MICTURITION - SPECIMEN ANSWERS
SESSION 10
1. The nephrotic syndrome may be defined as albuminuria, sufficient to cause hypoalbuminaemia, peripheral oedema and hypercholesterolaemia. Typically protein excretion in excess of 3 g/24 hours is required to produce this condition, although 24 hour protein excretions up to 20 g/24 hours are sometimes seen. At least initially following presentation renal function tends to be relatively well preserved, although some causes of the nephrotic syndrome do result in progressive renal impairment with time. Haematuria is an unusual feature of this condition.
The nephritic syndrome is characterised by the finding of both blood and protein in the urine, hypertension and fluid retention associated with renal impairment. Post streptococcal glomerulonephritis is a cause of the nephritic syndrome but is now no longer commonly seen in the UK. Other causes of the nephritic syndrome include a variety of immunological insults to the kidney, including SLE, Wegener's granulomatosis and Henoch Scholein purpura.
2. Proteinuria can be found in any glomerular lesion and thus may be found in any glomerulonephritis. Interstitial diseases rarely give proteinuria.
Proteinuria can be divided into nephrotic and non-nephrotic range (see answer to Q1). Causes of nephrotic range proteinuria may be divided into primary glomerular disease and glomerular changes secondary to systemic disease. Primary glomerular diseases include minimal change glomerulonephritis, membranous glomerulonephritis and focal segmental glomerulonephritis. System diseases leading to nephrotic range proteinuria include diabetes mellitus (causing diabetic nephropathy) and amyloid deposition within the kidney.
You should refer to a histological text for the changes found in various glomerulonephritis. The histological findings of the three main primary glomerular diseases giving nephrotic range proteinuria are as follows:
Minimal change glomerulonephritis: light microscopy and immunofluorescence would be normal. Electron microscopy will show epithelial cell foot process effacement.
Membranous glomerulonephritis: there is an increase in thickness of the basement membrane with sub-epithelial deposition of electron-dense deposits on electron microscopy. Increased deposition of basement membrane between the sub-epithelial deposits gives the appearance of spikes on silver staining under light microscopy. There is little proliferation but mesangial sclerosis may occur in advanced cases. All glomeruli are involved uniformly.
Focal and segmental glomerulonephritis: this is characterised by sclerosis of some but not all glomeruli. Only a portion of the glomerular tuft is abnormal. In early cases predominantly juxtamedullary glomeruli are involved.
3. Proteinuria should be considered abnormal in a 35 year old patient, although in young adults and children proteinuria in association with a febrile illness or postural proteinuria (proteinuria only present when standing) are possible more benign diagnoses.
Investigations should include assessment of renal function, with measurement of plasma urea and creatinine and creatinine clearances. Quantification of 24 hour protein excretion should be performed. Immunological tests, including autoantibodies, ANCA, Complement levels, plasma and urinary protein electrophoresis (to exclude multiple myeloma, which would be unusual in a patient of this age) are indicated. An MSU should be checked, although urinary tract infection is an unlikely cause of isolated proteinuria.
Renal imaging should be performed and, if the kidneys are normal, consideration given to performing a renal biopsy to establish a definitive histological diagnosis. Most nephrologists would perform a renal biopsy if the proteinuria was significant (> 1 gram/24 hours) or if the proteinuria was associated with haematuria or abnormal renal function.
4. Tissue fluid is regulated by a series of forces known as Starling forces. At the proximal (arteriolar) end of the capillary fluid moves from the vascular space into the interstitium under hydrostatic pressure. Towards the end of the capillary, fluid returns from the intestitial space into the capillaries under the influence of the oncotic pressure within the capillary. Plasma proteins, particularly albumin, are the main factors responsible for the oncotic pressure.
In proteinuric states, where the proteinuria is sufficient to lower plasma albumin, the oncotic pressure within the capillaries would be reduced; thus the driving force to return fluid from the interstitial space into the capillaries is reduced and oedema will result (this is the nephrotic syndrome). Under these circumstances effective hypovolaemia results as fluid leaves the vascular space. This stimulates the renin-angiotensin system and increases aldosterone production, which further retains salt and water, thus perpetuating the oedema.
