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Physiology 1 > 44) Renal Clearance > Flashcards

44) Renal Clearance Flashcards

1
Q

What is inulin?

A
  • An inert polysaccharide which is synthetically made (not made naturally)
  • It is freely filtered through the glomerular membrane and is not absorbed, secreted or metabolised
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2
Q

How is inulin used to measure GFR?

A
  • A known concentration of inulin is injected into a person.
  • Some of this inulin is absorbed by the glomerulus while the rest stays in the blood
  • This inulin that is absorbed by the glomerulus will be expelled in the urine and the concentration of this inulin can be measured
  • Hence any inulin that has been absorbed by the glomerulus will be passed in the urine as none of it will be reabsorbed or secreted
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3
Q

What is the equation for the rate of inulin filtration?

A
  • Rate of inulin filtration = [plasma inulin] x GFR
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4
Q

What is the equation for Rate of entry into bladder?

A
  • Rate of entry into bladder = [urine inulin] x urine flow rate
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5
Q

How does rate of inulin filtration relate to rate of entry into bladder?

A
  • Rate of inulin filtration = rate of entry into bladder

- This means that any inulin filtrated (in the glomerulus) ends in the bladder/urine

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6
Q

What is the overall equation for GFR?

A
  • GFR = ( [urine inulin] x urine flow) / [plasma inulin]
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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 (expressed in ml/min)
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8
Q

How is inulin used to measure clearance?

A
  • Inulin is injected in the plasma where it flows to the kidneys
  • In the kidneys some of it is absorbed by the glomerulus and is unable to pass back into the blood stream
  • Inulin is unable to be absorbed from any other sites other than the glomerulus
  • The filtered/absorbed inulin ends up in the urine
  • Clearance will be the volume of plasma that is cleared off inulin in a minute
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9
Q

What is the equation for clearance rate?

A
  • Clearance rate of a substance = ( [substance in urine] x Urine flow rate) / [substance in plasma]

(Same as equation for GFR)
However clearance is not always the same as GFR

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10
Q

What are the disadvantages of inulin?

A
  • It requires prolonged infusion
  • It requires repeated plasma samples
  • It is very difficult to use in a clinical routine environment
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11
Q

What substance is ideal for clinical GFR measurment?

A
  • Creatinine
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12
Q

What are the advantages of using creatinine to measure GFR?

A
  • It is an inert substance that is already in the blood
  • It is released at a steady state from skeletal muscle into plasma
  • There is no infusion needed
  • It is freely filtered
  • It is not reabsorbed in the tubule
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13
Q

What are the disadvantages of creatinine?

A
  • Some secretion of creatinine from the blood vessels into the tubule
  • Hence the clearance rate is slightly higher than the GFR
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14
Q

How does creatinine end in the urine?

A
  • Creatine (from the diet or from the liver) is taken into the muscle where it is metabolised into creatinine
  • Creatine can also be phosphorylated to phosphocreatine which is metabolised into creatinine
  • This creatinine is a waste product that is released in the plasma which is excreted in the urine
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15
Q

How is creatinine transport affected by other substances?

A
  • Creatinine can be actively transported into the tubules from the plasma
  • Its active transport mechanism can be targetted/inhibited by Trimethoprim (an antibiotic)
  • Patients who take trimethoprim are unable to release creatinine through the secretion pathway and so suffer from an elevated level of plasma creatinine
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16
Q

How can GFR be calculated using creatinine concentration?

A
  • Using the GFR equation we can deduce that Creatinine clearance is inversely proportional to [plasma creatinine]
  • Hence as [plasma creatinine] increases clearance decreases
  • By plotting 1/[plasma creatinine] against GFR we can get a straight line which can be used to get clearance
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17
Q

What affects GFR?

A
  • Age

- Gender

18
Q

What are Estimated Glomerular Filtration Rates (EGFR)?

A
  • An equation that uses blood tests, age, sex and other information to estimate GFR
  • Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) is the standard equation used to estimate GFR in adults
19
Q

What are the disadvantages of EGFR?

A
  • It is not as accurate as measuring the GFR
  • It is an estimate so errors are possible
  • It is most likely to be inaccurate in people with extreme body types
  • It is not valid in pregnant woman or children and is poor in patients older than 70 yrs
20
Q

What are the advantages of EGFR?

A
  • It is much simpler as it requires just one blood sample
  • They can spot kidney disease earlier compared to using creatinine measurements
  • The equation does not require weight
  • There is less bias as it tells people with values greater than 60 to combine their results with observations
  • It works better than some of the other equations
21
Q

How is CKD linked to GFR?

