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P1: Ren > Renal Clearance > Flashcards

Renal Clearance Flashcards

1
Q

What is GFR?

A

→ How much filtrate is removed from the blood each minute

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2
Q

What is the first step in urine formation?

A

→ Begins with glomerular filtration

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3
Q

What is the composition of glomerular filtrate like?

A

→ same as plasma
→ no cells
→ protein-free

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4
Q

What is proteinuria a sign of?

A

→ renal/ urinary tract disease

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5
Q

What is the primary force favoring filtration?

A

→ Glomerular capillary pressure = 60mmHg

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6
Q

What is the force opposing filtration?

A

→ Hydrostatic pressure in Bowman’s space = 15mmHg

→ Osmotic force of plasma proteins = 29mmHg

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7
Q

What is the urinary excretion rate?

A

→ GFR - reabsorption rate + secretion rate

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8
Q

What does GFR contribute to?

A

→ rapid removal of waste product

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9
Q

How much is the GFR per day?

A

→ 180L per day

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10
Q

How much is the body plasma volume?

A

→ 3L

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11
Q

What 2 factors is GFR determined by?

A

→ hydrostatic and oncotic pressures across capillary membranes
→ permeability of capillary filtration barrier & surface area available

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12
Q

How is GFR measured?

A

→ not directly but by the measurement of the excretion of a marker
→ a substance that is freely filtered but neither reabsorbed or secreted e.g creatinine

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13
Q

What is inulin?

A

→ inert polysaccharide

→ filters freely through the glomerular membrane

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14
Q

When does plasma inulin concentration become stable?

A

→ When inulin fusion rate = inulin excretion rate

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15
Q

What is the GFR equation for the inulin method?

A

→ GFR = Uin x V / Pin
→ V = urine vol/collection time
→ Pin = plasma inulin concentration
→ Uin = urine inulin concentration

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16
Q

What is the definition of renal clearance?

A

→ The volume of plasma that is completely cleared of the substance by the kidney per unit time (excreted in urine each minute)

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17
Q

What is the clearance of inulin?

A

→ same as the GFR
→Since clearance is defined as the volume of plasma ‘cleared’ of a substance in 1 min, the clearance for I is 125 ml/min. This means that of the 625 ml of plasma that come to the kidney in one minute, 125 ml (the fraction that is filtered) has all of the I removed from it in that minute, the other 500 ml (the fraction that is not filtered) keeps its I as there is no way for the I get into the urine as it is not secreted.

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18
Q

What are the drawbacks of the inulin method?

A

→prolonged infusion
→ repeated plasma samples
→ difficult routine clinical use

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19
Q

What is used clinically to measure GFR?

A

→ creatinine

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20
Q

What are the advantages of using creatinine ?

A 
→intrinsic inert substance
→ released at a steady level in plasma from skeletal muscle
→ no infusion needed
→ freely filtered
→ not reabsorbed
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21
Q

What are the disadvantages of creatinine?

A

→ some is secreted into the tubule

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22
Q

What is trimethoprim?

A

→ competitive inhibitor of creatinine
→ given during kidney infections etc
→cause an artificial increase in serum creatinine

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23
Q

How is creatine made?

A

→ Taken in the diet

→ found in the liver

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24
Q

What is creatine metabolized by?

A

→ metabolized to phosphocreatine by the muscle

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25
Q

What can creatine and phosphocreatine be metabolized into?

A

→ creatinine

→ non enzymatic reaction

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26
Q

What does the transporter that transports creatinine also transport?

A

→trimethoprim

→ higher affinity for trimethoprim

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27
Q

If plasma creatinine goes up what happens to the GFR?

A

→ GFR decreases

28
Q

Why are there differences in GFR?

A

→ age
→ gender
→ muscle mass

29
Q

What is eGFR?

A

→ estimated GFR

→ not valid in pregnant women or children, poor inpatients older than 70yrs

30
Q

What factors are taken into account in eGFR?

A

→ age
→ gender
→ ethnicity

31
Q

Why is eGFR a better method?

A

→ much simpler
→ requires one blood test
→ It is being used increasingly to spot kidney disease earlier than would be possible using just creatinine measurements

32
Q

What are the 2 equations used in eGFR?

A

→ MDRD
→ CDK - EPI
→ CKD-EPI is more accurate than MDRD, less biased at GFR ≥60ml/min/1.73m2

33
Q

What are the disadvantages of GFR?

