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Renal Exam 1 > Renal Transport Mechanisms > Flashcards

Renal Transport Mechanisms Flashcards

1
Q

Transepithelial transport must occur through 5 different barriers. What are they?

A
  1. Apical luminal membrane
  2. Cytoplasm of the tubular cell
  3. BL membrane
  4. Interstitial fluid
  5. Capillary membrane, to enter the plasma of the peritubular capillary.
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2
Q

Why do we filter 180 L/day and then reabsorb 99% of it?

A

1. Too much of something can be toxic. Thus, we need to filter (without reabsorbing) and secrete things.

2. Filtering ions and water into the tubule makes regulation easy. Thus, if unwanted filtrate reaches the distal nephron and is not needed, we excrete it.

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3
Q

What is reabsorbed in the proximal convoluted tubule?

(70% of things are rebsorbed into from the proximal tubule)

A
  1. 100% of glucose and AA.
  2. 65-70% of Na+ and water
  3. 70% of K+, Phosphate, Ca2+
  4. 50% of urea
  5. 30% of Mg2+
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4
Q

What is reabsorbed in the proximal straight tubule?

A
  1. 15% of phosphate
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5
Q

What is reabsorbed in the thick ascending limb?

A
  1. Na (25%)
  2. K (20%)
  3. Cl (25%)
  4. Mg (60%)
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6
Q

What is reabsorbed in the distal convoluted tubule?

A

1. H20 and urea are variable, depending on the bodies needs

2. Na (5%)

3. Ca2+ (8%)

4. Mg (5%)

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7
Q

What is reabsorbed in the collecting duct?

A

1. H20 and urea are variable, depending on the bodies needs.

2. Na+ (3%)

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8
Q

Where does the majority of reabsorption occur?

A

Proximal tubule (65-75%)

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9
Q

What is the key player in helping with reabsorption in the proximal tubule?

A

Reabsorption in the proximal tubule of everthing utilizes the Na/K+ ATPase pump that located on the basolateral membrane.

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10
Q

How do changes in concentrations in the proximal tubule occur?

A

PCT is freely permeable to water.

As solutes are reabsorbed, osmosis occurs and water is reabsorbed.

This will affect the gradient of solutes in the tubule.

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11
Q

What are the different ways to reabsorb things?

A

1. Transcellular transport--> mediated transport that occurs through the cell. Transcellular usually requires active transport across one membrane and passive transport across the other

  • -High–> low concentration: Passive transport
    • Low –> high concentration: Active transport

2. Paracellular transport–> diffusion between the cells down the concentration gradient.

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12
Q

What is facilitate diffusion?

A

Facilitated diffusion–> the movement of one solute involves the interaction of a protein in them membrane.

  • Symport (via a transporter/symporter)- 2 solutes move in the same direction
  • Antiport (via antiporter)- 2 solutes move in opposite direction
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13
Q

T/F: At least one solute must be transported against its gradient.

A

TRUE.

Energy to do this is derived from the passive movement of at least one other solute, typically Na+.

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14
Q

Does water follow sodium, or vice versa?

A

Water follows Na+.

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15
Q

Na+K ATPase pump is the main player of reabsorption and keeps it going.

How does it do so?

A

Na+ will undergoes active reabsorption

  • In active transport, substances are transported across a membrane utilizing another energy source. Although the movement of Na+ into cells is passive, overall process of reabsorption is active because of the role of Na/K ATPase pumps on BL membrane.
    1. Na/K ATPase pump will decrease [intracellular Na+], increase [intracellular K+],
    2. Low intraceullar [Na+] is made and so is a negative charge.
    3. Na+ moves across the apical membrane through Na+ leak channels –> cell.

Depending on the Na+ transporter, the inside of the cell will become negative with respect to the tubular lumen.

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16
Q

The main player of reabsorption if the Na+/K+ ATPase pump.

How is [Na+ reabsorbed] in the proximal tubule.

A

[Na+] tubular fluid= 140mEq.

