CPCs in Urinary Tract Disease
CPC1 A 26 year old woman with flank pain, fever and rigors
CPC2 A 38 year old with acute renal failure following a road traffic accident
CPC3 A 12 year old boy with oedema of the limbs and face
CPC4 A 38 year old man with hypertension and haematuria
CPC5 A 45 year old man with haemoptysis and declining renal function
CPC6 A 50 year old man with chronic renal failure
CPC7 A 23 year old lady with hypertension
CPC8 A 45 year old man with collapse and excruciating flank pain
CPC9 A 56 year old man with a painful flank mass and haematuria
CPC10 A 70 year old man with gross haematuria

CPC 1- A 26 year old lady with flank pain, fever and rigors
A 26 year old lady with insulin-dependant diabetes presents with a sudden onset of flank pain, malaise, fever and rigors . A mid-stream specimen of urine shows red blood cells and a bacterial count of greater than 100,000 per ml . Sterile urine ‘catch’ is sent for culture and sensitivity and after 2 days grows E. coli .
Increased numbers of white cells were seen on microscopic urinalysis
How do bacteria get to the kidneys (which are normally sterile)?
There are two modes of access for bacteria
1 . Ascending infection from the urethral meatus. This is by far the most common route.
2 . Haematogenous spread . This is unusual and follows the deposition of septic emboli during the course of septicaemia.
Acute pyelonephritis is characterized by multiple collections of neutrophil s, often within tubules. Bacterial colonies may also be readily recognized. The coalescence of these microabscesses may lead to large collections of pus within the parenchyma- a condition known as pyonephrosis.
You can make out mutiple yellow 'seedings'
(mainly in the cortex). These 'seedings' are microscopic abscesses. This man had septicaemia secondary to bronchopneumonia.

What are the causative organisms in acute pyelonephritis?
By far the most common infecting organism is Escherichia coli , although Klebsiella and Proteus species are also common. Two other organisms, Pseudomonas aeruginosa and Streptococcus faecalis , are quite common and troublesome because of their resistance to many antibacterial drugs.
In acute pyelonephritis the tubules are infiltrated by neutrophils. The glomerulus (left) is spared.
What are the risk factors for urinary tract infections?
Any obstructive lesions predispose to ascending infections. An important example of this is reflux uropathy , a disease which begins in childhood and which causes recurrent urinary tract infections and which if uncorrected will lead to chronic renal failure. Stasis or stagnation of urine such as in renal cysts predisposes to infection and patients with diabetes mellitus are also at an increased risk.
Urinary tract infections (especially of the lower urinary tract) are much more common in females, possibly due to the shorter length of the female urethra . Ureteric obstruction which may occur during pregnancy may also increase the incidence of pyelonephritis.
A renal abscess is located in the lower pole of the kidney. A variation of abscess is pyonephrosis where pus distends and fills the collecting system.

Is ‘thyroidisation’ seen in acute pyelonephritis?
‘ Thyroidisation ’ is a term used to describe changes in the tubules seen in chronic pyelonephritis . The tubular epithelium is often flattened and contains dense eosinophilic casts which resemble the colloid seen in thyroid follicles.
Chronic pyelonephritis is a controversial entity. It is true that repeated bacterial infections may cause chronic pyelonephritis but almost identical appearances may be caused by chronic glomerulonephritis (end stage kidney). Other changes seen are tubular atrophy, scarring and glomerulosclerosis .
There is extensive chronic inflammation with fibrosis and glomerulosclerosis in this case of chronic pyelonephritis.
Thyroidisation is not seen.
What is xanthogranulomatous pyelonephritis?
This is a variant of chronic pyelonephritis characterised by accumulation of many lipid-laden macrophages within the interstitial tissue . Grossly, there may be a tumorous mass which is yellow in colour and which may extend into the perirenal fat giving the impression that this is an invasive tumour. The disease is usually unilateral and associated with urinary tract obstruction . It is theorised that it represents an abnormal reaction or a deficiency of, macrophages when they encounter E. coli.
This kidney was removed because all the investigations suggested a renal cell carcinoma.
When it was examined in pathology, the entire lesion was composed of macrophages with purple, foamy cytoplasm.

