URINARY SYSTEM

KIDNEY: INFARCT

1.    Describe the morphological features of this specimen.
 
The organ shown is the kidney. There is a wedge-shaped subcapsular area of infarct with the broad base at the capsular surface and apex pointing towards the medulla and occluded artery. The infarct is yellow in color and is paler in comparison to the surrounding parenchyma which is dark red in color.

2.    What are its causes?
 
Emboli from:
 
a.    A mural thrombus formed over a recent myocardial infarct.
b.    Thrombotic vegetations on mitral and aortic valves.
c.    Thrombus on a mitral or aortic valve prosthesis.
d.    Thrombus from the left atrium with atrial fibrillation.

END-STAGE KIDNEY (BENIGN NEPHROSCLEROSIS)

The patient died of hypertension-related complications. He has a 30-year-history of hypertension.
 
1.    Describe the morphological features of this specimen.
 
The organ shown is the kidney. It is small and has a finely granular surface. 

2.    What are its pathogenesis?
 
In long-standing benign hypertension, changes in muscular renal arteries and arterioles lead to reduced flow of blood to glomeruli.
 
Renal artery branches within the kidney show thickening of the wall due to fibroelastic intimal proliferation and muscular hypertrophy of the media. Afferent arterioles undergo hyalinizatioin, their muscular walls being replaced by an amorphous material, which is rigid and inelastic. These thickenings of the vessel wall lead to reduction in the size of the lumen and reduced blood flow.
 
Chronic and progressive reduction in blood flow to the nephron leads to chronic ischaemia, with slow conversion of individual glomeruli into a mass of hyaline tissue devoid of capillary lumen. As the renal tubules obtain their blood supply from the glomeruli, they become ischemic too. 
 
Eventually, sufficient numbers of nephrons become non-functioning for the patient to develop manifestations of chronic renal failure.

3.    What are the long-term complications of hypertension?
 
a.    Coronary heart disease.
b.    Cerebrovascular disease.
c.    Renal failure.

HYDRONEPHROSIS

1.    Describe the morphological features of this specimen.
 
The organ shown is the cut section of a bi-halved kidney. The kidney is enlarged and has a cystic appearance. The pelvi-calyceal system is dilated, compressing the surrounding renal parenchyma. There is obliteration of the papillae. There is no sign of calculi in the pelvi-calyceal system or the ureter, strictures or external masses.

2.    What are the causes of this condition?
 
a.    Renal pelvis: calculi, tumor.
b.    Pelvi-ureteric junction: stricture, calculi, extrinsic compression.
c.    Ureter: calculi, external compression by tumor, fibrosis.
d.    Bladder: tumor, calculi.
e.    Urethra: prostatic hyperplasia or carcinoma, urethral valves, urethral strictures.

3.    What will happen if the cause is not removed?
 
Urine formed in the kidney is not able to leave the pelvis and the filtrate subsequently diffuses back into the renal interstitium and perirenal spaces. Because of the continued filtration, the affected calyces and pelvis become dilated. 
 
The unusually high pressure thus generated in the renal pelvis, as well as that transmitted back through the collecting ducts, causes compression of the renal vasculature. Both arterial insufficiency and venous stasis result.
 
This lead to atrophy of renal tubules, glomerular hyalinzation and fibrosis. At an end-stage, the renal parenchyma becomes severely atrophic and renal function is permanently impaired resulting in chronic renal failure.
ACUTE PYELONEPHRITIS

1.    Describe the morphological features of this specimen.
 
The organ shown is the cut section of a bi-halved kidney showing both the external and cut surfaces. The external surface is smooth and shiny and has large wedge-shaped area of coalescent suppuration. The cut surface shows dilated pelvis and calyces and congestion of renal parenchyma. The pelvis is grossly distended and filled with suppurative material. The papillae appears to be pale, soft and hemorrhagic suggestive of papillary necrosis. There are no signs of calculi, or perinephric abscess. These features are consistent with that of an acute pyelonephritis.

2.    What is the pathogenesis?
 
a.    Ascending infection is the most common cause of acute pyelonephritis. The first step is the colonization of the distal urethra by coliform bacteria. From the urethra to the bladder, organisms gain entrance during urethral catheterization or other instrumentation. 
 
b.    Multiplication in bladder: Outflow obstruction or bladder dysfunction results in incomplete emptying and increased residual volume of urine. In the presence of stasis, bacteria introduced to the bladder multiply and grow.
 
c.    Vesicourethral reflux: It is the incompetence of the vesicourethral valve that allows bacteria to ascend the ureter to the pelvis. An incompetent vesicourethral orifice allows the reflux of bladder urine into the ureters. Reflux is most often due to a congenital, inherited absence or shortening of the intravesical portion of the ureter, such that the ureter is not compressed during micturition. 
 
d.    Intrarenal reflux: Vesicourethral reflux propels the infected bladder urine up to the renal pelvis and deep into the renal parenchyma. Intrarenal reflux is most common in the upper and lower poles of the kidney, where papillae tend to be flattened. 

