Renal Plasma Clearance Flashcards

(67 cards)

1
Q

What is GFR?

A

how much filtrate is removed from blood each minute

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2
Q

What is the first step of urine formation?

A

1st step in urine formation begins with glomerular filtration

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3
Q

How does GF composition differ from plasma?

A

same composition as plasma except:
Devoid of cellular elements like RBC
Essentially protein-free

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4
Q

What does the presence of protein in urine suggest?

A

Urine routinely tested on wards for protein - proteinuria; sign of renal/urinary tract disease
(>0.5g/day OR ≥250mg/L on test-strip)

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5
Q

How is filtration rate regulated?

A

Filtration across the capillaries is determined by opposing forces (PGC and PBS)

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6
Q

Which force favours filtration?

A

Favouring filtration:

Glomerular capillary pressure (PGC) = 60mmHg

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7
Q

Which force opposes filtration?

A

Hydrostatic pressure in Bowman’s space (PBS) = 15mmHg

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8
Q

What is the osmotic force of plasma proteins?

A

Osmotic force of plasma proteins (ΠGC) = 29mmHg

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9
Q

How do we determine the net filtration pressure?

A

PGC – PBS – ΠGC = 16mmHg (net filtration pressure)

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10
Q

How do we determine the urinary excretion rate?

A

Urinary excretion rate = GFR – reabsorption rate + secretion rate

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11
Q

What factors determine GFR?

A
  • hydrostatic* and oncotic pressures across capillary
    membranes
  • permeability of capillary filtration barrier & surface area
    available
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12
Q

What is the significance of GFR?

A

GFR important clinical indicator of functioning of nephrons (renal function)
contributes to rapid removal of waste products

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13
Q

When do the renal processes (e.g GF, Tubular reabsorption etc.) occur?

A

Each of the processes i.e. GFR, tubular reabsorption and tubular secretion regulated according to needs of the body

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14
Q

Explain how the kidneys respond to excess Na in body

A

excess Na in body:
Na filtering rate increased
Na reabsorption rate is decreased
=> resulting in increased urinary excretion of Na

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15
Q

What is the effect of a high GFR?

A

High GFR allows kidneys to rapidly remove waste products that depend primarily on glomerular filtration for their excretion
Kidney can precisely & rapidly control volume and composition of body fluids

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16
Q

How do we measure GFR?

A

GFR is not measured directly but by measurement of the excretion of a marker substance

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17
Q

Explain how creatinine passes through the kidneys

A
  • Filtration onky

Freely filtered but neither reabsorbed or secreted. Hence it’s excretion rate is = to rate at which filtered

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18
Q

How are electrolytes processed through the kidneys?

A
  • Filtration + Partial Reabsorption
    freely filtered but partly reabsorbed from tubules back into blood. Hence rate of urinary excretion is less than rate of filtration at glomerular capillaries (eg. Many electrolytes in body)
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19
Q

Explain the passage of glucose and amino acids through the kidneys

A
  • Filtration + Complete Reabsorption

Freely filtered but NOT excreted into urine as all filtered substance reabsorbed from tubule back into blood

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20
Q

Explain the fate of organic acids as they pass through the nephrons of the kidneys

A
  • Filtration + Secretion
    Freely filtered but NOT reabsorbed and additional quantities secreted from peritubular capillaries into renal tubules (eg organic acids & bases)
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21
Q

What is the gold standard method for measuring GFR?

A

Inulin method

NOT used clinically

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22
Q

Describe the Inulin method of measuring GFR

A

An inert polysaccharide, MW ~5,000
Filters freely through the glomerular membrane
Not absorbed, secreted or metabolised

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23
Q

How is urine flow rate calculated?

A

V = urine volume collected / collection period

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24
Q

How do we calculate amount of inulin filtered out per min?