CPC2 - A 38 year old man with acute renal failure after an accident
A 38 year old road traffic accident victim, with a extensive crush injuries and Glasgow coma scale of 3, develops a rapid decline in renal function over the course of a few days. Examination of the urine shows a high sodium concentration (40 mmol/ L) and a low osmolality (dilute urine). Microscopy shows multiple granular casts and red blood cell casts.
A typical aftermath of a RTA. There are often multiple bone, soft tissue and organ injuries.
The primary treatment in these patients is to follow the ABC of resuscitation.
What is the likely cause of this man’s acute renal failure?
The urinary findings and the microscopic features are those of acute tubular necrosis . These patients have an inability to concentrate urine and after a brief period of polyuria develop oliguria and then anuria. The microscopic appearances are obvious necrosis of tubules with ‘ghost-like’ appearances and in later stages, regenerative changes of tubular epithelium. The granular casts are made up of epithelial cell debris . The glomeruli are usually normal. Supportive therapy and correction of the underlying cause is important and the majority of patients will need temporary dialysis as the tubules recover.
Many of the tubules show vacuolation of the cytoplasm.
Some other tubules are lined by flattened epithelium which represents regenerating epithelial cells.
What are the main causes of acute tubular necrosis and how do they differ?

Tubular necrosis is either a result of direct toxic damage to the tubules or as a result of ischaemic necrosis due to diminution of renal blood flow. In this case, the acute tubular necrosis may be due to a combination of these two factors:- he has suffered shock from extensive trauma and blood loss (ischaemia) and extensive crush injury has released massive amounts of myoglobin which is toxic to the tubules.
In toxic damage (mercury, antifreeze, paraquat), there is obvious necrosis of the tubules.
In ischaemic damage, the distal tubules are predominantly affected and not all nephrons are affected equally.
A variety of microscopic abnormalities may be present (obvious necrosis, fatty degeneration).
Some tubules contain brown coloured casts. These represent myoglobin breakdown products. In RTA victims, acute tubular necrosis may be secondary to ischaemia (if blood loss has been significant) or toxic effects from myoglobin (if crush injuries are severe).
How is acute renal failure classified?

Eosinophils are often seen in interstitial nephritis due to drugs. Can you spot them?
What causes renal papillary necrosis?
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Chronic analgesic related nephropathy
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Diabetes mellitus
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Sickle cell disease
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Hypotensive shock in neonates
Sickle cells may lodge and cause ischaemia of the renal papillae.

CPC 3- A 12 year old girl with marked oedema of the face and limbs
A 12 year old boy develops oedema of the lower limbs and face. Examination of the heart was normal. Blood tests show a low total serum albumin and high serum cholesterol. Urine analysis reveals a massive loss of protein in the urine (more than 3.5 grammes per day). A renal biopsy is performed.
The renal biopsy showed a perfectly normal glomerulus on light microscopy.
Why was the renal biopsy performed?
The renal biopsy was performed because of the clinical features which are those of the nephrotic syndrome
(hypoalbuminemia, hypercholesterolemia, significant proteinuria and oedema). The proteinuria may be selective (loss of low molecular weight proteins such as albumin) or non-selective where larger molecules such as immunoglobulins may be lost. The protein loss of more than 3.5 g per day exceeds the livers ability to synthesise protein. This leads to hypoalbuminaemia and thus to oedema because of lowered oncotic pressure.
The low albumin causes the liver to increase general protein synthesis and these proteins include lipoproteins accounting for the hyperlipideamia. The oedema is worsened by the onset of sodium retention due to secondary hyperaldosteronism (consequent on reduced intravascular volume).
The electron micrograph results gave the answer!
What does the electron micrograph show?

The electron micrograph shows fusion of the epithelial cell (podocyte) foot processes. The basement membrane is normal. These features are those of minimal change disease , epithelial cell disease or nil disease (because the light microscopic appearances are normal).The disease predominantly affects children and is characterized by highly selective proteinuria (i.e. predominantly albumin).
In children presenting with the nephrotic syndrome, by far the most likely cause is minimal change disease and patients will often be given a trial of steroids without having a renal biopsy. In steroid resistant cases, cytotoxic drugs may be given. Complete remission is usual but relapses are common.
There is sclerosis in some glomeruli (focal) and in only part of the glomeruli
(segmental). This is focal and segmental glomerulosclerosis (FSGS) and many believe that cases of minimal change disease which do not respond to therapy may truly represent this condition.
What are the main causes of the nephrotic syndrome?
In children, 80% of cases are caused by minimal change disease. In adults, minimal change disease is still the most common cause (25%) but there are other important causes:
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Membranous nephropathy.
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Focal and segmental glomerulosclerosis (FSGS).
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Membranoproliferative disease with hypocomplimentaemia (MPGN or mesangiocapillary glomerulonephritis).
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Secondary causes
i. Diabetes mellitus
ii. Amyloidosis
iii. Systemic lupus erythematosis