3.    What are the predisposing conditions?
 
a.    Urinary obstruction, either congenital or acquired.
b.    Instrumentation of the urinary tract, e.g. catheterization.
c.    Vesicoureteral reflux.
d.    Pregnancy.
e.    Diabetes mellitus.
f.    Immunosuppression and immunodeficiency.

4.    What complications can it lead to?
 
a.    Papillary necrosis.
b.    Pyonephrosis: the suppurative exudate is unable to drain and thus fills the renal pelvis, calyces and ureter.
c.    Perinephric abscess: extension of suppurative inflammation through the renal capsule into the perinephric tissue.

5.    How would you confirm your diagnosis?
 
Take a midstream urine:
 
a.    Leucocyte esterase and nitrate dipstick to confirm presence of urinary tract infection.
b.    Urine culture: infection is confirmed if > 108 organisms/L.
c.    Urine microscopy: the finding of white cell casts indicate renal involvement because casts are formed only in the tubules.

CHRONIC PYELONEPHRITIS

1.    Describe the morphological features of this specimen.
 
The organ shown is the kidney. The prominent features are the irregular scarring of its surface which is grossly granular. These are features suggestive of chronic pyelonephritis. 

2.    What is the pathogenesis?
 
There are two forms:
 
a.    Chronic obstructive pyelonephritis: Recurrent infections superimposed on diffuse or localized obstructive lesions lead to recurrent bouts of renal inflammation and scarring.
b.    Reflux nephropathy: Renal involvement occurs early in childhood as a result of superimposition of a urinary tract infection on congenital vesicourethral reflux and intrarenal reflux. 

3.    What are the histological features of this condition?
 
The microscopic changes involve predominantly tubules and interstitium:
 
a.    The tubules show atrophy in some areas and hypertrophy in others.
b.    Dilated tubules may be filled with colloid casts.
c.    Chronic interstitial inflammation and fibrosis in cortex and medulla.
d.    Neutrophils in the interstitium and pus casts in the tubules.
e.    Blood vessels: obliterative endarteritis in scarred areas / hyaline arteriosclerosis.

NEPHROLITHIASIS

1.    Describe the morphological features of this specimen.
 
The organ shown is the cut section of a kidney. Its entire calyceal system and pelvis is occupied by a staghorn calculus. There is hydronephrosis with dilatation of the pelvis and calyces with compression of the renal parenchyma into narrow strips between the enlarged calyces. There are no signs of acuate pyelonephritis. 

2.    What are the predisposing factors for this condition?
 
The two main predisposing factors for stone formation are:
 
a.    Increased concentration of solute in urine (low fluid intake or primary increase in metabolite).
b.    Reduced solubility of solute in urine (due to persistently abnormal urinary pH)
 
Conditions that cause these factors are:
 
a.    Low fluid intake.
b.    Urine stasis.
c.    Persistent urinary tract infection.
d.    Primary metabolic disturbances.

3.    What is the main constituent of this lesion? Describe the other possible form(s), if they exist.
 
Staghorn calculi are almost associated with infection. They are likely to be composed of magnesium, ammonium and calcium phosphates (struvite). They are associated with infection in the lower urinary tract as a result of urea-splitting organisms such as proteus, which make urine permanently alkaline.
 
The other two types of urinary stones are:
 
a.    Calcium oxalate or phosphate stones: half of these cases are associated with idiopathic hypercalciuria, the other cases may be caused by hyperoxaluria due to inflammatory bowel disease.
b.    Uric acid stones: predisposed by conditions causing hyperuricemia, e.g. gout.

4.    What complications can it give rise to in the long-term?
 
The presence of calculi in the pelvicalyceal system predisposes to persistent pelvicalyceal infection, pyonephrosis and perinephric abscess, and development of squamous metaplasia in the urothelium. Squamous cell carcinoma may occasionally occur in the metaplastic areas.

5.    What are the clinical manifestations of this condition?
 
a.    A constant ache at the renal angle due to stretching of renal capsule from back pressure effects.
b.    Colicky pain due to referred pain from spasm to ureters.
c.    Low tract irritative type symptoms, e.g. frequency, urgency, hesitancy, caused by bladder and lower ureteric inflammation.
d.    Hematuria.