[Na+]intracellular= 12mEq.

This creates a concentration gradient.

Na+/K+ ATPase pump on the BL membrane moves Na+ from [cell–> blood] and K+ into the cell, creating a low intracellular [Na+] and a negative charge. This keeps reabsoprtion going.

Therefore, Na+ will undergo active reabsorption

  • In active transport, substances are transported across a membrane utilizing another energy source. Although the movement of Na+ into cells is passive, overall process of reabsorption is active because of the role of Na/K ATPase pumps on BL membrane.

Na+ passively moves across the apical membrane (high–>low energy) via Na+ leak channels. The energy produced is then used to power secondary active transport (Na/K pumps) on the basolateral membrane.

Na+ then moves actively from inside the cell–>outside the cell across the basolateral membrane. (low–>high concentration).

  • Na, H20 and other substances are reabsorbed from ISF–> peritubular capillaries via ultrafiltration (which is d/t hydrostatic and osmotic pressure gradient)
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17
Q

The interior of the cell is +/- with respect to the tubular lumen, due to what?

A

-

Na+/K+ transporter.

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18
Q

What are examples of co-transporters in the kidney?

A

1. NaK2Cl co-transporter

2. NaCl co-transporter

3. NaHCO3- co-transporter

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19
Q

What are [counter-transporters] in the kidney?

A

1. Na+/H+ exchanger

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20
Q

What are the channels in the kidney?

A

1. Aquaporins

2. Na+

3. K+

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21
Q

Why doesnt everything go through paracellular transport?

A

Leaky tight junction only allow some ions (Ca2+. Mg, K and Na+) to use this route.

And water.

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22
Q

Water can undergo transcellular and paracellular movement. Is ATP required?

A

No, water does not require ATP to move.

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23
Q

Solutes can undergo transcellular and paracellular movement. Is ATP required?

A

Yes.

Paracellular route occurs through passive transport and thus, ATP is not needed.

Transcellular route for solutes occurs via active transport and requires ATP.

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24
Q

How much Na+ is filtered, excreted, reabsorbed and what is the filtered load reabsorbed?

A

25, 200 mEq are filtered everyday.

150 mEq are excreted everyday.

25,050 are reabsorbed every.

Thus, the filtered load reabsorbed is 99.4%.

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25
Q

Na+ reabsorption is active, as we have said and occurs via the ______ route.

It is the key to reabsorbing other substances in the proximal tubule.

A

Transcellular

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26
Q

Describe the process of Na+/H+ exchange in the proximal tubule.

A

80% of the Na+ that is reabsorbed into the tubular cells is exchanged for H+ via the NHE3 transporter, located on the apical membrane of the proximal tubule.

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27
Q
  1. How does the body provide a sufficent amounts of intracellular H+ to feed the exchange?
  2. What happens to all of the H+ ions that enter the lumen of the tubule?
A

Carbonic anhydrase is located in the proximal tubule and

converts CO and H2O–> Bicard and H+, and vice versa.

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28
Q

Describe the process of Cl- Reabsorption in the proximal tubule.

A
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29
Q

Water can move paracellular or transcellulary.

Paracellular movement depends on the presence or absence of tight junction.

Thin descending limb has _____ tight junctions.

Thick ascending limb and the collecting duct has _____ tight junction.

A

Thin descending limb has few tight junctions, allowing water to move paracellularly.

Thick ascending limb and the collecting duct has many tight junction, preventing water from moving paracellularly.

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30
Q

How does water move transcellular, through the cells?

A

Via aquaporin channels (Aqp 1 and Aqp 2).

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31
Q

Where are aquaporin 1 and aquaporin 2 located?

A

Aquaporin 1–> proximal tubule

Aquaporin 2–> apical membrane of collecting duct, where they are controlled by ADH

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32
Q

The net permeability of the renal tubule is dependent on?