In membranous nephropathy, the capillary loops are thickened ('wire loops') on light microscopy.
What are the complications of the nephrotic syndrome?
The most common complication of the nephrotic syndrome is chronic renal failure. This often depends on what disease is causing the syndrome.
There are however two potentially more acute complications.
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Thrombosis.
Thrombosis of the renal vein is particularly frequent in nephrotic syndrome due to membranous nephropathy.
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Infection especially with Pneumococcus . Such infections commonly present as spontaneous peritonitis without evidence of a perforated viscous.
In membranous nephropathy, electron-dense deposits (made up of immune complexes) are present on the subepithelial side of the basement membrane. Pale grey basement membrane material lies between the deposits.

What are the other broad categories of clinical presentation of glomerulonephritis?
 Nephrotic syndrome
 Nephritic syndrome
 Rapidly progressive renal failure
 Recurrent haematuria
 Chronic renal failure
NOTE: assessment of renal biopsies attempts to do several things, chief among them being assessment of the distribution and nature of the glomerular abnormalities. The tubules, blood vessels and interstitium are also assessed.
If more than 70% of glomeruli in a tissue section are affected, then the disease is DIFFUSE . If it is less than
70% it is FOCAL .
If the whole of a single glomerulus shows the abnormality, then the process is GLOBAL . If only part of the glomerulus is affected then it is SEGMENTAL .
The nature of the glomerular abnormality is then assessed. Is there CELL PROLIFERATION? If so, what type of cell (epithelial, endothelial, mesangial, inflammatory). Is the BASEMENT MEMBRANE normal? Is it thinned or thickened or is it split? Are there any IMMUNE COMPLEXES deposited?
In general, a diagnosis can be reached by assessing these features using a combination of clinical and biochemical details, light microscopy, immunomicroscopy (immunohistochemistry and immunofluorescence) and electron microscopy.

CPC 4- A 38 year old man with hypertension and haematuria
A 38 year old man presents for investigation of haematuria (more accurately described as ‘smokey’) and swelling of his eyelids (periorbital oedema) which is most marked in the morning and which clears gradually as the day goes on. On examination, he is hypertensive and the ‘dipstix’ is positive for blood and urine. He is in good general health but had a bout of ‘tonsillitis’ less than 3 weeks ago.
The urine specimens on the left and in the middle contain blood.
This man has the nephritic syndrome. Can you pick out the defining characteristics present in the history?
The defining characteristics of the nephritic syndrome are:
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Hypertension
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Haematuria
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Intermittent oedema (due to proteinuria and retention of sodium and water
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Some reduction in urinary volume
A renal biopsy showed increased glomerular cellularity and obstruction of the capillary loops by neutrophils.

What is the cause of this man’s nephritic syndrome and how has it come about?
This man has a postinfectious glomerulonephritis aka. acute diffuse proliferative glomerulonephritis . The clues to the diagnosis are the history of a sore throat, the 'smoky urine', nephritic syndrome and the biopsy and EM appearances.
This condition is uncommon in the Western world now, thanks mainly to the effectiveness of antibiotics.
Renal symptoms typically occur 10-18 days after a bout of pharyngitis caused by Group A ß-hemolytic
Streptococcus . There are certain subtypes of these bacteria which are especially 'nephritogenic' . Rarely, the disease may follow a skin or middle ear infection and in the UK, the offending organism is as likely to be another bacteria or virus.
The ‘smoky’ urine is caused by urinary sediment which is composed of red blood cells, white blood cells and casts.
The disease is usually self-limited with good recovery of renal function. However, recent studies have suggested that up to half of the patients may show morphological evidence of chronicity (represented by sclerosed glomeruli).
The biopsy hallmarks of the disease are:
Light microscopy shows diffuse and global glomerular involvement. The glomeruli are hypercellular due to increased mesangial cells and neutrophils within the capillary loops. The endothelial cells are swollen.
Immunohistology shows a granular or ‘lumpy-bumpy’ deposition of IgG and C3 along the basement membrane.
Electron microscopy shows large dome shaped deposits in the subepithelial zone. These correspond to the granular deposits of IgG.
Immunofluorescence shows a granular pattern.
What other diseases may cause the nephritic syndrome?
It is important to remember that the nephrotic and nephritic syndromes are not mutually exclusive. That is that they may coexist together or that a particular disease may cause one or other of the syndromes.
The other main group of glomerular diseases that cause the nephritic syndrome are the membranoproliferative or mesangiocapillary glomerulonephritides. These diseases have, as the name suggests, both cell proliferation and basement membrane abnormalities. In the majority of cases there is no identifiable cause but some cases are associated with SLE, malaria and infective endocarditis amongst others.

