Pathological Affection of Urinary System

Dr. Bikash Puri

M.V.Sc (Veterinary Pathology)

APLASIA OR AGENESIS

• Failure of development of one or both kidney such that there is no recognizable renal tissue.
• It may be unilateral or bilateral (only found in aborted fetuses or stillborn animals.)
• Unilateral renal aplasia is compatible with normal life if the other kidney is normal.
• Incidence: higher in some beagles and Doberman pinschers

Findings:

• There is usually a compensatory hypertrophy of the contra-lateral kidney in these cases.
• Ureter may be absent. If present, the cranial extremity of the ureter begins as a blind pouch.

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Dr. Bikash Puri

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Hypoplasia of Kidney

• Renal hypoplasia designates incomplete development of the kidneys.
• Such that fewer than normal nephrons are present at birth,
• Renal hypoplasia has been documented as an inherited disease in some breed of dog and pigs.
• Hypoplasia can be unilateral or bilateral (rare),
• Reduction in number of glomeruli

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Grossly

• The hypoplastic kidney is smaller than normal, and the reduction in size tends to be fairly uniform
• Affected kidneys are shrunken and pitted
• Capsule is usually thickened and often adhered to the cortex
• The parenchyma is usually grayish in color and tends to be firm.

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Unilateral hypoplastic kidney,

Microscopically,

• There is a reduction in the number of nephrons. This is evident in that there are fewer glomeruli than normal.
• The remaining nephrons are usually hypertrophic.
• The tubules in the medulla are often dilated and their epithelial cells are flattened.
• Also, there is usually considerable interstitial fibrosis which causes separation of the tubules. 

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�1RENAL DYSPLASIA�

• Renal dysplasia is ALTERED STRUTURAL ORGANIZATION RESULTING FROM anomalous differentiation.
• It is usually a congenital alteration
• It may occur unilaterally or bilaterally and its existence may be evident grossly and/or histologically.

Grossly,

• affected kidneys are usually smaller than normal.
• They are usually misshapen and fibrosed and they often contain thick-walled cysts.
• Their ureters are usually tortuous and dilated. 

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Histologically,

• immature glomeruli in adolescent or adult kidneys, collecting tubules ending blindly, or primitive ducts surrounded by concentric layers of mesenchyma

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Ectopic Kidney

• Kidney are misplaced from their normal sub-lumbar location because of abnormal migration during fetal development.
• Occur more frequently in pigs and dogs
• Usually involves in only one kidney
• Structurally and functionally normal
• However, malposition of the ureters predisposes them to obstruction which later may result in hydronephrogenesis

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Fused Kidney

• Also called horseshoe kidney result form the fusion of left and right cranial or left and right caudal poles of the kidneys during nephrogenesis
• This fusion leads to appearance of one large kidney with two ureters

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RENAL FAILURE

• Renal failure refers to the condition resulting from suboptimal renal function and characterized by Azotemia.

Symptoms

• tiredness,
• nausea,
• vomiting,
• pruritis and
• twitching.

Types:

• Acute Renal failure
• Chronic renal failure

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Findings:

• loss of sodium homeostasis resulting in either dehydration or over hydration depending on sodium intake.
• lead to metabolic acidosis and to hyperparathyroidism.
• “Uremic Frosting” As renal mass shrinks, phosphorus retention occurs causing a drop in the concentration of ionized calcium. This stimulates the parathyroid gland to release parathormone which attempts to correct the deficit involving ionized calcium. This renal secondary hyperparathyroidism will eventually result in a renal secondary osteodystrophy and metastatic mineralization. The metastatic mineralization is often referred to as "uremic frosting". 

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Dr. Bikash Puri

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Glomerulonephritis

• It is the inflammation of glomerular tuft.
• If the inflammation is localized to few glomerular it is called multifocal glomerulonephritis.
• However, if all glomeruli are involved it is considered generalized glomerulonephritis.
• It is characterized clinically by hematuria, proteinuria, oliguria and azotemia.

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Etiology

• The exact etiology of glomerulonephritis yet unknown but it is believed to be allergic i.e Antigen-antibody reaction to foreign protein.
• Two mechanisms have been postulated by which antigen antibody reaction is brought about in the kidney.
1. There is production of antibody by the animal to the glomerular basement membrane
2. Deposition of antigen antibody complex (not of renal origin) in the basement membrane beneath the epithelium.
• Glomerulonepritis is often seen as a sequal to bacterial or viral disease elsewhere in the body.