A
  1. Presence of absence of tight junctions (control paracellular movement)
  2. Presence or absence of aquaporin channels (controls transcellular movement)
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33
Q

Tight junctions and aquaporins in the

-Proximal tubule

-Descending limb

-Ascending limb of the tubule

-Collecting Duct

A

Proximal tubule–> many tight junctions and many Aqp1 channels = permeable to water

Descending limb--> not many tight junctions and many Aqp1 channels= permeable to water

Ascending limb--> many tight junctions and NO aquaporin channels= impermeable to water

Collecting duct–> has Aqp2 channels, which is regulated by ADH= permeable to water

34
Q

Permeable or impermeable to water?

  1. Proximal tubule–>
  2. Descending limb–>
  3. Ascending limb (thick and thin)–>
  4. Collecting duct–>
A
  1. Proximal tubule–> permeable
  2. Descending limb–> permeable
  3. Thick and thin ascending limb–> impermeable
  4. Collecting duct--> permeable, depending on needs of the body.
35
Q
A

Loop of henle filters less water because the thin and thick ascending loop are impermeable to water. Thus, the 15% of water absorbed in the LOH is d/t the thin descending limb.

  • Late distal tibule and CD reabsorption percentages are variable based on body needs.
36
Q

Describe the process of glucose transport in the proximal tubule

A

Glucose is only re-absorbed in the proximal tubule.

It is co-transported with Na+.

[insert pic]

37
Q

Why is glucose reclamation important?

A

Reclaiming Glu is important because we need it for metabolism and it must be transported into all cells in the body.

38
Q

What are the two types of glucose transporters?

A
  1. SGLT-1
  2. SGLT-2
39
Q

What is the relation between affinity and concentration?

A

A high affinity system requires a lower concentration to fill all of the binding sites.

A low affinity system requiers a higher concentration to fill all of the binding sites.

40
Q

Describe SGLT-1

A

-Responsible for 10% of reabsorption in segment 3 of the proximal convuluted tubule, where Glu concentrations are lower.

  • High affinity
  • Low capacity

Thus, even when [Glu] is low, they are active.

41
Q

Describe SGLT-2

A

-Responsible for 90% of glucose reabsorption in segment 1 and 2 of the proximal convoluted tubule

  • Low affinity
  • High capacity transport

-

42
Q

What glucose transporters are located in:

  1. Segment 1 and 2 of the proximal convoluted tubule
  2. Segment 3 of the PCT
A

SGLUT2 and GLUT2 are located in segment 1 and 2 of the proximal convoluted tubule

SGLUT1 and GLUT1 are located in segment 3 of the PCT

43
Q

How can we treat Type 2 Diabetes?

A

Type 2 diabetes can be treated by inhibiting renal SGLT2;

this will decrease blood glucose levels by decreasing glucose reabsorption.

44
Q

What is the glucose levels in someone with DB?

A

A person with DB will have high blood glucose due to increase glucose reabsorption.

45
Q

What is the transport maximum of glucose and the plasma glucose levels?

A

Tm= 375mg/ min

Plasma glucose levels= 200mg/dL

46
Q

LOOP OF HENLE

LOOP OF HENLE

LOOP OF HENLE

LOOP OF HENLE

LOOP OF HENLE

A
47
Q

What is permeable and impermeable in the descending LoH?

A
  1. H20–> permeable (15% of filtered water is reabsorbed)
  2. NaCl–> impermeable
48
Q

What is the result of the descending LoH being permeable to H20 but not NaCl?

A

Descending Limb of LOH progressively hyper-osmotic/hypertonic as water leaves and the solute concentration in the tubular fluid increases

49
Q

Thin and thick ascending LoH

A

The ascending LoH is

  • Impermeable to H20.
  • 35-40% of NaCl is reabsorbed via the Na/K/2Cl co-transporter.

Reabsorption of [Na, Cl, K] causes the filtrate to in the tube to become more dilute (hypo-osmolar) as it flows to the distal tubule.

50
Q

How is reabsorption of Na+ in the thick ascending loop different from the proximal tubule?

