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Phys II Unit 1 > L3 and L4 Measuring GFR And Renal Clearance > Flashcards

L3 and L4 Measuring GFR And Renal Clearance Flashcards

1
Q

GFR gives a rough measure of the number of …

A

Functioning nephrons

Decreased GFR is a key sign of renal disease

A reduction in GFR may indicate a disease progression, or development of a reversible problem

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2
Q

Grading of chronic renal insufficiency and dosages of drugs secreted by kidneys are based on…

A

GFR (glomerular filtration rate)

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3
Q

Experimentally, the polysaccharide ______ is often used to measure GFR

A

Inulin

Inulin clearance = GFR

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4
Q

If a material is neither reabsorbed or secreted by the nephron, then…

A

What goes in must come out

GFR = (Ux)(V)/Px

Where:
Ux = concentration of x in the urine
V = Urine rate
Px = concentration of x in the plasma

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5
Q

The perfect marker for GFR is freely filtered but neither _________ nor _________

A

Neither reabsorbed nor secreted

Inulin clearance is the gold standard but it is not commonly used clinically

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6
Q

_____________ clearance and plasma _____________ concentration are frequently used as indicators of GFR in clinical practice

A

Creatinine

Other techniques: EDTA, iothalamate clearance

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7
Q

Creatinine is produced by ____________ at a relatively constant rate from breakdown of ___________________.

A

Skeletal muscle, creatine phosphate

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8
Q

Why use creatinine to measure GFR?

A

It is freely filtered, not reabsorbed, and is only slightly secreted

It is also already at a steady-state concentration in the blood, if formation and excretion are stable

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9
Q

Blood creatinine levels can provide an estimate of …

A

GFR over the preceding hours

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10
Q

Calculation of GFR by determining creatinine clearance can be described by the following formula:

A

Ccr = (Ucr)(V)/Pcr ≈ GFR

Where:
Ccr = Creatinine clearance
Ucr = concentration of creatinine in urine (mg/100ml)
V = volume of urine (ml/min)
Pcr = concentration of creatinine in plasma (mg/100ml)

Normal Ccr ≈ 80-110 ml/min/1.73m2

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11
Q

Method for sample collection in order to properly measure GFR

A

Patient voids on arising at 7 am, urine discarded

Urine collected for 24 hours, including specimen on arising on the following morning at 7 am

Blood same also taken during the same 24 hour period

Ccr = (U x V) / P
Where U = concentration of Cr in urine
V = volume of urine
P = Concentration of Cr in plasma

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12
Q

If a patient’s
Urine flow (V) = 2.0 ml/min
Urine [Cr] = 0.6 mg/ml
Plasma [Cr] = 0.01 mg/ml

What is the patient’s GFR?

A

GFR = (U x V)/P = (0.6 x 2.0)/(0.01) = 120 ml/min

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13
Q

What if all you have is the plasma [Cr]?

A

You can estimate GFR based upon their inverse relationship.

Several algorithms exist for estimating GFR based on plasma creatinine, based on large data sets

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14
Q

The different algorithms used to estimate GFR based on plasma creatinine

A

Cockcroft-Gault equation
- requires age, weight, sex and Pcr

MDRD 4 (Modification of Diet in Renal Disease)
- requires age, sex, race, and Pcr

Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
- requires age, sex, race, and Pcr

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15
Q

What is Blood Urea Nitrogen (BUN)

A

Amino acid catabolism in the liver produces urea —> urea synthesis varies with protein intake and liver function —> about 1/2 of the filtered urea is reabsorbed (reabsorption increases when GFR is low)

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16
Q

________ is not a good GFR marker

A

BUN

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17
Q

__________ represents the volume of plasma that is cleared of a given solute per minute.

A

Clearance

Cx = (Ux)(V)/(Px)

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18
Q

Normal Cr clearance is ________ for females and _________ for males

A

≈85-125 ml/min for females
≈97-140 ml/min for males

Clearance of a secreted substance will be greater than Ccr, thus greater than GFR

Clearance of reabsorbed substances will be less than Ccr and less than GFR (ex: glucose, complete reabsorption, clearance is zero)

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19
Q

If GFR = 125 ml/min (from Cr plasma)
Px = 0.02 mg/ml
Ux = 0.10 mg/ml
V = 2.5 ml/min

Is Substance X secreted or reabsorbed?