Certain proteinuric states are associated with chronic renal impairment. Under these circumstances the kidney will not regulate salt and water balance appropriately, with a tendency to salt and water retention. In some renal disease this may be the primary cause of oedema without the need for the proteinuria itself to be sufficiently severe to cause hypopalbuminaemia.
5. In a 26-year-old man with isolated microscopic haematuria the most likely diagnosis is an underlying glomerulonephritis of some form. Bladder malignancy or renal cell carcinoma are extremely unlikely diagnoses in this age group. Renal stones can give microscopic haematuria, although this diagnosis is usually associated with symptoms. Investigations should include assessment of renal function, immunological screening tests, including autoantibody examination and consideration of a renal biopsy to look for an underlying glomerulonephritis. In isolated microscopic haematuria with no proteinuria and normal renal function in this age group, an underlying glomerular disorder may be identified in up to sixty percent of patients.
It is important to exclude urinary tract infection as a cause of haematuria and an MSU should be performed in all age groups and if positive, appropriate treatment given before proceeding to further investigations. Urethritis from a sexually transmitted disease may also give isolated microscopic haematuria and should be considered in the young sexually active age group.
6. Macroscopic haematuria is a recognised feature of IgA nephropathy and typically occurs following upper respiratory tract infections. It is also a recognised feature of transitional cell carcinoma of the bladder. Lupus nephritis rarely gives macroscopic haematuria, although microscopic haematuria is a common accompanying feature because of the underlying glomerulonephritis. Diabetic nephropathy is characterised by progressive proteinuria and neither microscopic nor macroscopic haematuria are typical features.
Session 11
1. The USS demonstrates hydronephrosis (dilation of the pelvicalyceal system) and hydro- ureter. In a 65-year-old man the most likely diagnosis is bladder outflow obstruction secondary to prostatic hypertrophy. In this condition there would be enlargement of the bladder as well and the other kidney would also be affected.
An alternative diagnosis would be ureteric obstruction. This may result from extensive tumours of the bladder, occluding the ureteric orifice, or from extensive prostatic tumour invading and occluding the ureter.
If the patient were a 65-year-old woman, the most likely diagnosis would be obstruction to the urinary tract by a pelvic (gynaecological) malignancy.
Further investigation should be aimed at defining the site of obstruction (i.e. examination of the patient, cystoscopy, imaging CT, retrograde pyelography). Management should include rapid relief of the obstruction - the approach will depend on the site of obstruction; ureteric stent, nephrostomy.
2. The patient has renal impairment but the plasma urea is disproportionately elevated compared to the rise in plasma creatinine. There are signs of volume depletion with hypotension and a decreased jugular venous pressure. Urinary sodium is very low. This patient, therefore, has pre-renal renal failure. These findings would be consistent with dehydration from severe diarrhoea and vomiting or hypovolaemia from a large gastrointestinal haemorrhage. Cardiac failure may give a pre-renal type picture with hypotension and a low urinary sodium but the JVP would be expected to be raised. In established acute renal failure the urea and creatinine rise proportionately and urinary sodium is high. The patient should be resuscitated with intravenous fluids or blood products as appropriate. This should restore circulating volume and blood pressure and the renal function should then correct to normal.
All patients with renal impairment should have imaging of their renal tract with an ultrasound scan and pain abdominal x-ray. In this case one would expect these investigations to be normal. Urine osmolarity in pre-renal failure should be raised as the kidney is maximally concentrating urine in order to try and preserve circulating volume.
3. The most likely diagnosis in this patient is acute tubular necrosis. The urea and creatinine are raised in proportion with each other and the patient is significantly hyperkalaemic. Urine output is low and urine osmolarity approaches that of plasma. On the basis of the electrolytes provided, chronic renal failure cannot be completely excluded, although this would be highly unlikely in a thirty-year-old woman who had just gone through a successful pregnancy.