A

PT- Na+ reabsorption is coupled with organic solutes,

However. in the ascending loop, almost all of the glucose and AA were removed.

Because only Na+ is reabsorbed and water is not, the Na+ concentration gets to its minimum= 50-75 mEg/L at the end of the thick ascending limb (vs 140 mEg in the proximal tubule).

51
Q

Descending limb–> water is reabsorbed, but not particles

Ascending limb–> particles are reabsorbed, but not water. What does this cause?

A

Thick ascending limb will dilute the filtrate.

75% of the particles that NTR the ascending limb are reabsorbed.

52
Q

Ascending limb has an intense job: reclaim particles.

How does it do so?

A

It has a high density of Na/K ATPase on the BL membrane,.

53
Q

Describe the reabsorption that occurs at the thick ascending limb?

A

Na/K/2CL co-transporters are located on the apical tubular lumen.

Na/K ATPase is located on the BL side.

[insert picture]

54
Q

What is the net effect of reabsorption in the ascending LoH?

A

1 positive charge and 2 negative charges have been reabsorbed, leading to a transepithelial positive voltage (+3-+10 mV).

–>

Cations move, like Na+, Ca2+ and Mg2+ move from the [lumen–> BL] via paracellular transport

–>

Reabsorption of Ca2+ and Mg2+ in the thick ascending limb regulates serum levels and storage.

-

55
Q

How will blocking

Na/K/2Cl transporter, K+ recycling or BL CL- channel will do what?

A

Block reabsorption of the cations.

56
Q

How will a low K+ diet or K+ depletion affered reabsorption/secretion?

A
  1. Decreses secretion in the [DCT cells, principal, CT and cortical collecting duct].
  2. Decrease reabsorption in the cells that contain [H/K ATPases] and [CD in the medulla]/
  3. Urine output decrease to 2%.

High K+ diet will increases (1) and increase urine production to 150%.

57
Q

Describe the countercurrent multiplier?

—Descending loop is only permeable to water—

—Ascending loop is only permeable to solutes—

A
58
Q

By the time that filtrate reaches the DCT, we only have 10% of the originally filtered NaCl and 25% of the water.

Describe the permeability of the distale tubule

A
  1. Reabsorbs 5%-8% of NaCl via the Na/Cl- transporter
  2. Early part of the distale tubule= impermeable to H20
  3. Late part of the distale tubule= permeable to H20
    * Thus, it is relatively impermeable to H20.*
59
Q

Na+/Cl- Cotransport in the Distal Tubule

A

Na/Cl- co-transporter is located on the apical membrane.

  1. Na+ and Cl- are moved into the cell via the Na+/Cl co-transporter
  2. Na+/K ATPase will remove Na+ from inside the cell.
  3. Cl- leaves via Cl- channels
60
Q

How does the Na+Cl co-transporter differ from the Na/K/2Cl?

A

Na/Cl Co-transporter is blocked by thiazide diuretics.

61
Q

What do thiazide diuretics do?

A

Thiazide diuretics block the Na/Cl- co-transporter in the distal convulted tubule, decreasing the amount reabsorbed and increasing the amount of Na and Cl excreted.

  • -They also increase Ca2+ reabsorption in the DCT by increasing Na/Ca2+ exchange, and thus, decreasing excretion of Ca2+.

Tx: Calcium-subtype kidney stones and osteopororsis

62
Q

Collecting Duct Reabsorption

A

Reabsorption in the collecting duct is regulated by hormones, based on the bodies needs.

  1. Aldosterone release reabsorbs Na+ to fine-tune.
  2. ADH release reabsorbs water.
  3. PTH release reabsorbs Ca2+.
63
Q

Reabsorption in the collecting duct is regulated, based on the bodies needs.

What hormones regulate reabsorption in the CD?

A

1. Aldosterone regulates Na+

2. ADH regulates water

3. PTH regulates Ca2+

64
Q

If we do not have ADH, what happens to water reabsorption in the CD?

A

CD becomes IMPERMEABLE to water.

65
Q

Aldosterone can be secreted by 2 different pathways.