Two main forms of this disease exist.
Type 1 disease shows deposits in the mesangium and in the subendothelial space. The disease is associated with low complement levels (hypocomplimentaemia).
Type 2 disease is characterized by the presence of electron-dense material arranged in a ribbon-like pattern within the capillary basement membrane and is also called ‘linear dense deposit disease’ .
Both types of disease will lead ultimately to chronic renal failure although this may be delayed for up to 10 years.
Between immune complex deposition and interposition of mesangial matrix, the basement membrane appears to be split.
This is a silver stain and shows a 'double contour' in the walls of many of the capillary loops.
What is Berger’s disease?
This disease is also known as IgA nephropathy or recurrent haematuria syndrome. The disease is common and affects children and young adults mainly. It is particularly common in certain countries (France, Japan,
Italy). The episodes of haematuria may be associated with infections but also with trauma and vigorous exercise. The disease is characterized by the deposition of IgA and C3 in the mesangium (connective tissue framework) of the glomerulus. This deposition is in a diffuse pattern.
Importantly, only 50% of patients are alive with good renal function 20 years after diagnosis.
This immunofluorescence uses antibodies to detect IgA antibodies and shows a patchy but strong positively.

CPC 5- A 45 year old man with haemoptysis and a rapid decline in renal function
A 45 year old man has several episodes of haemoptysis and becomes extremely unwell over the course of the ensuing week. He is taken to casualty where a chest X-ray shows patchy lung shadows and he is noted to be in acute renal failure (elevated urea, creatinine and potassium). His blood pressure is normal. He is transferred to the ICU for urgent dialysis.
The chest x-ray showed bilateral 'fluffy' infiltrates.
Is there a likely link between the acute renal failure and the haemoptysis?
The clinical features and microscopic findings suggest that this man has
Goodpasture’s syndrome
which describes the association of pulmonary haemorrhage with anti-glomerular basement membrane disease leading to rapidly progressive renal failure.
Some patients have glomerulonephritis alone and some have isolated pulmonary haemorrhage.
Anti-glomerular basement membrane disease usually arises as a complication of a vasculitis but in 30% there is no known precipitating factor. Interestingly 90% of patients possess the HLA-DR2 antigen. In this condition, if the patients require dialysis (as about 70% do), then the outlook is very bleak.
The pulmonary haemorrhage may be life-threatening or it may be more chronic ('waxing and waning') leading to anaemia.
Don’t confuse this condition with Wegener’s granulomatosis which may also cause rapidly progressive renal failure with crescents and pulmonary haemorrhage (that condition is a true vasculitis).

This biopsy in Wegener's granulomatosis shows a necrotising vasculitis with the deposition of pink fibrin in the vessel wall.
What is the immunological abnormality in this disorder?
The immunological hallmark of this disease is the presence of IgG antibodies to a portion of the type IV procollagen in the glomerular basement membrane. These antibodies do not bind exclusively to glomerular basement membrane but also to alveolar basement membranes and in the choroid of the eye .
Other autoantibodies that may be present are Anti-tubular basement membrane in 50% and antineutrophil cytoplasmic antibodies (ANCA) in 30%
The important feature on immunohistology is the presence of IgG (less commonly other types) in a linear, non-granular pattern which outlines the capillary walls in a striking fashion.
Apart from the immunological features, there are two other important pathological points:
(i) Focal, segmental and necrotising glomerulonephritis and
(ii) The formation of crescents
Immunofluorescence on a renal biopsy showed the presence of anti-glomerular basement membrane antibodies.