A

So the load of inulin filtering from the plasma into BC over 1 min is Pin x GFR

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25
How do we calculate the rate at which inulin enters the bladder?
Rate at which inulin enters the bladder is: | Uin x urine flow(V)
26
What is renal clearance?
The volume of plasma that is completely cleared of the substance by the kidney per unit of time, (ml/min)
27
How can we calculate the clearance rate of a substance?
Cs x Ps = Us x V* ``` Cs = clearance rate of substance (s) Ps = plasma concentration of s Us = urinary concentration of s V* = urine flow rate ```
28
What are the drawbacks of the inulin method?
prolonged infusion repeated plasma samples difficult routine clinical use Clinically use creatinine for GFR measurement
29
What are the advantages of measuring GFR using creatine?
``` Advantages: An intrinsic inert substance Released at ~steady level in plasma from skeletal muscle No infusion needed Freely filtered Not reabsorbed in the tubule ```
30
What are the disadvantages of using creatine?
Some secreted into the tubule
31
What is trimethoprim?
*Trimethoprim (antibiotic) – competitive inhibitor of creatinine
32
What is the role of Trimethoprim?
Trimethoprim competes with Crn for same transporters that secrete Crn from tubular blood into urine » increase in serum levels of Crn
33
Where is creatine found in the body?
Cr (94%) found in muscular tissues.
34
Where is creatine formed?
Muscle virtually has no Cr-synthesizing capacity, so Cr has to be taken up from blood against [large] gradient by Na+ / Cl- dependent transporter
35
What is the rate of creatine clearance?
The serum creatinine concentration is inversely proportional to the creatinine clearance. GFR declines with age
36
What is eGFR?
eGFR is estimated Glomerular Filtration Rate
37
How is eGFR found?
Using blood tests, age, sex, and sometimes other information to estimate the GFR from the MDRD equation*
38
How are the stages of Chronic Kidney Disease (CKD) defined?
The stages of CKD (Chronic Kidney Disease) are mainly based on measured or estimated GFR
39
How many stages are there of CKD?
There are five stages but kidney function is normal in Stage 1, and minimally reduced in Stage 2
40
What factors should be taken into consideration when using eGFR?
- Only an estimate; significant error possible - eGFR most likely inaccurate for extreme body types - Not valid in pregnant women, patients <70yrs or children - Race: Some racial groups don't fit MDRD equation well - was originally validated for US white & black patients.
41
Why does inulin clearance in men and women differ?
Because of the difference in body weight & body surface area between men & women the inulin GFR/clearance is different
42
Which substances are cleared equal to GFR?
Substance with clearance = inulin (= GFR) | e.g. antibiotics (streptomycin/gentomycin)
43
What is the difference in clearance between men and women?
Clearance of Inulin (GFR) ~ 125ml/min in adult male and 10% less in females
44
Which substances are cleared < inulin?
Substance with clearance < inulin (< GFR) Not filtered freely Or reabsorbed from tubule
45
What substances have a clearance > inulin?
Substance has clearance > inulin (>GFR) | Secreted into tubule
46
When might Clearance < GFR?
Not freely filtered E.g. Albumin clearance = 0 ml/min Similarly for drugs bound to albumin e.g. digoxin, warfarin OR Substance that is reabsorbed Filters freely but usually absent from urine ⇒ completely reabsorbed e.g. Glucose clearance = 0 ml/min
47
Describe the rate of glucose filtration
Rate of glucose filtration increases with plasma [glucose] | until a plasma [gluc] of ~15mM is reached (renal threshold - no glucose in the urine)
48
Why is there no glucose present in urine?
PCT has reabsorbed the entire load (via carrier mechanism with Na)
49
What happens if plasma [gluc] exceeds threshold?
Above threshold glucose starts to appear in the urine and then the reabsorption falls short of the filtration
50
What is the Transport maximum?
Rate at which glucose carrier mechanism is fully saturated
51
Why does glucose appear in urine before Transport maximum is reached?
Different nephrons have different Tm so some start excreting glucose in urine before others
52
Describe the rate of glucose clearance at low Pgluc
At low values of Pgluc: | glucose clearance = 0 but above the renal threshold it climbs rapidly at first then more slowly
53
Why does glucose never reach inulin clearance?
some glucose is always reabsorbed by glucose carrier mechanism
54
When may active reabsorption cause clearance of substances < GFR ?
All amino acids clearance = 0 ml.min-1 unless excess filtered pathological conditions (e.g. myeloma) production of Bence-Jones protein in plasma Ca2+, Na+, PO42-, Mg2+ Water-soluble vitamins
55
Which substaces are passively reabsorbed giving clearance < GFR?
Cl–, urea, some imp. drugs
56
Why do some drugs have a clearance < GFR?
As GF flows down tubule & more water is reabsorbed, solutes are concentrated providing conc gradient down which they diffuse But only lipid soluble substances can cross tubular wall, so lipophilic drugs tend to return to blood stream whilst hydrophilic drugs lost in urine
57
What type of substances are secreted into urine by tubular cells?
Filters freely Secreted actively against electrochemical gradient Endogenous substances - e.g. weak organic acids/bases, adrenaline, dopamine, steroids Exogenous substances - e.g. penicillin, probenecid, para-amino hippuric acid (PAH)
58
What is renal plasma flow (RPF?)
RPF is the rate at which plasma flows through the kidney
59
Describe the plasma & composition of blood
Blood consists of about 55% plasma and about 45% cellular components (mostly RBCs)
60
What is PAH?
Weak acid metabolite found in horse urine Filtered freely & enters GF Large amount still in plasma Majority secreted back into PCT ⇒ excreted in urine Suitable as a marker to measure RPF
61
What is the significance of PAH secretion?
> can be given to determine renal blood flow Active transport occurs in basolateral membrane Passive transport across luminal membrane into tubule
62
How does PAH relate to renal plasma flow?
PAH Clearance - RPF | If plasma [PAH] low enough <0.12mg/ml (
63
What is the filtration fraction?
fraction of plasma that is filtered through the glomeruli
64
How can we calculate the filtration fraction?
GFR & RPF can be used to calculate the filtration fraction Filtration Fraction = GFR / RPF = 125 / 660 (x100) =19%
65
How do we determine GFR?
GFR determined from Inulin clearance
66
How do we determine RPF?
RPF determined from PAH clearance
67
What is the clearance of urea?
Urea has a clearance of 65 ml.min-1