What causes the release of aldosterone into the blood?

A

4 will directly stimulate the secretion of aldosterone from adrenal ctx

1. Decreased BV [decreased ECF]

2. Decreased BP [dec arterial pressure]

3. Low extracellular [Na+] (hyponatremia)

4. High extracellular [K+] (hyperkalemia)

1-3 will promote aldosterone secretion via the RAAS system.

66
Q

Except hyperkalemia (which directly stimulates the adrenal CTX to secrete aldosterone), these conditions do what?

A

promote RAAS sysyem, to release aldosterone

67
Q

What cells does aldosterone target?

How does it cause us to retain NaCl and H20?

A

Principal cells in the distal part of the DCT and the CD,

resulting in?

    1. Add apical Na+ channels on the CD to increase Na+ reabsorption
    1. Opens Na+ channels on the DT and CD to increase Na+ reabsorption
    1. Adds Na/K ATPase on the BL membrane.
    1. Adds more K+ channels on the apical membrane, allowing us to secrete more.

Aldosterone, thus, causes us to secrete more K+ and retain more Na+.

68
Q

What occurs when we have NO aldosterone?

A

Reabsorb less Na+, causing us to secrete 2% more Na, which is not compatible with life.

69
Q

Aldosterone is released from the adrenal CTX in response to angiotensin II or directly in response to an increase in _____ (not via RAAS system).

A

Plasma K+

-Promotes urination and elimination of excess K+

70
Q

Describe the pathway of aldosterone secretion

A

[pic]

71
Q

What is the goal of aldosterone?

A

Aldosterone acts on the thick segment of the nephone, DCT and the collecting duct located in the cortical area.

Its goal is to retain NaCl and water; decreasing urine volume, while increasing the concentration of K+ in the urine.

72
Q

Urea reabsorption

A

Urea is freely filtered at the glomerulus.

The amount we filter depends on our protein intake.

  1. Proximal tubule–> passively reabsorbs 5% of urea
  2. DTS and ascending thin segment of the nephron receive urea by diffusion from the interstitium –> lumen.
  3. Thick ascending limb and the DCT are impermeable to urea.
  4. Collecting duct in the medulla reabsorbs ALOT of urea via UT-A (urea transport protein), which is stimulated by ADH.
73
Q

____ stimulates the expression of UT-A.

What does this do?

A

ADH stimulates the expression of UT-A.

This, then increases permeability of the inner medullary collecting duct to urea–> increasing reabsorption.

74
Q
A
75
Q

HORMONE TRANSPORT CHART

frmo appendix B

A
76
Q

Diuretic inhibit transport and cause increase urine excretion. What are the 3 types?

A
  1. Thiazide diuretics
  2. Loop diuretics (furosemide)
  3. K+ sparing spironolactone
77
Q

Thiazide diuretics

A
  • Inhibits Na+ and Cl- reabsorption in the DCT
  • Increases Ca2+ reabsorption in the distal tubule
  • Induces natriuresis and decreases BV and BP
78
Q

Loop diuretics (furosemide)

A

-Inhibits the Na/K/2Cl co-transporter in the thisck ascending LoH.

–>

-Decreases Na+, K+ and Cl- reabsorption,

–>

Induces diuresis–> increased urine output.

79
Q

K+ Sparing Spironolactone

is a aldosterone dpeendent K+ sparing diuretic.

A
  • Inhibits Na+/K+ exchange in the distal tubule and CD.
  • Promotes K+ retention and Na+/water loss
  • Causes a hypotensive effect.
80
Q

What happens if we have a water deficit, often caused by excercise, decreased fluids or dehydration?

A

ADH increases

–>

distal tubule/collecting duct permeable to water. Water will leave tubule lumen and be reabsorbed.

–>

Therefore, we will excrete a small volume of concentrated urine. This happens when we have a reason to hold onto water.

[look at slide for more detail

81
Q

[look at slide 48]

A

Renal Exam 1 (10 decks)

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