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Physiology 1 Semester 2 > Renal Plasma Clearance > Flashcards

Renal Plasma Clearance Flashcards

1
Q

What substance is goof to use for GFR?

A

A substance that is only filtered and is not partially or almost completely reabsorbed - all of what is put in will be filtered out

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2
Q

Describe why inulin can be used to find GFR including what is it and how it passes through the kidney

A
  • An inert polysaccharide that has a molecular weight of 5000
  • Filters freely through the glomerular membrane
  • Not absorbed - secreted or metabolised
  • When inulin is added there will be a [plasma inulin]
  • Some of this will continue in the bloodstream but some will pass through the glomerulus and into the tubule
  • It is not reabsorbed or secreted so there will be a [urine inulin]
  • Hence the rate of filtration through the glomerular membrane = the rate of entry into the bladder
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3
Q

State how to find the rate of inulin filtration and the units for the components of the equation

A

The rate of inulin filtration = [plasma inulin] x GFR

  • [plasma inulin] has the units mg/ml
  • GFR has units mg/min
  • Hence rate of inulin filtration has the units mg/min
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4
Q

State how to find the rate of entry into the bladder

A

The rate of entry into the bladder = [urine inulin] x urine flow rate (the urine volume collected/time)

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5
Q

[plasma inulin] x GFR is equal to?

A

= [urine inulin] x urine flow rate

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6
Q

How do you calculate GFR

A

GFR (ml/min) = [urine inulin (mg/ml)] x urine flow rate (ml/min) / [plasma inulin (mg/ml)]

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7
Q

What is renal clearance

A

Renal clearance of a substance is the volume of plasma that is completely cleared (excreted into urine) of the substance by the kidney per unit of time (ml/min)

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8
Q

Describe how we would calculate the renal clearance of insulin

A
  • The plasma enters the afferent arteriole at a rate of 625 ml/min
  • As the rate of flow through the glomerulus is 1/5th the rate it flows through the glomerulus at 125 ml/min
  • Inulin is not reabsorbed or secreted so all filtered inulin ends up in the urine
  • The clearance is the volume of plasma cleared of the substance in one minute which would be 125ml/min = GFR
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9
Q

How do you find the clearance rate of substance S

A

(urinary concentration of s x urine flow rate) / plasma concentration of S

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10
Q

What are the drawbacks of using insulin

A
  • Requires prolonged infusion
  • Needs to have repeated plasma samples
  • It is difficult to use as a routine clinical procedure
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11
Q

What are the advantages and disadvantages of using creatinine

A
  • Advantages of using creatinine -
  • It is an intrinsic inert substance
  • Released at a steady level in the plasma from skeletal muscle
  • No infusion is needed
  • Freely filtered
  • Not reabsorbed in the tubule
  • Disadvantages of using creatinine -
  • Some is secreted into the tubule
  • GFR is less than the renal clearance rate - has a typical rate of 150ml/min rather than 125ml/min
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12
Q

Describe where creatinine is formed

A
  • Comes from the diet or the liver where it enters the muscles
  • It is then metabolised in the muscle into phosphocreatine by creatine kinase and creatine and phosphocreatine then form creatinine
  • Creatinine is a waste product that is then excreted in the urine
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13
Q

Why do antibiotics create higher creatinine levels?

A
  • When creatinine is secreted it is by an active mechanism that is by the same transporter than is inhibited by an antibiotic called trimethoprim
  • Those on trimethoprim have higher plasma creatinine levels
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14
Q

Relate GFR to renal clearance rate via an equation

A

GFR = renal clearance rate = [urine creatinine] x urine flow rate / [plasma creatinine]

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15
Q

Show that there is an inverse relationship between plasma clearance rate and plasma creatinine

A

Plasma clearance rate is proportional to 1/ [plasma creatinine]

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16
Q

Describe what [creatinine] and 1/[creatinine] look like on a graph against GFR

A
  • When [creatinine] is high the % of normal GFR is low (curve downwards)
  • When 1/[creatinine] is low the % of normal GFR is low and increases as 1/[creatinine] increases (straight line )
  • GFR does decrease naturally with age so this fact must be considered
17
Q

Describe how GFR can be estimated eGFR, its advantages and disadvantages

A
  • Uses an equation using blood tests, age, sex and other information as an estimation
  • Current equation is CKD-EPI adults
    It isn’t as good as urine urine samples but is simpler as it needs just 1 blood test
  • You can spot kidney disease earlier than would be possible only using creatinine to measure
  • K= 0.7 for female and 0.9 for male, alpha = -0.329 for females and -0.411 for males
  • Weight is not needed as results are normalised to 1.73m squared body surface area
  • The test is such that any value above 60ml/min is stated as such and is not given a particular value - the test acknowledges that it is not good above this value
18
Q

Describe the stages of kidney disease (what the GFR is, the function of the kidney and the treatment)

A
  1. 90+ - normal kidney function but urine findings or structural abnormalities or genetic traits point to kidney disease - mildly reduced kidney function and other findings point to kidney disease - treatment with observation, control of blood pressure
  2. 60-89 - mildly reduced kidney function and other findings point to kidney disease - treatment is observation and control of blood pressure and risk factors
  3. A (45-59) B (30-44) - moderately reduced kidney function - treatment is observation, control of blood pressure and risk factors
  4. 15-29 - severely reduced kidney function - planning for end stage renal failure
    Less than 15 or on dialysis- very severe or end stage kidney failure - treatment choices
19
Q

Why is there a significant error in the GFR measurement?

