reduced functional capacity of tubular epithelium to reabsorb glucose

No gross or histological findings present

Predisposes to bacterial infections of lower urinary tract

Fanconi Syndrome

Hereditary defect in tubular reabsorption of protein, glucose, phosphate, & amino acids

Can develop progressive renal insufficiency & renal fibrosis

Basenji dogs are predisposed

Cystinuria

Sex linked inherited tubular defect in male dogs

Predisposes to calculi formation & obstruction of the lower urinary tract

Renal interstitium

Fibrovascular stroma that surrounds the nephron

Tubulointerstitial disease

Primary interstitial disease or interstitial disease secondary to tubular damage

What are some causes of tubulointerstitial disease?

Ascending infection (pyelonephritis)

Hematogenous (E. coli, Leptospira, Canine Adenovirus, FIP)

Secondary to tubular damage (infectious, toxic, immune-mediated)

What renal pathological change is seen with E.coli or Leptospira spp.?

White Spotted Kidney Disease

What renal pathological change is seen with feline infectious peritonitis (FIP)?

Granulomatous necrotizing vasculitis

What gross renal pathology can be seen with chronic interstitial disease?

Nodularity & fine pitting on capsular surface (fibrosis)

White foci & streaks in cortex (inflammation & fibrosis)

What renal histopathological change can be seen with chronic inflammation of the interstitium?

Stain for collagen (blue) showing fibrosis

Lymphocytes & plasma cells present

Describe the blood circulation in the kidney

Renal artery branches into interlobar (between pyramids) > arcuate (at pyramid base, corticomedullary junction) arteries > interlobular (in cortex)

Afferent arterioles branching off lobular arteries feed into glomerular capillaries

End-circulation

What effect does reduced glomerular blood flow have on the remainder of the nephron?

Reduced flow

What are some diseases of the renal vascular system?

Hyperemia & congestion

Hemorrhage

Thrombosis

Infarction

Emboli

Hyperemia

Increased arterial blood flow (acute inflammation)

Congestion

Venous blood pooling (cardiac insufficiency, hypovolemic shock)

What diseases/conditions can lead to renal vascular hemorrhage?

Trauma

Coagulopathies (factor VIII deficiency)

Septicemia (Erysipelas, Streptococcal infection)

Vasculitis (FIP, malignant catarrhal fever)

Vascular necrosis (Canine Herpesvirus)

Embolic bacterial diseases (Actinobacillus spp.)

Disseminated intravascular coagulation (DIC)

Thrombosis

Pathological blood clotting in blood vessels or lymphatics

Virchow's triad

Endothelial injury (Canine Adenovirus, FIP, renal glomerular & cutaneous vasculopathy or endotoxin)

Dynamics of blood flow (stasis or turbulence with cardiac disease or hypovolemia)

Hypercoagulability of blood (inflammation, DIC, glomerulonephritis, glomerular amyloidosis)

Major determinants of thrombosis

Renal infarction

Area of peracute ischemia that undergoes coagulative necrosis

Occlusion of arterial supply or venous drainage

What are some causes of renal infarction?

Emboli/thromboemboli

Vasospasm

Extrinsic compression of a vessel

Traumatic rupture

Endotoxemia

What aspect of the renal vasculature is typically affected by renal infarction?

Interlobular artery (cortex only)

What will occur if the renal or interlobar artery are blocked (renal infarction)?

Cortex & medulla are affected

What are the common origins of renal emboli?

Cardiac mural or valvular thrombi

Endarteritis (parasitic disease)

Neoplastic cell

Bacterial or septic

Hydronephrosis

Dilation of one or both kidneys with fluid

Dilation of the renal pelvis due to obstruction of urine outflow leads to increased pelvic pressure & atrophy of renal parenchyma

Intrapelvic pressure increases & blood vessels collapse

Reduced renal blood flow causes ischemia, tubular loss, & fibrosis

*If unilateral, other kidney may be able to compensate*

What are some predisposing factors to hydronephrosis?

Congenital malformation

Ureteral or urethral blockage

Neurogenic functional disorders

Iatrogenic

Pyelonephritis

Bacterial infection of the renal pelvis with extension into the tubules and interstitium

Most common in sows & cows

Associated with parturition, service, & catheter use

What are some causes of pyelonephritis?

Corynebacterium spp.

E. coli

Staphylococcus spp.

Pseudomonas aeruginosa

Trueperella pyogenes

Papillary necrosis

Destructive process involving the medullary papillae and the terminal renal pyramids

Response of the inner medulla to ischemia

What can cause primary papillary necrosis?

Prolonged treatment or overdose of NSAIDs leading to reduced prostaglandin synthesis, reducing renal blood flow, causing ischemic necrosis

What can cause secondary papillary necrosis?

Reduced vasa recta blood flow due to glomerular disease

Compression of the vasa recta by medullary interstitial disease or compression of the renal papilla

What are some general features of renal neoplasia?

Rarely reported

Usually unilateral

Epithelial, mesenchymal, embryonal, or metastatic

Primary renal tumors are often highly malignant with high level of metastasis

Nephroblastoma

Embryonal kidney tumor with high metastatic rate in dogs <2 years

Found incidentally at slaughter in cattle, pigs, and poultry

Renal Carcinoma

Most common primary renal tumor in older dogs

Large, hemorrhagic, necrotic, & cystic lesions

Over 50% metastasize

Can lead to paraneoplastic syndrome (erythropoietin)

Lymphoma

Malignant tumor of lymph nodes and lymph tissue

Primary or metastatic can impact kidneys