What is a crescent? What are the causes of crescentic glomerulonephritis?
The crescent is the histological correlate of severe, acute and progressive glomerular damage . The crescent is positioned in the urinary space or Bowman’s space and is composed of macrophages, fibrin and, to a small extent, proliferating epithelial cells (cellular crescents). In chronic disease, these cellular crescents may be replaced by scar tissue to become fibrous crescents.
It is thought that the crescent forms as a reaction to escaped fibrin from the damaged glomerulus (In anti-
GBM disease, the focal necrosis of the glomerulus causes fibrin leakage).
Antiglomerular basement membrane disease is just one cause of glomerulonephritis with crescents. There are many others, the majority of which are associated with the presence of ANCA (anti-neutrophil cytoplasmic antibody) but the absence of anti-GBM antibodies. In rare cases, no immunological abnormality is present
(pauci-immune disease).
Many of the underlying disorders are multisystem diseases such as SLE, haemolytic-uraemic syndrome, microscopic polyarteritis nodosa (pANCA) and Wegener’s granulomatosis (cANCA) although crescents can occur on a background of primary glomerulonephritis such as membrano-proliferative disease.
Rare cases have no underlying cause.
A cellular crescent is present on the left and on the right immunofluorescence against fibrinogen highlights this.
What abnormalities would the lungs show?
The lungs tend to be heavy, firm and dark in colour due to the presence of intra-alveolar haemorrhage. On microscopy, the alveolar septae are thickened with evidence of disintegration or rupture. The alveoli will contain fresh haemorrhage but also hemosiderin as a result of old haemorrhage.

CPC 6- A 50 year old man with chronic failure
A 50 year old man presents with hypertension and chronic renal failure. On examination, he has bilateral massive abdominal masses. Abdominal ultrasound reveals multicystic kidneys bilaterally and also a cystic lesion in the liver. He is referred for dialysis and is ‘worked up’ for the transplant list.
This patient with the same condition has had a transplant.He died from an unrelated cause.
Cysts of various sizes in both the cortex and medulla.
What is the diagnosis?
This is an example of autosomal dominant polycystic kidney disease (ADPKD) or type 1 inherited renal cystic disease. The condition affects adults, is one of the commonest inherited disorders and accounts for 10% of all cases of chronic renal failure. 85% of cases are associated with a mutant gene on chromosome 16p .
Progressive renal failure develops in 50% of cases and these need dialysis and ultimately transplantation. The cysts that are formed may be in both the cortex and the medulla.
What are the extrarenal features of this disease?
This condition has important extrarenal abnormalities which may be responsible for significant morbidity and mortality.
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Saccular aneurysm in the circle of Willis = Berry aneurysm.
What other forms of renal cysts do you know of?
Inherited

Autosomal dominant (adult)

Autosomal recessive (infantile)

Medullary cysts i.
Medullary cystic disease ii.
Medullary sponge kidney iii.
Associated with hereditary syndromes (von Hippel-Lindau)
Acquired

Simple cysts (present in 50% over the age of 50)

Dialysis associated cystic disease
Simple urine filled cysts are very common but are rarely symptomatic.

What are the possible complications of renal cysts?
The consequences depend largely on the size and location of the cysts (and on whether other inherited renal anomalies are present). The most serious consequences are chronic renal failure and hypertension .
Because the cysts contain stagnant urine, they are prone to infection and cause an acute pyelonephritis.
Stagnant urine also predisposes to stone formation .
Rarely, haemorrhage into a cyst may cause an acute abdominal event.
As mentioned before, if the renal cysts are associated with dialysis or the vonHippel-Lindau disease, there is a much increased risk of renal cell carcinoma.
This kidney (which has been cut in two) shows a large solid yellow tumour. The cysts were pre-existing in a patient in haemodialysis for chronic renal failure.