A

Start with clearance:

Cx = (Ux x V)/Px = (0.10 x 2.5)/0.02 = 12.5 ml/min

12.5 < 125

Substance X is reabsorbed

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20
Q

If GFR = 125 ml/min
Px = 0.008 mg/ml
Ux = 2.5 mg/ml
V = 1.8 ml/min

Is Substance X secreted or reabsorbed?

A

Cx = (2.5 x 1.8)/0.008 = 562.5 ml/min

562.5 > 125

Substance x is secreted

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21
Q

If GFR = 125 ml/min
P(ur) = 0.15 mg/ml
U(ur) = 3.9 ml/ml
V = 2.5 ml/min

Is Urea secreted or reabsorbed?

A

C(ur) = (3.9 x 2.5)/0.15 = 65

65 < 125

Approximately 1/2 of filtered urea is reabsorbed

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22
Q 
For glucose:
GFR = 125 ml/min
P(glucose) = 1.0 mg/ml
U(glucose) = 0 mg/ml
V = 2.5 ml/min

Is glucose reabsorbed or secreted?

A

Because U = 0, and C = (UxV)/P so C = 0

100% of the filtered glucose is reabsorbed

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23
Q

Clearance ratios allow us to compare the clearance of any substance with…

A

Inulin clearance

Clearance ratio = C(x)/C(inulin)

If C(x)/C(inulin) = 1.0 the substance must also be a GFR marker (filtered, but neither secreted nor absorbed)

C(x)/C(inulin) < 1.0 —> Either substance is not filtered, or it is filtered and reabsorbed

C(x)/C(inulin) > 1.0 —> The substance is filtered and secreted

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24
Q

What does Para-Aminohippurate (PAH) tell us about renal plasma flow?

A

Since all the blood is cleared of PAH, C(PAH) is an estimate of RPF.

PAH in plasma —> some PAH is filtered —> all the remaining PAH is secreted —> all of the PAH is excreted in urine, none is left in the plasma

C(PAH) = (Upah x V)/Ppah = (540ml/min)(1)/(1) = 540 ml/min ≈ RPF

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25
Q

If we use PAH to estimate RPF, how can we determine renal blood flow (RBF)?

A

RBF = RPF/(1-Hct)

If Hct = 0.4 and RPF = 540 ml/min (from previous example):

RBF = (540)/(1-0.4) = 900 ml/min

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26
Q

The process by which a protein-free filtrate that is otherwise identical to plasma is produced

A

Glomerular filtration

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27
Q

The process by which waste products, metabolites, toxins etc are removed from the peritubular capillaries into the lumen of the tubule

A

Tubular secretion

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28
Q

The process by which valuable molecules (glucose, amino acids, etc) are moved from the tubular lumen back to the peritubular capillaries

A

Tubular reabsorption

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29
Q

_________ ≠ secretion, but is simply the loss of a substance from the body in the urine

A

Excretion

30
Q

The amount of a material in the glomerular filtrate is referred to as the …

A

Filtered load (FL, units are mg/min)

FL = (GFR)(Px)

31
Q

The amount of a material lost in urine is referred to as the …

A

Excretion rate (ER, units are mg/min)

ER = (Ux)(V)

32
Q

The amount of material added to (secreted) or removed (reabsorbed) from glomerular filtrate

A

Transport rate (Tx, units = mg/min)

Tx = FL - ER

33
Q

If transport rate is positive, then some material was …

A

Removed from the filtrate by reabsorption

34
Q

If transport rate is negative, then some material was …

A

Added to the filtrate by secretion

35
Q

Renal handling of different plasma constituents

A

Substance % Reabsorbed
Na+ 99.4
K+ 93.3
Cl- 99.2
HCO3- 100
Urea 53
Glucose 100
Total solute 98.9
Water 99.4

