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Flashcards in Nephrology Deck (17):
1

In relation to body fluid composition of a 70 kg individual, which of the following values is correct?

Total body water is 42l

The extracellular fluid volume is 15 L representing approximately one third of total body water.

Interstital volume is roughly 11 L (approximately 80% of extracellular fluid), intracellular volume is about two-thirds of total body water (about 28 of the 42 litres of fluid in the body ), plasma volume is 3 L.

2

A severely burned patient is volume depleted and the losses are believed to be due to plasma losses.
Which of the following tests could be used to confirm the suspicion?

Protein-bound dye dilution using Evans blue or iodinated albumin can be used to determine plasma volume.

Creatinine and inulin clearances are measurements of glomerular filtration rate whereas thiosulphate dilution is used to determine the extracellular volume and deuterium dilution is used to determine total body water.

3

Ciclosporin side effect

Ciclosporin causes hypertrichosis rather than alopecia and the most frequent adverse side effect of this drug is nephrotoxicity.

Post renal transplant, the two most common causes of declining renal function are graft rejection and ciclosporin toxicity.

Hepatotoxicity and paraesthesia are less common side effects of the drug. Hypertension can also be seen.

4

A 16-year-old female presents with a three year history of recurrent colicky loin pain. One year ago she passed a renal calculus.
Twenty-four hour urine collection showed normal levels of calcium, phosphate and urate, but elevated levels of arginine, cystine, lysine and ornithine.
Which one of the following features is characteristic of this condition?

This condition is typical of cystinuria (nephropathic cystinosis), an autosomal recessive genetic defect in membrane transport for cystine, lysine, ornithine and arginine in epithelial cells. The glomerus is unable to resorb this amino acids, and they are therefore excretion into the urine. The rBAT gene is responsible, and there are three forms distinguished by the pattern of tubular amino acid transport.

Cystinuria usually presents with recurrent nephrolithiasis, in the form of cystine stones (which are often bilateral and multiple and can form staghorns). These can present as early as the first decade. Renal failure can occur. The stones are radiolucent stones, which may also be seen with uric acid stones. Cystine deposits within the cornea are not classically seen, neither are functional defects within the glomeruli.

Diagnosis of cystinuria can be made by stone analysis - such stones are pale yellow and analysis reveals high cystine levels. It can then be confirmed by an amino acid chromatogram and quantification of cystine excretion.

First line management is conservative, with encouragement of large-volume fluid intake (particularly in the evening, with the aim to pass urine at least once overnight).Urine pH should be regularly monitored (aiming for 7.5-8), with sodium bicarbonate being used if necessary (not in hypertensive patients or those with renal failure). The aim of such treatment is to reduce the urinary cystine concentration to below 300 mg/L. If this fails, d-penicillamine, alpha-mercaptopropionylglycine or captopril can be used.

Cystine stones are not easily broken by lithotripsy, and therefore percutaneous removal is most often used if they do develop.

5

A 65-year-old man presents with renal colic.
The following day he passes a stone in his urine with analysis revealing that it is composed of uric acid.
Which one of the following is the most likely cause of this type of renal stone?

Uric acid stones occur in 5-25% of all cases of nephrolithiasis. They are associated with hyperuricaemia and hyperuricosuria.

Predisposing factors for uric acid stone formation are:

Dehydration
High purine load (high protein diet)
As a primary factor in idiopathic gout, and
Associated with high cell turnover (for example, haematological malignancy).
Allopurinol is prescribed to treat gout and prevents uric acid formation - hence it reduces the frequency of uric acid stones.

Chronic renal failure is incorrect as there is hyperuricaemia without hyperuricosuria.

Hyperparathyroidism is associated with calcium stones, not uric acid stones.

The correct answer is thiazide diuretics. Thiazide diuretics cause hyperuricaemia and can predispose to hyperuricosuria and uric acid stone formation. Uric acid stones are also associated with underlying hypertension. Thiazide diuretics are used to treat calcium stones as they increase the reabsorption of calcium from the proximal tubules, preventing hypercalciuria.

Primary polycythaemia would predispose to uric acid stone formation, whereas secondary polycythaemia does not.

6

A 72-year-old male presented to his GP with depression after the death of his wife.
His notes also reveal that he has a two year history of urinary hesitancy and poor stream.
His GP prescribed him some medication and the following day he developed acute urinary retention.
Which of the following drugs is most likely to have precipitated the urinary retention?

Amitriptyline has anticholinergic effects being associated with tachycardia, dry mouth and urinary retention.

These features are not typical of selective serotonin reuptake inhibitors (SSRIs) such as venlafaxine and fluoxetine with urinary retention and dry mouth rarely reported.

Diazepam, a benzodiazepine does not have anticholinergic effects.

Zopiclone is a benzodiazepine-like agent the side effects of which side effects include drowsiness.

7

Regarding carpal tunnel syndrome (CTS), which of the following is correct?

CTS is associated with conditions such as hypothyroidism, acromegaly and obesity but the vast majority are idiopathic.

Typical symptoms include nocturnal pain in the hand that may radiate up the forearm.

8

Acute tubular necrosis

The hepatorenal syndrome is an intractable form of acute renal failure. Renal recovery is unusual in the absence of liver recovery.

Calcium channel blockers may cause hypotension.

Dopamine infusion has no proven role in acute renal failure in humans, and it may be associated with an increased mortality from vasoconstriction in the mesenteric blood supply.

'Kickstarting' the kidney with furosemide has no role either. It may cause hypotension and thereby prolong ATN. Twenty four hour furosemide infusion has a theoretical role, in that it may limit the oxygen demand and therefore risk of necrosis in the tubules.