CPC 7- A 23 year old lady investigated for hypertension
A 23year old lady presents for investigation of hypertension. This was noted initially during a preemployment health check. Her blood pressure is currently 170/100 mmHg. There is nil of note in her physical examination apart from a ‘bruit’ audible just to the left of her umbilicus.
Schenatic of angiogram results. There are areas of narrowing of the vessel due to thickening of part of the wall.
What is the likely cause for this lady’s hypertension?
This lady may have renal artery stenosis probably due to fibromuscular dysplasia of the renal artery. Renal artery stenosis is usually unilateral and causes diminished renal blood flow and a reduced glomerular filtration rate. There is an increased amount of renin and thus angiotensin II.
Renal artery stenosis has two main causes. The most common (70%) is the presence of an atherosclerotic plaque.
The remainder of the renal artery may be free of atheroma or it may be extensively involved as in diabetics.
The second major cause of renal artery stenosis is fibromuscular dysplasia (as seen here). This is a set of disorders, commoner in females , which are characterized by fibrous or fibromuscular thickening of the intima or media of the arterial wall.

The kidney on the affected side is small and shows coarse, granular scarring of the capsular surface.This is benign nephrosclerosis. It is as a result of hypertension and leads to its aggravation.
What is the classification of systemic hypertension?
Systemic hypertension is classified under two major categories: essential and secondary . The WHO levels for hypertension are 160 mmHg systolic pressure and 95mmHg diastolic pressure . Borderline hypertension is defined as a systolic pressure between 140 and 160 mmHg and a diastolic pressure between 90 and 95 mmHg.
Essential hypertension accounts for 95% of cases and the mechanisms of causation are poorly understood.
Secondary hypertension, as the name implies, is associated with an underlying disease. The causes of secondary hypertension are many but they are worth excluding especially in a young person. The main causes are:
3.
Other endocrine disease

Phaeochromocytoma (left) with residual adrenal cortex on the right.
Benign hypertension is associated with a long clinical course and in the early stages with little clinical effect.
Malignant hypertension is characterized by rapidly rising blood pressure with the diastolic pressure often rising above 130 mmHg. The disease usually occurs on a background of longstanding benign hypertension but it may arise de-novo . The most important effects of malignant hypertension are on the kidneys
(responsible for 90% of deaths) and the brain. In the brain, the intracranial pressure is increased and people may have headaches, nausea and visual disturbance . The characteristic lesion in malignant hypertension is fibrinoid necrosis of the walls or arterioles and small arteries.
Hyperplasia of the medial cells causes compromise of the lumen in this example of hyperplastic arteriolitis. This change may also be seen in malignant hypertension
(along with fibrinoid change).
Do you know anything of the supposed aetiology of essential hypertension?
The hallmark of essential hypertension is increased tone in the peripheral vessels . The cause of this is unknown but there are several theories.
The prevalence of essential hypertension correlates positively with the dietary intake of sodium (salt) .
Genetic factors play a part in the variations in susceptibility to a high salt intake. There are possible direct effects on the vessels from the sympathetic nervous system or by abnormalities of the sodium and potassium
(and thus calcium) transport system or by abnormal release of vasoconstrictor compounds (such as endothelins) from the vessel walls.

CPC 8- A 45 year old man who collapses with excruciating flank pain
A 45 year old man collapses during morning coffee with excruciating flank pain (“the worst in my life”). He is brought into casualty and given intramuscular pethidine as pain relief . An abdominal X-ray is normal. An abdominal ultrasound shows bilateral hydronephrosis and an echogenic lesion in the mid-ureter. He is asked to drink as much water as possible but with no relief of symptoms, he is sent for ESWL.
This abnormality and one of its consequences is seen (arrowed).
What is the cause of this man’s symptoms? What is ESWL?
This man has ureteric colic . A stone has formed in the kidney and has passed into the ureter where it has blocked the ureter causing back pressure within the kidney. The smooth muscle of the ureter contracts vigorously in an attempt to push the stone out and in so doing causes the excruciating pain.
Many people will pass the stone spontaneously and this is why he was urged to drink plenty of fluid.
Sometimes the stone is too big to pass and needs to be either removed via an urethroscope and basket or it needs to be broken up into smaller pieces. This is accomplished by ESWL (Extracorporeal Shock Wave
Lithotripsy) . High frequency ultrasonic waves fragment the stones and leave the soft tissue of the ureter untouched.
What are renal stones made of?.
Renal stones consist of two main elements:
The main types of stones are:
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Normal urine is supersaturated with calcium oxalate and it is surprising that these types of stones are not even more common.
Factors which predispose to formation of the mucoprotein matrix nidus are infection and stagnation of urine.
Gout is caused by hyperuricemia . If the uric acid is increased in the kidneys (hyepruricosuria), urate stones may develop. Above there are pale fibrillary deposits of urate crystals in soft tissue which are surrounded by a foreign body giant cells. This is a gouty tophus.
What is the pathogenesis of Struvite stones?
These stones are made up of magnesium ammonium phosphate. They occur as a result of the action of urease produced by certain bacteria, most notably Proteus species . The urease splits urea into ammonia and hydroxyl (OH) ions, both of which make the urine alkaline leading to supersaturation of the urine with the stones components. The matrix component is made up of urinary mucoprotein and glycocalyx secreted by the bacteria.
These stones are typically found in females , because of a higher incidence of urinary tract infection. The stones are often large and may fill the pelvis and calyces to form a
‘staghorn’ calculus
. If these stones are not removed, they may have serious consequences leading to a diminished life expectancy.
This kidney shows marked thinning of the parenchyma.
A staghorn calculus was removed from the dilated calyces.