36
Q

The two routes for reabsorption

A

Paracellular (between cells in the “leaky” epithelium)

Transcellular (across the luminal membrane and basolateral membrane)

37
Q

Different mechanisms for facilitating transcellular reabsorption

A

Simple diffusion (usually via pores)

Facilitated diffusion (carrier mediated)

Primary active transport (NaK-ATPase, H+-ATPase, H/K-ATPase, Ca2+-ATPase)

Secondary active transport (reabsorption of AAs, glucose, lactate, citrate, phosphate, etc coupled to Na+ gradient)

Endocytosis

38
Q

By what mechanisms is glucose reabsorbed?

A

1) at the luminal/apical membrane, Glucose is transported into the cell by secondary active transport. (Note, much more glucose is moved than Na+)
2) at the basolateral membrane, glucose is transported into the ISF via facilitated diffusion

39
Q

______% of Na+ in the filtrate is reabsorbed in the __________.

A

67% in the proximal tubule

(Via Active Transport)

25% is reabsorbed in the LOH via active transport
8% is reabsorbed in the distal tubule and collecting duct via active transport (but subject to control by aldosterone)

40
Q

______% of water is reabsorbed in the ______

A

65% in the proximal tubule (via passive transport, or solute-linked)

15% in the LOH (also passive or solute-linked)
20% in distal/collecting duct but NOT solute linked - regulated by ADH

41
Q

In the distal tubule and collecting duct, ______ reabsorption is controlled by aldosterone and ______ reabsorption is regulated by ADH.

A 
Na+ = aldosterone
Water = ADH
42
Q

Na+ is transported across the basolateral membrane back into the peritubular capillary by …

A

The Na+/K+-ATPase.

Water follows Na+ passively via diffusion

43
Q

What drives fluid movement from the nephron lumen into the peritubular capillaries?

A

1) Active transport of Na+ across the basolateral membrane
2) Slight osmotic gradient then “pulls” water from the nephron lumen into the basolateral compartment
3) Anions (Cl- etc) follow Na+
4) π(PC) is the primary force driving fluid movement from the BL compartments into the peritubular capillaries

44
Q

Reabsorption of water and electrolytes is considered to be __________ in the proximal tubule

A

Isosmotic

45
Q

Mechanisms for reabsorbing Na+, Cl-, glucose, phosphate, citrate, lactate, and amino acids in the proximal tubule

A

Na+ enters PT cells via cotransport w/ organic and Na+/H+ antiport

Cl- enters peritubular capitallry via paracellular routes (and other routes)

Na+ leaves the cell by Na+/K+ ATPase or via contransport with HCO3-

46
Q

How does Angiotensin II influence Na+ reabsorption by the proximal tubule?

A

Stimulates Na+/H+ exchange a rose the apical membrane (NHE family of transporters)

Increases Na+ reabsorption and H+ secretion

47
Q

How does sympathetic nerve activity influence Na+ reabsorption by the proximal tubule?

A

Stimulates Na+ reabsorption

48
Q

How does Parathyroid Hormone influence Na+ reabsorption by the proximal tubule?

A

Inhibits Na+/phosphate cotransport

Increases urinary excretion of phosphate

49
Q

The tubular fluid to plasma concentration ratio (TF/P) for freely filtered solutes in Bowman’s capsule is…

A

1

Because the only thing that doesn’t get filtered is proteins, so the tubular fluid and plasma concentrations for every other filterable solute is the same

50
Q

Water and solutes are reabsorbed along the length of …

A

The proximal tubule (PT)

51
Q

The TF/P ratio for ________ shows that the volume of the tubule fluid is decreasing

A

Inulin

Because inulin is neither secreted nor reabsorbed, its TF/P ratio rises at a constant rate as the you move down the proximal tubule

