Proximal Tubule Flashcards

1
Q

What percentage of all filtered solutes and H2O are reabsorbed in the proximal tubule?

A

2/3

-Sum of total osmoles reabsorbed is proportional to water, Iso-osmotic

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2
Q

What are three different mechanisms by which to move substances?

A
  1. Diffusion
  2. Channels
  3. Transporters
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3
Q

What is diffusion?

A

Movement down a gradient. Primary method across peritubular capillary and paracellular movement.
-Only non-charged particles!!

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4
Q

What are channels?

A

They facilitate diffusion across a lipid bilayer

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5
Q

What are transporters?

A

They are generally slower facilitators than channels due to the required tight substrate binding.

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6
Q

What is the function of Uniporters?

A

Single solute movement

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7
Q

What is the function of Multiporters?

A

Move 2 or more solutes simultaneously

  • Same direction (symporter)
  • Opposite direction (antiporter)
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8
Q

What is active transport?

A

Moving a solute up it electrochemical gradient!

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9
Q

What is primary active transport?

A

Need to burn energy to make it happen!

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10
Q

What is secondary active transport?

A

One solute moves down its electrochemical gradient & this produces other solute energy to go against its!

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11
Q

In the proximal tubule what is the only transporter that requires energy??

A

The basolateral 3Na+-2K+ transporter!!

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12
Q

What happens in terms of charge in the proximal tubule cells?

A

More positive change pumped out than in –> this maintains negative change in cell!

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13
Q

What happens to K+ on the basolateral side of the proximal tubule?

A

K+ is recycled!

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14
Q

What makes up the greatest amount of “stuff” in the urine?

A

Na+!! (140 mM)

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15
Q

What makes Na+ want to come into the cell at the proximal tubule?

A

HUGE concentration gradient!

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16
Q

What is the concentration of Na+ in the proximal tubule cell?

A

4-10 mM

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17
Q

What is a unique property to remember about the peritubular capillaries?

A

They are fenestrated!!

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18
Q

What different molecules is sodium cotransported with into the proximal tubule cells?

A
  • H+ pumped out of cell
  • Glucose pumped in
  • A.A. pumped in
  • PO4- pumped in
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19
Q

What type of transport does Na+ use when pumped in along with other molecules?

A

Carrier mediated transport

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20
Q

What are the SGLT?

A

Sodium-Glucose Linked Transporters
Two types: SGLT1, SGLT2
90% of glucose reabsorbed in proximal tubule via SGLT2!!

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21
Q

How much of filtered glucose is reabsorbed in the proximal tubule?

A

100%!!

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22
Q

What is the saturation point of Na+-glucose transporters referred to as?

A

Tm = Transport maximum

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23
Q

What happens when you reach the Transport maximum (Tm) of glucose?

A

Once it’s reached, additional glucose will NOT be able to be reabsorbed –> glucose will remain in the urine!

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24
Q

What amount of glucose in the urine is abnormal?

A

ANY GLUCOSE

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25
Q

What amount of glucose in the urine is referred to as glucosuria?

A

15 mM of glucose

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26
Q

What are some potential causes of Glucosuria?

A

Genetic/Proximal Tubule Disorder or DM!

27
Q

What carrier mediated transporters are located on the basolateral side of the proximal tubule cells?

A
  • Na+-HCO3- symporter
  • Glucose
  • A.A.
28
Q

In the proximal tubule glucose, A.A. and phosphorus are being pumped up their electrochemical gradient. How is this done?

A

Via 2ndary Active Transport!

29
Q

Where is Cl- reabsorbed?

A

Further down he proximal tubule –> because its concentration builds up as it flows through

30
Q

Where are most formate transporters located?

A

Late section of proximal tubule (where there is a favorable concentration gradient for Cl-)

31
Q

How is Cl- transported in the proximal tubule?

A

2ndary active transport.

-Pumped in while formate is pumped out!

32
Q

What does formate become outside the cell?

A

Formic acid (combined with H+)

33
Q

What produces formate in the cell?

A

HF breaks into H+ and formate

34
Q

What provides the H+ for formate outside the cell?

A

The Na+, H+ co transporter (Na+ in and H+ out)

35
Q

What are the three means by which Cl- gets into the peritubular capillary?

A
  1. Paracellular flow
  2. Formate transporter –> Cl- channel
  3. Formate transproter –> K+, Cl- cotransproter (carrier mediated)
36
Q

What is the purpose of formate in the proximal tubule cells?