A
  • The stages of Chronic Kidney Disease (CKD) are based on measured/estimated GFR
  • There are five stages but kidney function is normal in stage 1 and minimally reduced in stage 2
22
Q

What are the three different categories of substances in the plasma?

A
  • Substances with clearance = GFR : e.g. antibiotics
  • Substances with clearance < GFR : They are either not filtered freely or reabsorbed by the tubule
  • Substances with clearance > GFR: Occurs when they are secreted into tubules
23
Q

Why do some substances have a clearance < GFR?

A
  • Not freely filtered: (e.g. large proteins such as albumin) Hence they do not pass into the glomerulus and so remain in the blood stream
  • Can be reabsorbed: (e.g. glucose) These substances are filtered freely but are completely reabsorbed back into the blood stream so are absent from the urine
24
Q

What is the glucose renal threshold?

A
  • It is the [plasma glucose] where we experience glucose in the urine
  • Increasing [plasma glucose] causes increased clearance of glucose
25
Q

What is the glucose transport maximum?

A
  • The point at which all the glucose transporters in the kidney are working at their maximum
  • Increasing the glucose past this point has no effect on the rate of reabsorption
26
Q

How does filtration and excretion change with [plasma glucose]?

A
  • As [plasma glucose] increases filtration and excretion also increases
27
Q

At what point does glucose clearance plateau?

A
  • Glucose clearance never exceeds GFR as it only enters the tubules at filtration
  • It plateaus at the point which is equal to GFR -Transport maxima
28
Q

What substances are actively reabsorbed in the kidneys?

A
  • All amino acids
  • Ca2+, Na+, PO42-, Mg2+
  • Water-soluble vitamins

(Each substance has a transport maximum)

29
Q

What substances are passively reabsorbed?

A
  • Cl-
  • Urea
  • Some drugs (lipophilic drugs)

(Their ability to be reabsorbed depends on their electrochemical gradient)

30
Q

Why do some substances have a clearance > GFR?

A
  • These are substances that are secreted from the peritubular capillaries into the tubules
  • They filter freely and are secreted actively against electrochemical gradient
  • They can be endogenous/produced in humans (e.g. weak organic bases and acids, adrenaline, dopamine, steroids) or exogenous (e.g. penicillin, probenecid and para-aminohippuric acid (PAH))
31
Q

What is Renal Plasma Flow (RPF)?

A
  • The rate at which plasma flows through the kidney
  • Estimating the RPF through the kidney allows us to estimate the Rate of total Blood Flow (RBF) through the kidneys
  • Blood consists mainly of plasma with a smaller component being cellular (mostly RBCs)
32
Q

What is Para-Aminohippuric acid (PAH)?

A
  • It is a weak acid which is a metabolite of glycine which was originally found in horse’s urine
  • It is inert and harmless in human urine
33
Q

How is PAH transported in the kidneys?

A
  • It is filtered freely across the glomerulus and so can enter the glomerular filtrate however a large amount remains in the plasma
  • There is also a high level of secretion of PAH into the proximal convoluted tubule via the peritubular capillary
  • This happens as the PAH in the blood is transported into the epithelial cell of the proximal convoluted tubule through an active transporter via a symporter (which also carries Na+).
  • It then crosses into the lumen of the tubule from the epithelial cell along its electrochemical gradient via an antiporter (which carries anions into the epithelial cell)
  • This PAH in the lumen will then be excreted in the urine
34
Q

Why can PAH be used to measure renal plasma flow?

A
  • PAH is a suitable marker to measure renal plasma flow as when [plasma PAH] is low enough all the PAH is cleared in a single pass through the kidneys
  • This is because the transport maximum is a lot higher than the concentration of PAH in the plasma
  • As a result the rate at which PAH enters the kidney in the blood is the same as the rate at which PAH leaves the kidney in the urine
35
Q

What is the equation for rate of PAH entering the kidney in blood?

A
  • rate of PAH entering the kidney in blood = renal plasma flow rate x [PAH in plasma]
36
Q

What is the equation for rate of PAH leaving the kidney in the urine?

A
  • rate of PAH leaving the kidney in the urine = [PAH in urine] x rate at which urine is produced
37
Q

What is the equation for Renal Plasma Flow?

A
  • RPF = ( [PAH in urine] x rate of urine formation) / [PAH in plasma]
38
Q

What is the relationship between PAH clearance and renal plasma flow?

A
  • PAH clearance = renal plasma flow
39
Q

What is the renal filtration fraction?

A
  • The fraction of plasma that is filtered through the glomeruli
40
Q

What is the equation for filtration fraction?

A
  • Filtration Fraction = GFR / Rate of Plasma Flow
  • GFR is determined from inulin clearance
  • Rate of Plasma Flow is determined from PAH clearance

Physiology 1 (64 decks)

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