What is the definition of hydronephrosis?
Hydronephrosis is defined as dilatation of the renal pelvis with, ultimately, atrophies of the renal cortex .
If the ureter is dilated, it is termed hydroureter.
Anything which obstructs the flow of urine will cause hydronephrosis. Hydronephrosis is usually bilateral but unilateral obstruction may be caused by a stone, a ureteric or renal pelvis tumour or a bladder tumour at the ureteric orifice. Bilateral hydronephrosis is commonly caused by outflow obstruction due to benign prostatic hyperplasia and less commonly by bladder tumours or urethral strictures. A rare but important cause of bilateral hydronephrosis is retroperitoneal fibrosis, a condition where both ureters become enmeshed in and compressed by dense fibrous tissue. The cause if this condition is not known but it has been associated with methysergide ingestion.
The kidney on the left side (right kidney) is hydronephrotic.

CPC 9- A 56 year man with a painful flank mass and haematuria
A 56 year old man presents with a flank mass which is causing him pain. He has also recently noticed blood in his urine ( hematuria ). On examination, his temperature is 38.2C and he has a plethoric complexion .
Examination of the abdomen reveals a balottable left flank mass which the examiner cannot get above.
He has extensive radiological investigations and undergoes a radical left nephrectomy.
A large round yellow mass is present in the lower pole of the kidney
What is the likely diagnosis?
Given the finding, the most likely diagnosis is renal cell carcinoma.
This man has characteristic signs and symptoms; flank pain, flank mass and haematuria . In patients with this triad of symptoms, the likelihood of the diagnosis being a renal tumour is very high (approx. 90%). Other features in this mans history are the fever which may be caused by prostaglandin release by the tumour and a plethoric complexion which may suggest polycythaemia which may be caused by inappropriate secretion of erythropoietin by the tumour.
Carcinomas of the renal pelvis are transitional cell carcinomas.
They present not with a flank mass but with the early onset of haematuria.

What types of renal cell carcinoma do you know of?
The most common type of renal cell carcinoma is the clear cell carcinoma (depicted above). The clear cytoplasm in these tumour cells is caused by an accumulation of either lipid or glycogen . This typical renal cell carcinoma is characterized by loss of the short arm of chromosome 3p.
There are a number of variants of renal cell carcinoma namely papillary renal cell carcinoma (associated with specific chromosomal abnormalities (loss of Y and trisomy of 7 and 17)), chromophobe renal cell carcinoma (containing cells with poorly stained pink cytoplasm and perinuclear halos) and sarcomatoid renal cell carcinoma (malignant spindle cells and resembling a sarcoma). A rare but highly aggressive form of renal cell carcinoma is collecting duct carcinoma.
A packet of tumour cells with clear cytoplasm is the most common finding in renal cell carcinoma. The clear cytoplasm is due to the accumulation of lipid and glycogen.
Do you know of any predisposing factors for renal cell carcinoma?
Cigarette smoking appears to double the risk and obesity is associated with increased risk.
Von Hippel-Lindau disease , an autosomal dominant cystic kidney disease, is associated with a 28% incidence of renal cell carcinoma. This disease is also associated with tumours of the retina and cerebellum (haemangioblastoma).
Patients with chronic renal failure who are on long-term dialysis invariably develop renal cysts. Acquired dialysis associated cystic disease is associated with a 50 fold increased risk of renal cell carcinoma.
Multiple cysts are present in these kidneys of a patient on long-term haemodialysis