52
Q

________ can produce very small TF/P ratios

A

Reabsorption

53
Q

If TF/Px (tubular fluid to plasma concentration) = 1.0, then …

A

Reabsorption has been exactly proportional to the reabsorption of water

54
Q

If TF/Px (tubular fluid to plasma concentration) < 1.0, then …

A

Reabsorption of the substance has occurred to a greater extent than water

55
Q

If TF/Px (tubular fluid to plasma concentration) > 1.0, then …

A

Reabsorption of the substance has been less than water, OR there has been net secretion of the substance

56
Q

TF/P(inulin) (tubular fluid to plasma concentration of inulin) is used as a marker because:

A

Because it is only filtered (neither secreted nor reabsorbed), it’s concentration in the tube is solely determined by the movement of water

57
Q

In renal transport systems, the maximal rate at which a particular solute can be transported is referred to as the

A

Tubular Maximum (Tm)

Below the Tm, all of the filtered load is reabsorbed
The portion of the load above Tm is excreted

58
Q

Tubular maxima are primarily found in the ___________.

A

Proximal tubule, due to saturation of membrane transport proteins

59
Q

Tm for glucose describes the…

A

Maximum rate at which glucose can be reabsorbed.

Above Tm, glucose begins to appear in the urine (is excreted).

60
Q

For glucose the ___________ refers to the plasma concentration where glucose first appears in the urine

A

Threshold

Depends on the GFR and Tm

61
Q

Due to the heterogeneity of nephrons, not all nephrons have the same Tm, which can be visualized on the glucose titration curve as …

A

Splay

62
Q

Changing the GFR does not effect the _____ but it does effect _____.

A

Does not effect Tm (transport maximum is a constant)

DOES effect Threshold

Example:
Decreasing GFR increases the threshold (plasma concentration at which you will see the substance in urine)
Increasing GFR decreases the threshold

63
Q

Examples of solutes that have Transport Maxima (Tm)

A 
Sugars (glucose, fructose, galactose)
Amino acids
Metabolic intermediates (lactate, ketone bodies, kreb’s cycle intermediates)
Phosphate ions
Water-soluble vitamins
Proteins and peptides
64
Q

An excess amount of an unreabsorbed solute (ie mannitol) __________ osmotic water flow from lumen to basolateral spaces

A

Inhibits

This is how osmotic diuretics like mannitol work)

Causes sodium back-diffusion into the lumen of the tubule —> increased loss of water and electrolytes in the urine

65
Q

__________ can result in a rapid loss of sodium and water (polyuria)

A

Osmotic diuresis

Example: mannitol, a non-reabsorbed carbohydrate can be given IV to induce an osmotic diuresis

Can accompany:
A high filtered load of urea
When the glucose load exceeds Tm in diabetic patients, the excess glucose in filtrate drives osmotic diuresis

66
Q

The two main transport mechanisms for tubular secretion are:

A

One transporter for organic cations
One transporter for organic anions

Both very non-specific

67
Q

How do the kidneys know to secrete metabolites, waste products, or foreign chemicals?

A

They are “tagged” (conjugated) by the liver, turning them into cations/anions

68
Q

Organic anions are secreted via …

A

Tertiary active transport

At the basolaminar membrane, the Na/K ATPase allows for the secondary transport of alpha-KG into the cell via secondary tranport. The aKG then is exchanged for PAH via the OAT (organic anion transporter), making it a tertiary active transport system.

The PAH then leaves the cell on the apical side via a PAH-anion antiporter

69
Q

Most organic anion secretion involves OAT-1 and OAT-3 transporters located in the…

A

Basolateral membranes of proximal tubule cells

70
Q

Organic cation transport is handled by…

A

Several OCT transports, also located in the proximal tubule

71
Q

Organic anion transporters (OAT) and cation transporters (OTC) exhibit…

A

Saturation kinetics, and therefore have a Transport Maximum (Tm)

72
Q

Most secretion occurs in the …

A

Late proximal tubule

True for both organic cations and anions

Phys II Unit 1 (10 decks)

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