ATN is due to ischaemic injury to the kidney and anything that may cause ischaemia may prolong ATN, for example, septic shock.

9

EPO

EPO is released in response to hypoxia (not hypercapnia), anaemia and is mostly synthesised in the kidney - hence requirement in renal failure, although the liver may contribute up to 20% of EPO production.

It specifically stimulates red blood cell (RBC) production and is less effective in iron deficient states.

Side effects include increased blood pressure.

10

Wilms tumour

Is associated with hemihypertrophy
Leukaemias are the commonest cancers in childhood, followed by brain tumours and lymphomas. Neuroblastoma and Wilms' are equal fourth commonest.

Wilms' tumour accounts for most childhood renal neoplasms, and is associated with congenital anomalies such as

Genitourinary abnormalities (4%)
Hemihypertrophy (3%)
Sporadic aniridia (1%).
Deletions on chromosome 11 account for 33% of cases (bilateral cases occur in 10%).

There are three associated syndromes:

WAGR syndrome (Wilms' tumour, aniridia, genitourinary malformations, mental retardation)
Denys-Drash syndrome (Wilms' tumour, nephropathy, genital abnormalities)
Beckwith-Wiedemann syndrome.
Prognosis is generally excellent, with stage 1 disease having a 97% survival, stage 2 disease a 92% survival and stage 3 disease an 87% survival. Stage 4 disease has a 73% survival.

11

renal tubular function

Wilson's disease may lead to amino-aciduria

Aldosterone has its major effect in the distal convoluted tubule.

Creatinine is secreted into the proximal tubule. That is why creatinine clearance is usually higher than the glomerular filtration rate (GFR).

In Wilson's disease it is the toxic effect of copper on the renal tubules that results in aminoaciduria.

The amount of sodium reabsorbed by the start of the distal convoluted tubule is greater than 50%.

PTH causes phosphate excretion.

12

feature which indicates pre-renal uraemia ahead of frank acute tubular necrosis (ATN)?

Urine sodium of 10 mEq/l

A disproportionate rise in plasma urea compared to creatinine suggests pre-renal failure due to hypovolaemia.

In pre-renal failure the urine osmolality is normally greater than 500 mOsm.

Renal failure is partially reversible when adequate renal perfusion is restored.

Protein, red blood cells and cellular casts in the urine suggest intrinsic renal disease.

A urinary sodium of less than 20 mmol/l is suggestive of pre-renal failure. The kidney reabsorption mechanisms are still working at this stage, whilst they fail in established ATN.

13

Ascending loop of henle

This question relates to renal physiology.

The loop of Henle (LOH) employs a sodium counter-current mechanism to provide hypertonic conditions - approximately 1,200 mmol/l, mainly sodium chloride and urea - in the deep medulla of the kidney. This permits the production of concentrated urine if required.

The active component of the LOH is the ascending limb. Here chloride, and hence sodium, are pumped out of the tubule into the interstitium. The ascending limb of the LOH is impermeable to water. The descending limb of the LOH is permeable to sodium chloride and water.

The net effect is for sodium chloride to leave the ascending limb and to enter the descending limb, having first passed through the renal medullary interstitium. Some water is also lost from the descending limb.

As the tubular fluid passes through the ascending limb it becomes increasingly dilute as the sodium chloride is removed. As a result the fluid entering the distal convoluted tubule is hypotonic (150 mmol/l).

14

Retroperitoneal fibrosis is most likely to be associated with which of the following?

Retroperitoneal fibrosis (RPF) is a rare disorder associated with dense fibrosis, producing oedema and biliary and occasionally ureteric obstruction.

Idiopathic RPF normally affects men in their fifth or sixth decade of life.

It is associated with

• Methysergide maleate (migraine medication)
• Riedel's thyroiditis
• Peyronie's disease.

Longstanding infections of the urinary tract, especially with extravasation, can lead to RPF.

15

Nephrotoxic drugs

ACE inhibitors (ramipril and lisinopril) cause renal failure in patients with bilateral renal artery stenosis due to their inhibition of angiotensin II synthesis which results in reduced or even abolished glomerular filtration.

They should be used with caution in patients who may have undiagnosed renovascular disease due to risks of renal impairment.

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit renal prostaglandin synthesis and may result in sodium retention, reduced renal blood flow and renal failure.

Cephalosporins are excreted by the kidneys and their dose should be reduced in patients with moderate to severe renal impairment and may cause a reversible interstitial nephritis.

Statins may cause derangement of liver function tests and should be used with caution in patients with liver disease, but do not cause renal impairment.

16

Regarding maximum urinary concentration

A. Is dependent mainly on the proximal tubular cells
A. The collecting ducts.
B. Is impaired in hyperkalaemia
B. It is impaired in hypercalcaemia (polyuria and polydypsia): hypercalcaemia may cause nephrogenic diabetes insipidus.
C. Is impaired in hypocalcaemia
C. Hypercalcaemia - see above.
D. Is increased in severe malnutrition
D. The maximum concentrating and diluting ability of the kidney is impaired in severe malnutrition.

E. Involves the action of water-permeable channels within cells
E. This is a most bizarre question to ask! It is true and it is the final step in the action of vasopressin (antidiuretic hormone). Vasopressin binds to specific renal tubular receptors which activate cAMP. This leads to activation of intracellular protein kinases to organise microtubules and microfilaments that open water channels across the luminal cell membrane.

17

characteristic feature of severe primary water depletion?

Peripheral circulatory failure
The patient may well display features of shock with hypotension, tachycardia and hypothermia. Mucosal membranes would appear dry.

High serum sodium would be expected, with decreased urine output and increased urine sodium and osmolality.

Osmolality of 300 milliosmol/kg is a relatively dilute urine.