6.    What investigations will you do?
 
a.    KUB X-ray.
b.    Urine dipstick / Urine analysis tests: reveal presence of hematuria.
c.    IVU: contrast study of urinary system to detect presence of stones and to determine their exact anatomical location.

7.    What can be done in this case?
 
a.    Oral medication: oral dissolution therapy in uric acid stones, alkalinizing agents such as baking soda or potassium citrate.
b.    Surgery: extracorporeal shock wave lithotripsy, percutaneous nephrolithotripsy, uretero-renoscopy. 

BLADDER: TRANSITIONAL CELL CARCINOMA

1.    Describe the morphological features of this specimen.
 
The organ shown is the cut section of a bladder. The prominent feature is a fungating nodular mass that occupies the entire bladder, occluding the lumen. It appears to have invaded deep into the bladder wall and extends beyond it on the surface. These features are consistent with that of transitional cell carcinoma of the bladder.

2.    What are the risk factors for this condition?
 
a.    Cigarette smoking.
b.    Industrial exposure to arylamines, e.g. 2-naphthylamine.
c.    Schistosoma haematobium infections in endemic areas, e.g. Egypt, Sudan.
d.    Heavy long-term exposure to cyclophosphamide.

3.    What is the precursor of this condition?
 
Carcinoma-in-situ is a high grade flat lesion confined to the bladder mucosa. It appears as an area of mucosal reddening, granularity or thickening without producing an evident intraluminal mass. It is commonly multifocal and may involve most of the bladder surface and extend into the ureters and urethra. 

RENAL CELL CARCINOMA

1.    Describe the morphological features of this specimen.
 
The organ shown is the cut section of the left kidney. There is a single large spherical tumor occupying the upper pole of the kidney with smaller satellite nodules scattered elsewhere in the renal parenchyma. The tumor is bright yellow in color and show a variegated cut surface with areas of necrosis and hemorrhage. The tumor-parenchymal interface is sharp. There is gross distortion of the calyces and pelvis with compression of the rest of the renal parenchyma. The tumor appears to be confined within the kidney and has not breached the renal capsule which remains intact. There are no obvious signs of invasion into the renal veins, perirenal fat, adrenal gland and ureter.  

2.    What are the risk factors for this condition?
 
a.    Tobacco: the most prominent risk factor.
b.    Obesity.
c.    Hypertension.
d.    Unopposed estrogen therapy.
e.    Exposure to asbestos, petroleum products, and heavy metals.
f.    Increased in patients with chronic renal failure, acquired cystic disease, tuberous sclerosis and von Hippel-Lindau syndrome. 

3.    What are the clinical manifestations of this condition?
 
a.    Hematuria.
b.    Loin pain.
c.    Varicocele: due to invasion of inferior epigastric vein.
d.    Pathological fractures: due to metastases in bone.
e.    Paraneoplastic syndromes: hypercalcemia, hypertension, polycythemia or Cushing's syndrome caused by ectopic or inappropriate hormone secretion.

4.    What is the prognosis?
 
Prognosis depends on the stage at presentation, e.g. tumor confined within renal capsule has 70% 10-year survival, but very poor prognosis if metastases are present at diagnosis.

5.    What are the associated genetic abnormalities?
 
a.    Clear cell carcinomas: loss of chromosome 3 and 14 sequences.
b.    Papillary carcinoma: trisomy of chromosome 17. 

ADULT POLYCYSTIC KIDNEY DISEASE

The patient is 60-year-old man who died from complications of chronic renal failure. An autopsy was done.

1.    Describe the morphological features of this specimen.
 
The photograph shows a tissue slice from a kidney affected by adult polycystic kidney disease. The kidney is enlarged and there are multiple cysts of varying sizes in all areas of the renal parenchyma. 

2.    What is the etiology of this condition?
 
a.    Genetic, autosomal dominant with high penetrance.
b.    At least two different genes can produce the disease, one being located on the short arm of chromosome 16 (APKD1).

3.    What are the extrarenal manifestations?
 
a.    Hepatic, pancreatic and splenic cysts.
b.    Intracranial and aortic aneurysms.
c.    Cardiac valve abnormalities.

4.    What is the clinical course of this condition?
 
The patients usually present in the 4th to 5th decade of life with progressive renal insufficiency and bilaterally enlarged kidneys, most of which will eventually succumb to renal failure. It is the third most common cause of end-stage renal disease.