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SGUL - Physiology 1 > Renal Plasma Clearance > Flashcards

Renal Plasma Clearance Flashcards

1
Q

List the forces favouring filtration.

A

Glomerular capillary pressure - usually 60 mmHg

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2
Q

List the forces opposing filtration.

A
  • Hydrostatic pressure in the Bowman’s space - usually 15 mmHg
  • Osmotic force of plasma proteins - usually 29 mmHg
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3
Q

Why is the GFR important?

A

Rapid removal of waste products

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4
Q

How are GFR and plasma volume related?

A
  • GFR is around 180 L/day
  • Plasma volume is about 3 L
  • Entire plasma can be filtered around 60 times a day
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5
Q

What factors determine GFR?

A
  • Hydrostatic and oncotic pressures across the capillary membranes
  • Permeability of the capillary filtration barrier
  • Surface area available
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6
Q

Why is GFR important clinically?

A

Indicates renal failure if too low

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7
Q

How do we measure GFR?

A
  • Using a substance that is freely filtered, but neither reabsorbed nor secreted
  • Excretion rate is equal to the rate at which it is filtered
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8
Q

What is the inulin method?

A
  • Inert polysaccharide
  • Filters freely through the glomerular membrane.
  • Not absorbed, secreted or metabolised.
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9
Q

Using the inulin method, what is the equation for measuring GFR?

A

GFR = (Uin x V*)/ Pin

GFR is in ml/min, Pin is plasma inulin concentration in mg/ml, Uin is urine inulin concentration in mg/ml and V* is urine flow rate in ml/min.

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10
Q

What is the definition of renal clearance?

A

Volume of plasma that is completely cleared of the substance by the kidney per unit of time

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11
Q

What is the renal clearance formula?

A

Cs = (Us x V*) / Ps

Cs is the clearance rate of a substance, Ps is the plasma concentration of the substance, Us is the urinary concentration of the substance and V* is the urinary flow rate.

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12
Q

List some drawbacks of the inulin method.

A
  • Prolonged infusion
  • Need repeated plasma samples
  • Difficult routine clinical use
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13
Q

What is an alternative instead of inulin for GFR determination?

A

Creatinine

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14
Q

List some advantages of using the creatinine method for measuring GFR.

A
  • an intrinsic inert substance
  • no infusion needed
  • freely filtered
  • not reabsorbed in the tubule
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15
Q

List some disadvantages of using the creatinine method for measuring GFR.

A
  • some is secreted into the tubule
  • causes higher than expected GFR reading
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16
Q

Describe how trimethoprim affects creatinine serum levels.

A
  • Competes with creatinine for the same transporters that secrete creatinine from the tubular blood into the urine. Greater affinity for trimethoprim
  • Increases the serum levels of creatinine.
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17
Q

Does trimethoprim influence GFR?

A

No

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18
Q

Using the creatinine method, what is the equation for measuring GFR?

A

GFR ≈ Ccr = (Ucr x V*) / Pcr

Ccr ∝ 1/Pcr

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19
Q

How is GFR affected with age?

A

Declines with age

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20
Q

What factors need to be accounted for when determining GFR?

A

Age
Gender
Weight

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21
Q

What is eGFR?

A

estimated Glomerular Filtration Rate

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22
Q

Why is eGFR used?

A

Simple - only uses a single blood test

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23
Q

What are some problems faced when using eGFR?

A
  • Only an estimate -significant error is possible.
  • eGFR is most likely to be inaccurate in people at extremes of the body (eg. malnourished, amputees, etc.).
  • Not valid for pregnant women, patients older than 70 years old or children.
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24
Q

Describe what happens when GFR = 90+, and the treatment.

A
  • Normal kidney function
  • Urine, findings, structural abnormalities or genetic traits point to kidney disease.
    TREATMENT: observation, control of blood pressure.
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25
Q

Describe what happens when GFR = 60-89, and the treatment.

A

Mildly reduced kidney function; this and other findings point to kidney disease.
TREATMENT: observation, control of blood pressure and risk factors.

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26
Q

Describe what happens when GFR = 45-59/ GFR = 30-44 and the treatment.

A

Moderately reduced kidney function.
TREATMENT: observation, control of blood pressure and risk factors.

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27
Q

Describe what happens when GFR = 15-29 and the treatment.

A

Severely reduced kidney function.
TREATMENT: planning for end-stage renal failure.

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28
Q

Describe what happens when GFR<15/on dialysis, and the treatment.

A

Severe or end-stage kidney failure
TREATMENT: treatment choices.

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29
Q

Compare clearance to inulin.

A

By comparing the clearance of a substance to inulin (and in effect, GFR) tell a lot about the renal handling of that substance.

30
Q

What is the identity of a substance with clearance=inulin?

A

Antibiotics e.g streptomycin

31
Q

What happens to a substance with clearance < inulin?

A

Not filtered freely, or reabsorbed from the tubule

32
Q

What happens to a substance with clearance > inulin?

A

Secreted into the tubule.

33
Q

What does it tell you about a substance when the clearance < GFR? PART 1

A

Substance is not freely filtered:
- Albumin clearance is 0 ml/min. This is similar to drugs bound to albumins, such as digoxin and warfarin.