Urgent therapy is required to correct the plasma potassium, which at this level may cause life threatening cardiac arrhythmia. This would be best achieved by urgent dialysis, although other medical measures to lower serum potassium, including the administration of dextrose and insulin to drive potassium into the cells, should be considered whilst arrangements are being made for dialysis. Correction of acidosis may also be of benefit in this regard. Orally administered resins which will exchange potassium usually for calcium across the gut wall, i.e. calcium resonium, are frequently administered, but are relatively slow to act and should not be considered as adequate treatment in their own right. Dialysis is also likely to be indicated in this patient because of the severity of the uraemia and the oliguria.
Patients with acute tubular necrosis normally recover renal function. In a patient such as this with a single insult, i.e. hypovolaemia, it is highly likely that renal function will recover after a period of dialysis support. Return of renal function, however, can take up to six to eight weeks following such an insult. If, however, the haemorrhage was so severe and the hypotension prolonged without adequate resuscitation it is possible that the patient will have suffered cortical necrosis. In modern practice this is a relatively rare event and unfortunately, when it does occur, leads to irreversible renal damage.
An IVP is of no use in a patient with acute tubular necrosis, as neither the kidneys nor the renal tract will opacify well. The imaging method of choice would be an ultrasound scan.
4. Obstruction to the urinary tract will result in uraemia if the obstruction affects both kidneys or is present in a patient with a single functioning kidney. A patient with two normal kidneys and obstruction from a urinary calculus in one ureter will not become uraemic.
Bladder outflow obstruction, the most common cause of which is prostatic enlargement, effectively obstructs both kidneys and therefore will cause uraemia. Intrinsic bladder tumours and tumours in the pelvis may spread directly into occlude both ureters, in which case uraemia will occur. A urinary calculus in a single functioning kidney will also cause uraemia.
5. The glomerular circulation is unique in the body in having both an afferent and efferent arteriole. The pressure in the glomerular capillary bed and hence glomerular filtration rate is regulated by the tone in both the afferent and efferent arteriole. Angiotensin II acts preferentially on the efferent arteriole causing constriction. This action is particularly important in conditions such as renal artery stenosis and chronic renal failure where efferent arteriole constriction is essential to maintain glomerular capillary pressure and hence glomerular filtration rates. Use of ACE inhibitors in these conditions effectively dilate the efferent arteriole and cause glomerular filtration rates to fall.
Under pathological conditions renal blood flow is maintained by vasodilation induced by vasodilatory prostaglandins. The use of non-steroidal anti-flammatory drugs (inhibitors of cyclo-oxygenase) in such patients will therefore cause relative renal vasoconstriction and a fall in renal blood flow and glomerular filtration rate. Thus these drugs should be used cautiously in patients with chronic renal failure, as they are likely to precipitate a decline in renal function. In addition an idiosyncratic 'allergic reaction' is seen in a small percentage of patients given non-steroidal anti-inflammatory drugs producing an interstitial nephritis and acute renal failure. This is rare and often associated with a peripheral eosinophilia.
Gentamicin is a potential tubular toxin and given in excess amounts will cause acute tubular necrosis. It is principally excreted by the kidney and therefore may accumulate in patients with renal impairment. It is essential when using Gentamicin that drug levels are measured frequently (peak and trough) to ensure appropriate does are given and toxicity is avoided. Toxicity may also be compounded by the co-administration of loop diuretics which concentrate Gentamicin within the tubular cells.
6. A fractional excretion of sodium of 2% is high but can be normal. It is compatible with all of the listed diagnosis other than pre-renal failure in which the fractional excretion should be low (less than 1%). Fractional excretion of sodium may be high in normal individuals who consume large amounts of sodium. It is high in patients with acute tubular necrosis where the tubules are no longer able to absorb sodium and the filtered load is also declining due to a falling GFR. Such patients will usually be oliguric
Patients undergoing an osmotic diuresis, such as those with uncontrolled diabetes or patients receiving loop diuretics, will also have a high fractional excretion of sodium.
Clinical evaluation of the patient is essential to distinguish these possibilities. In addition, urinary output and serum creatinine are required.