A
  • Simply used to uptake Cl-

- Formate is just recycled!!

37
Q

What is important to remember about CrCl?

A

It is an estimate for GFR but it ALWAYS overestimates!

38
Q

What should you know about MDRD?

A

It’s a true predictor for GFR but you need to adjust for surface area or your calculation is wrong!
(ex: 1.72 m^2 is standardized)

39
Q

How much of the Bicarbonate that you filter is reclaimed in the proximal tubule?

A

80%

40
Q

What is interesting about Bicarbonate reabsorption?

A

It is technically put into the urine early on and then “recreated” in the proximal tubule and put into the bloodstream

41
Q

How is HCO3- transported in the urine?

A

HCO3- + H+ = H2CO3 = CO2 + H2O

Carbon dioxide and water

42
Q

What enzyme is responsible for making bicarbonate in the proximal tubule cells?

A

Carbonic anhydrase converts CO2 + H2O into H2CO3 into HCO3- and H+.

43
Q

What happens to the H+ and HCO3- made by carbonic anhydrase in the proximal tubule cells?

A
  • The H+ is pumped out into urine (while Na+ is pumped in)

- 3HCO3- is cotransported into the peritubular capillary along with Na+

44
Q

How is water transported/reabsorbed in the proximal tubule (3 ways)?

A
  1. H2O does minor diffusion into cell –> Aquaporins –> Peritubular capillary
  2. H2O enters cell through aquaporins –> enters peritubular capillary through aquaporins
  3. H2O is transported paracellularly
    - -> water is attracted into the cell because there is a high concentration of solute within the cell
45
Q

What does it mean when this equation is negative: [(Ppc + pii) - (Pi + pipc)]? Positive?

A

Negative - Reabsorption

Positive - Filtration

46
Q

In summary, what is reabsorbed in the Proximal Tubule?

A

100% Glucose
80% Bicarbonate
66% (2/3) Water, Na, Cl

47
Q

Why do we filter so much (180 L/day) in the kidney?

A

To get rid of TOXINS and take everything we need back!

48
Q

What happens to substances that don’t have channels or transporters?

A

They MUST diffuse across the cell membrane OR be excreted.

49
Q

What types of substances can diffuse across the cell membrane?

A

Non-polar substances (no charge!)

50
Q

What happens to polar substances in the urine?

A

They get trapped in the urine, you excrete them!

51
Q

What can the liver make if the body needs something excreted?

A

It can make a non-polar thing POLAR!

52
Q

What are examples of Polar substances?

A

Waste products, drugs, toxins [cytochrome P450 makes these polar]

53
Q

What happens to non-polar substances in the urine?

A

These can diffuse across the membrane and will not be secreted.

54
Q

What are examples of non-polar substances?

A

Steroid hormones, O2, Cholesterol, CO2

55
Q

What is NH4+ used for in the CELL and in the URINE?

A

To store large amounts of HYDROGEN while keeping the pH balance of urine!

56
Q

What is important to know about WOA and WOB in the proximal tubule?

A

Most of these you don’t need!

57
Q

What WOA/WOB do you NEED to SAVE in the proximal tubule?

A

Most physiologic WOA you need to save.

Ex: drugs, metabolites (usually arising form liver biotransformation)

58
Q

What is the most important WOA/WOB you need to SAVE?

A
Monocarboxylic acids (MCAs)
Ex: Pyruvate, Ketone bodies, Lactate
59
Q

What is special about the MCA transporter?

A

It pumps MCA into the cell along with Na+.

It recognizes a carboxylic group - so you can hang onto those you need (WOA and WOB) but get rid of anything else.

60
Q

What happens when the MCA transporter is interrupted?

A

Anything that interrupts this increases drug concentration/inhibits drug clearance.

61
Q

How do WOA and WOB get secreted in the urine?

A

OAT and OBT transport WOA and WOB actively into the cell. Then carrier mediated transporters provide facilitated diffusion of the WOA and WOB into the urine.

62
Q

What are the Mechanisms of Probenicid & Sulfinpyrazone?

A

They facilitate the excretion of Uric Acid via inhibiting OAT transporter.

63
Q

How do WOA and WOB get secreted from the peritubular capillary into the cell?

A

OAT and OBT transport WOA and WOB actively into the plasma.