A

→ it is an estimate
→ Inaccurate for people of extremes of body type
→ not valid in pregnant women, over 70 or children
→ Racial groups might not fit the MDRD equation

34
Q

What does it mean if a substance has the same clearance as inulin?

A

→ freely filtered
→ not reabsorbed or secreted
→ ~ 125ml/min in adult male and 10% less in females
e.g. antibiotics (streptomycin/gentomycin)

35
Q

What does it mean if a substance has a clearance less than inulin, GFR?

A

→ not filtered at the top

→ or freely filtered but reabsorbed from tubule

36
Q

What is an example of a substance that is not freely filtered?

A

→ albumin

37
Q

What is an example of a substance that is reabsorbed completely?

A

→ glucose
→Glucose like inulin is freely filtered, so is then present in Bowman’s capsule,
→ no glucose is in urine hence it is completely reabsorbed from tubule and goes back into plasma. →Hence clearance is 0ml/min because as the plasma leaves the kidney (not nephron) it has NO glucose removed.

38
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)

39
Q

What is the equation for calculating glucose filtration?

A

→ GFR x Plasma glucose

40
Q

What is the equation for calculating glucose excretion?

A

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

41
Q

What is the equation for calculating glucose reabsorption?

A

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

42
Q

What is the renal threshold of glucose?

A

→ 15 mM

43
Q

What happens after the plasma glucose level > renal threshold?

A

→ glucose appears in the urine

→ glucose is excreted

44
Q

What happens to the glucose < 20mM?

A

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

45
Q

What happens to the glucose after > 20mM?

A

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

46
Q

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

A

→ Humans have 2 million nephrons
→ Each nephron has a slightly different transport maximum
→ Some nephrons will start excreting glucose earlier than others

47
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

48
Q

What is a substance that is actively reabsorbed?

A

→ Amino acids
→ Ca2+, Na+, PO4 2-, Mg 2+
→ Water soluble vitamins

49
Q

What do actively reabsorbed substances all have?

A

→ a TM

50
Q

What are passively reabsorbed substances?

A

→ Cl-
→urea
→important drugs

51
Q

What are endogenous substances that are secreted?

A

→ Weak organic acids & bases
→ Adrenaline
→ Dopamine
→ Steroids

52
Q

What are exogenous substances that are secreted?

A

→Penicillin
→Probenecid
→ PAH (para amino hippuric acid)

53
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

54
Q

What is RPF?

A

→ Rate at which plasma flows through the kidney- renal plasma flow
→Estimating the RPF through the kidneys allows us to estimate the rate of total blood flow (RBF) through the kidneys

55
Q

What is the composition of the blood?

A

→ 55% plasma

→ 45 % cellular components

56
Q

What is PAH?

A

→ Weak acid metabolite found in horse’s urine

57
Q

What happens to PAH once it enters the glomerulus?

A 
→ Filtered freely + enters the filtrate
→ Large amount is still in plasma
→majority is secreted back into PCT
→Excreted as urine
→So renal clearance rate is higher than GFR- nice tool to measure renal plasma flow
58
Q

How is PAH secreted?

A

→ Active transport occurs in the basolateral membrane

→ Passive transport across the luminal membrane into the tubule

59
Q

What happens if PAH is below the Tm?

A

→ It is cleared in a single pass

60
Q

What is the equation for renal plasma flow?

A

→ (U PAH x V) / Plasma PAH

61
Q

What is the relationship between plasma creatine concentration and clearance rate?

A

Inverse relationship between plasma conc of creatinine and the clearance rate
High creatinine in plasma is low percentage of GFR

A very small increase in plasma creatinine could be cause of a big reduction in kidney function

plot 1/[Cr] to get a linear relationship

62
Q

What is the CKD stages?

A

→ mainly based on measured or estimated GFR.

→ There are five stages but kidney function is normal in Stage 1, and minimally reduced in Stage 2

63
Q

What does it mean for a substance with clearance > inulin?

A

Secreted into tubule

→ Substance with greater clearance than inulin is being added to the fluid as it flows along tubule

64
Q

Why do substances that are passively reabsorbed not display Tm?

A

because their rate of transport is determined by other factors e.g. electrochemical gradient, permeability etc.

65
Q

What is the difference between lipophilic and hydrophilic drugs?

A

lipophilic drugs tend to return to blood stream whilst hydrophilic drugs lost in urine.

P1: Ren (13 decks)

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