34
Q

What does it tell you about a substance when the clearance < GFR? PART 2

A

Substance is reabsorbed.:
- Filters freely but usually absent from the urine as it is completely reabsorbed. For example, the glucose clearance is also 0 ml/min.

35
Q

Describe the glucose handling of the kidney.

A

15 mM is the renal threshold.
- Above this threshold, glucose starts to appear in the urine, and then the reabsorption line falls short of the filtration line.

36
Q

What occurs when reabsorption line plateaus?

A
  • Plateaus at 22 mM.
  • Transport Maximum (Tm) for glucose ie. the rate at which the carrier mechanism is fully saturated.
37
Q

List some substances that are actively reabsorbed.

A
  • amino acids
  • Ca2+, Na+, PO4 2-, Mg2+
  • water-soluble vitamins
38
Q

List some substances that are passively reabsorbed.

A

Cl-
urea
some important drugs

39
Q

What is the main difference between actively reabsorbed and passively reabsorbed substances?

A

Substances that are passively reabsorbed DON’T display Tm.

40
Q

Why do passively reabsorbed substances not display Tm?

A

Rate of transport is determined by the other factors (eg. electrochemical gradient, permeability, etc.).

41
Q

How does glomerular filtrate help form a concentration gradient for solutes?

A
  • Glomerular filtrate flows down the tubule
  • Water is reabsorbed
  • Solutes are concentrated, providing a concentration gradient down which they diffuse.
42
Q

What type of substances can diffuse across the tubule wall?

A

Lipid-soluble substances

43
Q

What is the importance of only lipid-soluble substances being able to diffuse across the tubule wall?

A
  • Lipophilic drugs tend to return to the bloodstream
  • Hydrophilic drugs are lost in the urine.
44
Q

What can we tell about a substance that has its clearance > GFR?

A

We can tell that it is a substance that is secreted.
- it filters freely
- it is secreted actively against the electrochemical gradient

45
Q

Give example of endogenous substances.

A
  • Weak organic acids and bases
  • Adrenaline
  • Dopamine
  • Steroids
46
Q

Give examples of exogenous substances.

A
  • Penicillin
  • Para-amino hippuric acid (PAH)
47
Q

Describe RPF (renal plasma flow)

A
  • Rate at which plasma flows through the kidney.
48
Q

Describe RBF (renal blood flow)

A

Blood consists of about 55% plasma and about 45% cellular components (mostly RBCs).

49
Q

What does an estimation of RPF allow?

A

Allows to estimate the rate of total blood flow through the kidneys.

50
Q

Describe PAH (para-aminohippurate acid).

A
  • Weak acid metabolite
  • Filtered freely and enters the glomerular filtrate.
  • Large amount in the plasma.
51
Q

What makes PAH suitable to measure renal plasma flow?

A

Majority of it is secreted back into the proximal convoluted tubule and excreted into the urine.

52
Q

With PAH secretion, describe the different transport mechanisms across the different membranes.

A
  • Active transport occurs in the basolateral membrane.
  • Passive transport occurs across the luminal membrane into the tubule.
53
Q

With PAH, what is the equation for RPF?

A

Amount of PAH delivered to the kidneys in the blood is equal to the amount excreted in the urine. So:

RPF = (Upah x V*) / [PAH]

54
Q

How do we calculate the renal filtration fraction?

A

Filtration Fraction = GFR/RPF
GFR is determined from inulin clearance, while RPF is determined from PAH clearance.

55
Q

What happens if PAH is below the Tm?

A

→ It is cleared in a single pass

56
Q

Why does the concentration of penicillin fall rapidly when injected and how is this counteracted?

A

→ Renal tubular cells actively secrete it into the urine
→ Given with probenecid which competes for the same transport mechanism

57
Q

Why does the clearance rate of glucose never reach the rate of inulin?

A

→ the transporters are still working unless they are completely blocked

58
Q

Why does glucose start appearing in the urine before 20mM?

A

→ Each nephron has a slightly different transport maximum
→ Some nephrons will start excreting glucose earlier than others

59
Q

What happens to the glucose after > 20mM?

A

→ All the transporters are saturated
→ Glucose reabsorption plateaus
→ Glycosuria

60
Q

What happens to the glucose < 20mM?

A

→ All the glucose that filters through is reabsorbed by the Na+/glucose co-transporter

61
Q

What is the equation for calculating glucose reabsorption?

A

→ [(GFR x Pglucose) - ( U glucose x V)]

62
Q

What is the equation for calculating glucose excretion?

A

→ Uglucose (urine glucose concentration) x V (urine flow rate)

63
Q

What is the equation for calculating glucose filtration?

A

→ GFR x Plasma glucose

64
Q

How is glucose handling by the kidney investigated?

A

→ infuse glucose and inulin together
→ calculate GFR using inulin
→ calculate the glucose filtration rate (GFR x plasma glucose concentration)

65
Q

Why are there differences in GFR?

A

→ age
→ gender
→ muscle mass

66
Q

How is creatine made?

A

→ Taken in the diet
→ found in the liver

67
Q

What is creatine metabolized by?

A

Phosphocreatine

68
Q

What can creatine and phosphocreatine be metabolized into?

A

Creatinine

69
Q

What is the urinary excretion rate?

A

GFR - reabsorption rate + secretion rate

70
Q

What is proteinuria a sign of?

A

Renal/ urinary tract disease

SGUL - Physiology 1 (68 decks)

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