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Types of glomerulonephritis

1. Acute glomerulonephritis:

Grossly:

• Kidney are enlarged and pale
• Capsules which peels easily is tense
• On cortex, red dots indicating the congested glomeruli
• Sometime we can see small hemorrhage on the cortex
• On section, the kidney slightly bulges on the edges.

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Microscopically:

• Enlargement of glomerular tuft with increased number of endothelial and mesangial cells filling the bowman’s space
• In early stage: infiltration of neutrophils and monocytes, appears in glomerulus.
• As disease progress, there is proliferation of epithelial cells in the visceral layer of Bowman’s capsule and some may adhere to the parietal layer of Bowman’s capsule. This eventually forms the “ epithelial crescents’ seen is subacute and chronic cases.
• Thrombosis & necrosis of glomerular capillaries with subsequent hemorrhage in glomerulus

2. Membraneous Glomerulonephritis

• Characterized by diffuse glomerular capillary basement membrane thickening because of the presence of subepithelial immunoglobulin deposits.
• This variation is the most common form of immune complex glomerulonephritis in cats.
• There is increased deposition of (perodic acid schiff) positive material and lesser amount of fibrosis.

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Grossly:

• Affected kidney is enlarged and pale due to fatty changes and increase in interstitial fluid caused by generalized edema
• Later stage, the kidney become shrunken and fibrotics.

Microscopic:

• Thickening, splitting and reduplication of glomerular basement membrane
• Loss of the foot process of the podocytes.
• Swelling and fatty changes of glomerular epithelial cells.

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Membraneous glomerulonephritis

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generalized hyaline thickening of glomerular capillary basement membranes. It can occur in

dogs with dirofilariasis.

The glomerular basement membrane is diffusely thickened. PAS reaction

Membranoproliferative Glomerulonephritis

• Characterized by alteration in the basement membrane as well as proliferation of mesangial and parietal epithelial cells of bowman’s capsule.

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Types of membranoproliferative Glomerulonephritis:

Type I

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• Characterized by immune complex deposition in glomeruli in subendothelial region.

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• Proliferation and swelling of endothelial cells

Type II

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• Usuallly associated with deficiency of 3^rd component of complement (C3)
• Can be inherited or acquired.
• Characterized be immune complex deposition in basement membrane (Lamina densa)

Type III

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• Has not been reported in animals
• Subepithelial deposite of immune complex and disruption of basement membrane.
• Swelling of epithelium and its proliferation forming “epithelial cresent”

Schematic representation of patterns in the two types of membranoproliferative glomerulonephritis.

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In type I there are subendothelial deposits; type II is characterized by intramembranous dense deposits (dense deposit disease)

Gross findings

• Affected kidney enlarged and pale
• Small red spots visible through out the cortex.

Microscopical:

• Enlargement of glomeruli
• Proliferation of mesangial cell
• Uneven thickening of glomerular capillary basement membrane with peripheral portion of glomerulus being severely affected.

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Fig: Abundant periglomerular fibrosis surrounds this hypercellular glomerulus (mesangial cells).

• Adhesions between the epithelial cells of the glomerular tuft and Bowman’s capsule (Synechiae)
• Hypertrophy and hyperplasia of the parietal epithelium lining Bowman’s capsule, deposition of fibrinogen and fibrinous thrombi in glomerular capillaries
• In sever and prolonged cases:
• Bowman’s capsule become thickened, hyalinized and reduplicated
• Proliferation of parietal epithelium, an influx of monoocytes and deposition of fibrin can occur within Bowman’s capsule resulting in formation of glomerular cresecent.

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4. Chronic Glomerulonephritis

Grossly:

• Affected kidney are smaller than normal
• Have rough or pitted contour.
• Kidney become firm and tends to be difficult to incise
• The cut surface tends to be coarse, granular and/or cystic.

Microscopic:

• Enlargement of glomeruli
• Proliferation of mesangial and endothelial cells
• Crescent formation” Hallmark of severely damage glomerular is evident
• Entire glomeruls is replaced by hyaline connective tissue.