A

significant error is possible- likely to be inaccurate in people with extreme body types e.g. malnourished, amputees etc and isn’t valid in pregnant women, children or impatiens older than 70 years

20
Q

State the 3 relationships between clearance and GFR and how the kidney processes these

A
  1. Substances with clearance = inulin = GFR - 125ml/min in adult males and 10% less in females- e.g. antibiotics
  2. Substances with clearance < inulin (<GFR) - either not filtered freely or reabsorbed from tubule
  3. Substances with clearance > inulin (>GFR) - secreted into tubule
21
Q

State the 2 types of substances that have a clearance > GFR

A
  1. Not freely filtered e.g. albumin clearance = 0ml/min - similarly are drugs bound to albumin e.g. digoxin and warfarin
  2. Substances that are reabsorbed - filters freely but is usually absent from urine - completely reabsorbed - e.g. glucose clearance = 0ml/min
22
Q

How is glucose handled by the kidney? - talk about filtration, excretion and reabsorption

A
  • As [plasma glucose] increases the glucose filtration rate increases (GFR x [plasma glucose])
  • As [plasma glucose] increases the rate of excretion increases ([urine glucose] x urine flow rate) - does not start from 0 starts from the renal threshold of around 10mM
  • As [plasma glucose] increases the reabsorption rate stays constant { (GFR x [plasma glucose]) - ([urine glucose] x urine flow rate) }- this increases till it reaches the transport maximum at which point it will stay constant
23
Q

Describe glucose clearance on a graph

A
  • On a graph of [plasma] (x axis) against clearance (y axis) glucose starts to increase at the glucose renal threshold and then plateaus
  • It plateaus at the point at which GFR - transport maximum (the maximum it could be without reabsorption - the reabsorption)
24
Q

What are some other substances where clearance < GFR?

A
  • Actively reabsorbed -
  • All amino acids - clearance is 0 ml/min unless excess is filtered - pathological conditions e.g. myeloma
  • Ca2+, Na+, PO4 2- and Mg2+
  • Water soluble vitamins
  • Passively reabsorbed -
  • Cl-
  • Urea
  • Some drugs
25
Q

Describe what type of substances have a clearance > GFR and give some examples

A
  • Substances that are secreted
  • Filter freely but also secreted against the electrochemical gradient

Endogenous - weak organic acids and bases, adrenaline, dopamine, steroids
Exogenous - penicillin, probenecid, para aminohippuric acid

26
Q

Define renal plasma flow

A

The rate at which plasma flows through the kidney

27
Q

What does estimating renal plasma flow allow us to estimate?

A

Allows us to estimate the rate of total blood flow through the kidneys as blood contains 55% plasma and 45% cellular components

28
Q

Describe what paraaminohippuric acid is and why it can be used as a marker for renal plasma flow

A
  • This is a weak metabolite of glycine originally found in horses urine
  • Filtered freely and enters glomerular filtrate but there is a large amount still in the plasma (4/5ths)
  • Majority is secreted back into proximal convoluted tubule - excreted in the urine
  • Hence it is a suitable marker to measure renal plasma flow
29
Q

How is PAH secreted

A
  • Between the epithelial cells of the tubule and the blood capillary there is a Na+/K+ ATPase that pumps 3Na+ ions into the capillary and 2K+ ions into the epithelial cells
  • This creates a Na+ gradient so Na+ enters epithelium via a cotransporter than also transports PAH into the epithelial cells
  • PAH then passes into the lumen of the tubule via passive movement through a cotransporter that transporters anions into the epithelial cells
30
Q

Describe PAHs renal plasma flow

A
  • If plasma (PAH) is low enough it is virtually completely cleared in a single pass through the kidney
  • Hence the rate at which PAH enters the kidney = the rate at which PAH leaves the kidney in the urine
  • Rate of PAH entering kidney = RPF x [plasma PAH]
  • Rate of PAH leaving kidney = [urine PAH] x urine flow rate

Hence = RPF = ( [urine PAH] x urine flow rate ) / [plasma PAH]

31
Q

Describe what filtration fraction is and what is needed to calculate it

A

Renal filtration fraction -
- GFR and RPf can be used to calculate the filtration fraction
- I.e. the fraction of plasma that is filtered through the glomeruli

Filtration fraction = GFR (the rate at which it is filtered through the glomeruli) / RPF (rate at which all plasma is passing through the kidneys)
- GFR is determined from inulin clearance
- RPF is determined from PAH clearance

Physiology 1 Semester 2 (50 decks)

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