Where does renal cell carcinoma typically spread and what local structure may importantly be involved?
Renal cell carcinoma has a propensity both to local invasion and to distant metastasis. Invasion of the perinephric fat is the single most important prognostic factor in pathological staging. The local structure which may be so importantly involved is the renal vein . The tumour often grows in continuity along the renal vein and may even reach the right atrium . A preoperative renal angiogram is necessary to exclude renal vein invasion.
The most common sites for distant metastases are lungs, bone and regional lymph nodes, although any tissue can be involved. Secondaries in the lung are often large and multiple and are referred to as 'cannonball' metastases .
This tumour has invaded the renal vein (arrowed) and has grown in continuity along it.
Are malignant tumours in children different from those in adulthood?
Typical renal cell carcinomas are almost never seen in childhood. Instead, there are a number of different tumours. The most common of these is the nephroblastoma or
Wilm’s tumour
. These tumours account for
6% of all childhood tumours and are composed of three immature cell types; blastema, stroma and epithelium.
In 10% of cases the tumours are bilateral and children may have other inherited abnormalities especially of the iris and the genitourinary tract. A large number of cases are associated with anomalies of chromosome 11p
(involving the WT1 tumour suppressor gene).
Other rarer tumours in childhood are mesoblastic nephroma, rhabdoid tumour and the clear cell sarcoma (bone metastasising tumour of childhood).
Nephroblastoma with the formation of primitive tubular epithelium amid a diffuse population of blastema cells

CPC 10- A 70 year old man with gross haematuria
A 70 year old man presents with persistent and increasing gross haematuria which has been going on for about
3 months. PR examination reveals an enlarged but smooth prostate. Palpation of the kidneys and a renal ultrasound is normal. He is referred for a cystoscopy where a warty tumour is seen on the left anterior bladder wall. A biopsy is taken.
An IVU was performed and showed a filling defect just where the right ureter (on the left here) inserted into the bladder.
What is the most likely cause for this warty lesion?
This lesion is a transitional cell carcinoma of the bladder. This is the most common form of malignant bladder tumour. It is a common lesion accounting for 5% of malignancies in males and 3% in females. In
Egypt, bladder cancer accounts for 11% of all malignancies. It is a disease which is rare in the first 5 decades of life. From a histological point of view, these tumours can be graded depending on the degree of cellular atypia (Grades 1-3).
Other histological types of bladder cancer include adenocarcinoma and squamous cell carcinoma .
There are benign causes of a warty bladder lesion and these include a transitional cell papilloma and an inverted papilloma.
Haematuria i s an almost universal presenting symptom.

Papillary fronds of transitional cell carcinoma (TCC) are seen on the left.
What are the risk factors for this disease?
The aetiological risk factors for bladder cancer can be considered under two main headings: the action of some specific chemical carcinogen and the effects of chronic inflammation and resulting metaplasia.
The carcinogenic agents include cigarette smoke, cyclophosphamide, ß-naphtylamine (in the dye industry) and analgesics (especially of the renal pelvis).
Chronic inflammation factors include schistosomiasis which is associated with squamous metaplasia and squamous cell carcinoma and cystitis glandularis which may predispose to adenocarcinoma. There is also an increased risk in patients with diverticulae of the bladder.
There are 3 morphological variants of transitional cell carcinoma. What are they?
There are three basic patterns of tumour growth.
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Papillary tumours which are largely invasive
Solid, non-papillary tumours which are generally invasive and
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Flat in-situ tumours which are associated with a field change in the bladder mucosa and may be multiple.
Any combination of these three patterns may be seen.
Cytologically malignant cells sit on an intact basement membrane (arrowed). This is carcinoma in-situ.

What is the difference between superficial disease and deeply invasive disease?
From a clinical standpoint, this is the crucial distinction. Superficial disease is that disease which invades only as far as the lamina propria and this accounts for 70% of cases. These patients are often treated by frequent tumour curettage as very few will die of metastatic disease. Deeply invasive disease implies invasion of the muscle and this portends a much worse prognosis. 50% of these patients will die of metastasis
Even though carcinoma in-situ implies, by definition, no invasion, these lesions have a worse prognosis than superficially invasive disease. These lesions are frequently multifocal and deep muscle invasion will occur in up to 80% of cases.
This tumour fills the bladder and had invaded deeply through the wall.