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Glomerulosclerosis

• Refer to condition in which glomeruli become firm or hardened
• Usu. found associated with diabetes mellitus but mechanism not exactly known.
• End stage of glomerulonephritis. These glomeruli are hypocellular and essentially non functional
• It can be diffuse or segmental thus appearing as a nodular or segmental hyalinized thickening in affected glomeruli

Grossly:

• Affected kidney smaller than normal
• Kidney pale and firm and cut surface tends to be mottled.

Microscopic

• Glomeruli shrink and become hyalinized because of an increase in both fibrous connective tissue and mesangial matrix and loss of glomerular capillaries.

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Glomerulosclerosis, dog.

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Figure: hypocellularity, shrinkage and hyalinization due to an increase in fibrous connective tissue and mesangial matrix and almost complete loss of glomerular capillaries.

Interstitial Nephritis

• It is the inflammation involving primarily the interstitium of the kidney.
• Characterized by degeneration and necrosis of tubular epithelium, oedema and infiltration of inflammatory cells in interstitium.

Etiology:

• Ochratoxins and citrinine
• Leptospira
• Toxins/poision
• Ketosis
• Immune complex

Grossly:

• Enlargement of kidney
• Necrosis, congestion and haemorrhage of kidney
• Abscess in renal parenchyma in suppurative type.

Microscopic

• Necrosis and degeneration of tubular epithelium
• Infiltration of inflammatory cells like neutrophils, macrophages and lymphocytes in interstitium.

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Fig: Interstitial nephritis, malignant catarrhal fever,

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Multiple, pale-white to gray, discrete interstitial inflammatory cells (lymphoplasmacytic)

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Chronic interstitial nephritis

Diffuse interstitial fibrosis is responsible for the fine pitting of the capsular cortical surface, which is stippled red, the result of bands of fibrous tissue (gray) surrounding islands of renal cortex.

The cortex is pitted and granular because of multiple linear and focal scars, and it is also thinner than normal (atrophic).

Pyelonephritis

• It refers to the inflammation of renal pelvis and renal parenchyma.

Etio-pathogenesis:

• Hematogenous spread of infection from endocarditis.
• Obstruction of urinary tract > reflux of bacterial contaminated urine along ureter > contaminated urine will localize in renal pelvis and later on medulla and there upon > bacterial toxin causes irritation > leading to acute inflammation along with suppuration and necrosis.

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Gross findings:

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1. Congestion, hemorrhage and abscess in renal cortex, pelvis and ureters
2. Pus mix urine in bladder
3. Enlargement of kidney.

Renal calyces in the cow contain suppurative exudate

Microscopic

• Suppurative inflammation of pelvis and kidney parenchyma
• In chronic cases infiltration of lymphocytes, plasma cells and neutrophils
• Atrophy of tubules
• Glomerular capsule are thickened and fibrosed (Peri-glomerular fibrosis)
• Tubules may be distended and contain proteinaceous casts.

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Fig: Intratubular and interstitial inflammation, characterized by infiltrates of principally neutrophils (arrow). Inset: Higher magnification of intratubular neutrophils.

Urolithiasis

• It is a condition in which there is presence of caliculi in the urinary passages.
• These caliculi are formed by the precipitation of urinary solutes and may be found in any part of urinary collecting system including renal pelvis, ureters, urinary bladder and urethra.
• Etiopathogenesis:

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Predisposing factors:

1. Avitaminosis
2. Hyperparathyroidism
3. Bacterial infection
4. Sulfonamide therapy, etc

Transitional epithelium of urinary tract undergoes metaplasia into keratinized stratified squamous epithelium

Exfoliation of keratinized epithelial cells

Serve as a nidus

Deposition of organic and inorganic salt around them.

Urinary caliculi

Gross findings:

• Presence of caliculi in the urinary tract or bladder
• Distention of ureters and urinary bladder
• Hydronephrosis if partial obstruction of urinary passages.

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Microscopic findings:

• Degeneration and necrosis of tubular epithelium
• Haemorrhage
• Proliferation of fibrous tissue.

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Hydronephrosis

• It refers to dilation of renal pelvis and calyces with progressive atrophy of the renal parenchyma and cystic enlargement of the kidney.
• It may be unilateral or bilateral

Etiology:

• Congenital or acquired urinary tract obstruction
• Example of acquired causes are caliculi, cystitis, prostatic enlargement, compression of ureters by neoplasm, acquired urethral strictures.

