Biochemistry Flashcards

1
Q

What two functions of the kidneys are assessed using biochemical measurements in renal disease?

A
  • Glomerular function

- Tubular function

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2
Q

What do…
- Glomerular function
- Tubular function
… actually mean?

A
  • Glomerular function: the ability of the glomeruli to filter the blood
  • Tubular function: the ability of the renal tubules to reabsorb the filtered blood from the glomeruli
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3
Q

Glomerular function can be assessed by investigating which two factors?

A
  • Glomerular filtration rate (GFR)

- Proteinuria

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4
Q

What is the single best test for assessing kidney function?

A

GFR

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5
Q

Describe some properties that the ‘ideal marker’ for assessing glomerular filtration rate (GFR) would have

A
  • Endogenous (produced by the body)
  • Easy to measure (e.g., in urine)
  • Appears at a constant rate
  • Freely filtered at the glomerulus
  • Not reabsorbed from the renal tubule
  • Not secreted into the renal tubule
  • Doesn’t undergo extra-renal elimination
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6
Q

Name the plant carbohydrate which gives an almost perfect indication of GFR

A

Inulin

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7
Q

Why is measuring inulin clearance not gold standard for assessing GFR?

A

Inulin is not endogenous - it needs to be injected into the body before being measured which makes it impractical

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8
Q

Clearance of which two substances can be used as a marker for GFR instead of inulin?

A

Creatinine (main one)

Urea

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9
Q

What is urea?

A

The final breakdown product of amino acids found in proteins and the main component of urine

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10
Q

What properties make urea a…
-Good
-Bad
… marker for assessing GFR?

A

Good:

  • Endogenous
  • Easy to measure
  • Freely filtered by the glomerulus
  • Not secreted into the renal tubule

Bad:

  • Levels fluctuate post-prandially (not present at a constant rate)
  • Reabsorbed from the renal tubules
  • Extra-renal elimination by the gut so GFR will be underestimated
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11
Q

What is the most significant limitation for use of urea as a marker of GFR?

A

It’s extra-renal elimination by the gut (~25% of total urea)

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12
Q

What is creatinine?

A

A waste product of muscle metabolism

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13
Q

What properties make creatinine a good marker for assessing GFR?

A
  • Endogenous
  • Easy to measure
  • Appears at a constant rate
  • Freely filtered by the glomerulus
  • Not reabsorbed from the renal tubule
  • Doesn’t undergo extra-renal elimination
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14
Q

What is the limitation of using creatinine as a marker of GFR?

A

~5-10% of creatinine is secreted into the renal tubule so GFR is overestimated

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15
Q

What is the problem with measuring serum creatinine and what is the solution?

A

Problem: serum creatinine isn’t sensitive to changes in GFR until the GFR is significantly lowered (i.e., serum creatinine stays within the reference interval even when GFR has nearly halved)

Solution: urine creatinine clearance is sensitive to changes in GFR at these higher GFR levels (60-120 mL/min)

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16
Q

What is urinary creatinine clearance?

A

The volume of blood that’s cleared of creatinine per minute by glomerular filtration

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17
Q

What 3 measurements are required to calculate urinary creatinine clearance?

A

Serum creatinine
24-hour urine collection creatinine
Urine volume

18
Q

What equation is used to calculate urinary creatinine clearance?

A

(urine creatinine conc. x urine volume) / (serum creatinine conc. x duration of collection*)

  • duration of collection in minutes so 24 hours = 1440 mins
19
Q

Calculate the urinary creatinine clearance:

  • Serum creatinine: 100 micromols
  • Urine creatinine: 6800 micromols
  • Urine volume: 2500 ml
A

(6800 x 2500) / (100 x 1440) = 118 ml/min

20
Q

Serum creatinine is affected by the amount of creatinine produced per day. With this in mind, what are the confounding variables in serum creatinine measurement?

A

Muscle mass and diet

21
Q

Muscle mass and diet cannot reasonably be measured for each patient. What ‘proxies’ are used to take into account the confounding variables?

A

Age, sex and ethnicity

22
Q

Due to the presence of confounding variables and the use of proxies, what are the results of these methods of calculating GFR called?

A

Estimated glomerular filtration rate (eGFR)

23
Q

Clearance of what substance may be used instead of creatinine to get a more accurate eGFR (e.g., in oncology)?

A

51Cr-EDTA clearance

24
Q

Chronic kidney disease is classified from stage 1-5 based on eGFR. What values of eGFR are the range for each stage of CKF?

A

Stage 1: >90 mL/min (may not = KD)
Stage 2: 60-89 mL/min (very mild renal dysfunction)
Stage 3: 30-59 mL/min (decline in renal function, can be due to normal aging)
Stage 4: 15-29 mL/min (needs renal replacement)
Stage 5: <15 mL/min (end-stage renal failure)

25
Q

Why is a eGFR of >=60 mL/min just reported as ‘>=60 mL/min’?

A

eGFR is still not accurate at higher GFR values

So only values <60 mL/min are reported

26
Q

What aspects of glomerular function does measuring proteinuria specifically investigate?

A

The ability of the glomerulus to act as a filter

27
Q

How is proteinuria estimated?

A

By measuring plasma protein content in a 24-hour collection of urine

28
Q

Why does plasma protein content in urine give an indication of glomerular function?

A

Plasma proteins are normally retained by the glomeruli because they are large molecules

‘Leaky’, damaged glomeruli will filter through more plasma proteins than they should

29
Q

What conc. of protein in the urine suggests significant glomerular damage?

A

> 150 mg/day

30
Q

Urine dilution will also affect the protein content of the urine. How is this taken into account?

A

By working out the protein/creatinine ratio in a spot sample of urine

31
Q

Suggest two conditions which can cause proteinuria

A

Multiple myeloma can cause overflow proteinuria (overproduction of Ig’s leak into the urine)

Nephrotic syndrome can cause glomerular proteinuria (the glomeruli are unable to retain protein and so excess protein spills into the urine)

32
Q

What is meant by the term ‘microalbuminuria’?

A

Excretion of albumin in abnormal quantities but still not enough to be detected by a urine dipstick

33
Q

Why is it important to assess for microalbuminuria in patients with diabetes?

A

Microalbuminuria is the earliest expression of diabetic nephropathy

This can be detected and treated early (w/ an ACEI)

34
Q

What is the function of the renal tubules?

A

To reabsorb important substances from the filtrate from the glomeruli e.g., water, electrolytes, amino acids, glucose etc

35
Q

What % of filtrate is reabsorbed?

A

~99%

36
Q

Tubular pathology can be classified as pre-renal, renal or post-renal

Suggest a cause of pre-renal tubular pathology

A

Blood loss/hypovolaemia (reduced renal perfusion)

37
Q

Tubular pathology can be classified as pre-renal, renal or post-renal

Suggest a cause of renal tubular pathology

A

Glomerulonephritis, nephrotoxins (intrinsic kidney tissue damage)

38
Q

Tubular pathology can be classified as pre-renal, renal or post-renal

Suggest a cause of post-renal tubular pathology

A

Stones/malignancy (ureteric/urethral obstruction)

39
Q

What 2 measurements can be used to assess tubular function?

A

Urine osmolality

Serum osmolality

40
Q

How are urine and serum osmolalities used to assess tubular function?

A

Comparing serum and urine osmolalities can help assess tubular function

If the renal tubules are functioning, the values should be different
If the renal tubules are damaged, serum and urine osmolalities will be almost identical as there will be little altering of the filtrate

41
Q

Urine osmolality is most useful if it is either exactly the same as, or very different from serum osmolality. T/F

A

True