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Dr. Bikash Puri

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Gross

• Progressive dilatation of renal calyces and pelvis and blunting of the papillae or medullary crests
• In severe case, this may progress to form a large unilocular or multiloular cyst from the affected kidney.

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Fig: Markedly dilated pelvis of each kidney

Fig: Chronic Nephrosis—

loss of medullary tissue and atrophy or even loss of the entire cortex in response to elevated pelvic fluid pressure. Note that this case was so severe that only the renal capsule, which contains clear yellow fluid, remains.

Histological:

• Tubular dilation is the most striking feature with damage occurring in the proximal region of the neuron first.
• In severe case, there is liquefactive necrosis in medulla causing progressive reduction in the medullary parenchyma.

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Cystitis

• It is the inflammation of the urinary bladder
• Clinically manifested by frequent painful micturation and presence of inflammatory cells in the urine.

Etiology:

• Bacterial infection e.g: Corynebacterium renale(cattle), Eubacterium suis (pig), E-coli, Proteus sps., Enterobacter sps, Pseudomonas aeruginosa(Retal flora) indog and cats, etc.
• Mycotic – Candida sp., Aspergillus sp.,) -----sporadically
• Formation and accumulation of uroliths
• Traumatic injury
• Tumor
• Exposure to toxic compounds- blacken fern in cattle ---enzootic hematuria,; treatmentwith cyclophosphamide in dog and cat with neoplastic or immunologic diseases; ingestion of blister beetle---toxic coumpond cantharidin (horse)

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Pathogenesis

• Normally as a rule, bacterial population are flushed out through urine > Obstruction leads to retention of urine > Concentrated urine favours bacterial growth > Invasion of bladder epithelium > production of bacterial toxins > Irritation > Cystitis

Microscopic findings:

• Bladder is diffusely thickened
• Mucous membrane are hyperplastic
• Increase number of globlet cells
• Hypertropy of tunica muscularis
• Fibrosis in lamina propria
• Infiltration of neutrophils, lymphocytes, plasma cells, macrophages at the affected sites

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Gross

• Congestion and haemorrhage of urinary bladder
• Thickening of bladder
• Presence of small nodules on the wall
• In chronic cases there is mild corrugation of mucosa side.

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Fig: Acute cystitis

Patchy areas of ulcerated mucosa are interspersed with areas of hemorrhagic mucosa. Note the subserosalhemorrhages (top).

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Renal Neoplasia

• primary tumors of urinary tract are rare:
• bladder tumors > renal tumors; the reason for this may be the prolonged exposure of the bladder mucosa to urinary carcinogens;
• dogs > cats > other species.
• carcinogen may be involved in some cases, e.g. aromatic hydrocarbons, aniline dyes, tryptophan metabolites;
• in dogs, occurrence of transitional cell carcinoma of the bladder has been associated with exposure to flea and tick insecticide dips (but not shampoos), particularly in overweight animals;
• in cattle, enzootic hematuria , caused by prolonged ingestion of bracken fern in combination with infection by bovine papillomavirus type 2, is associated with a variety of epithelial and mesenchymal neoplasms.

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Renal Neoplasia

1. Primary Epithelial Tumors:
1. Renal adenoma - rare; appears as a small solitary cortical mass.
2. Renal adenocarcinoma – more common than adenoma, particularly in dogs;
• grossly, large compressive mass (up to 20 cm in diameter);
• microscopically: neoplastic cells are in tubular or papillary arrangements;
3. Nephroblastoma (embryonal nephroma) - very common tumor in young pigs and chickens;
• seen mostly as an incidental finding at slaughter house;
• large solitary mass or multiple masses which microscopically resemble fetal kidney; can be benign or malignant.
4. Transitional cell papilloma
• common in animals; can be found in the mucosa of the renal pelvis, ureter or urinary bladder.
5. Transitional cell carcinoma
• the most commonly diagnosed tumor in the urinary bladder of domestic animals;
• frequently metastasizes to regional lymph nodes and lungs.

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Renal Neoplasia

2. Primary Mesenchymal Tumors:
• Fibroma, Leiomyoma, Hemangioma (and malignant counterparts) are rare in domestic animals, except for those tumors associated with enzootic hematuria in cattle.
3. Secondary Tumors - Lymphosarcoma: common tumor that metastasizes to the kidneys and other tissues.

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