Lecture 3: Proximal tubule/Concentration and Dilution Flashcards

1
Q

After the glomerulus, list the order of the renal tubules. (6)

A
  1. Proximal (convoluted) tubule
  2. Thin descending limb
  3. Thin ascending limb
  4. Thick ascending limb
  5. Distal (convoluted) tubule
  6. Collecting duct (Cortical collecting duct and Medullary collecting duct)

Loop of Henle is tubules 2-4

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2
Q

What is the location of the proximal tuble?

A

Closest to the glomerulus

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3
Q

What direction does reabsorption occur?

A

From the tubule to interstitum (capillary)

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4
Q

What is the main ion we reabsorb in the renal tubles?

A

Na+

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5
Q

Where is Na+ reabsorption quantitatively the greatest and how much is being reabsorbed?

A

Proximal (convoluted) tuble=67%

Reabsorption of most other tubules (and isosmotic reabsorption of water) is also greatest in the PCT

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6
Q

In the proximal tubule what is the driving force for reabsorption?

A
  • 3 Na+/2K+ ATPase
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7
Q

How does the 3Na+/2K+ ATPase drive reabsorption in the PT?

A
  • Creates gradient to allow Na+ in from the tubule by ↓ Na+ in the cell
  • Moves 3 Na+ into interstium and 2 K+ into the cell

This gradient ↑K+ in ICF and ↑Na+ in ECF

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8
Q

Explain why there is an isosmotic reabsorption of water in the PT.

A

Water follows Na+, so there is NO change is osmolarity

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9
Q

Using the chart below explain why the concentration changes from the bowman’s capsule to the late proximal tubule of substances; Inulin, Na+, Cl-, K+, Glucose, Amino acids, and protein

A
  • Inulin conc. increased b/c ↑H2O reabsorption in the late P.T.
  • Na+, Cl- and K+ all stayed the same d/t isotonic reabsorption= no 𝚫 osmolality
  • Glucose and A.A decrease to 0 b/c of reabsorption driven by the Na+ symporter (cotransporter)
  • Protein decreased to 0 b/c it was absorbed back into the kidney, cannot be filtered by the glomerulus
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10
Q

In Proximal tubule reabsorption, what generates the gradient? and what substance(s) does it reabsorb?

A
  • A 3Na+/2K+ ATPase on the basolateral capillary side
  • Complete reabsorption of Glucose, A.A. and HPO4-/SO4- w/ Na+ dependent symporters (cotransporters) on the apical lumen side
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11
Q

What is the role of the Na+/H+ antiporter (exchanger) on the proximal tubule?

A
  • Moves Na+ into the cell and H+ out of the cell
  • The H+ binds to bicarb in the lumen which helps regulate pH
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12
Q

What is the transporter on the lumen side of the PT that helps w/ the reabsorption of glucose?

A
  • SGLT1 (Sodium-glucose cotransporter)
  • Active process driven by Na+ gradient
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13
Q

What is the carrier on the PT. that helps reabsorb into the capillary (basal membrane)?

A
  • GLUT 2 (Glucose transporter 2)
  • Passive transport w/ carrier protein
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14
Q

Using the graph below, that shows the Reabsorption of Glucose explain what is occuring at

  • # 1,2, and 3
  • Letter a
  • Green and red circles
A
  • 1(Filtered): More glucose in the plasma, more glucose will be filtered; ↑ [glucose]= ↑ filtration rate
  • 2 (Excreted): Filtered [glucose]-Reabsorbed [glucose]
  • 3 (Reabsorbed): Driven by Na+/Glu transported and carrier (can reach Vmax when saturated)
  • a: gradual shut off-carriers reach Vmax at different times
  • Green circle: Are the same b/c what is being filtered is also being reabsorbed
  • Red circle: Now filtration=excretion b/c symporter is saturated and cannot reabsorb w/ such ↑ [glucose]
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15
Q

Explain the lines on the graph below for the substances: Inulin, Cl-. Na+ osmolarity, HCO3-, Glucose and amino acid.

The graph shows Tf/p on y-axis and PT length on x-axis

Tf/p=concentration of a substance in the tubular fluid compared to its concentration in plasma

A
  • Inulin (red line): conc. increased b/c ↑H2O reabsorption in the late P.T.
  • Cl- (dotted red line): reabsorption occurs later in the PT (b/c no more reabsorption of Na+ w/ glucose or HCO3-)
  • Na+ osmolarity (blue line): no change
  • HCO3-(green line): reabsorption occurs later in the PT
  • Glucose & A.A (gray line): rapid decrease in first 25% of tubule b/c reabsored quickly
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16
Q

Where and how does NaCl get reabsorbed?

A
  • In the late PCT
  • Cl- transporters

Review slide 10

PCT= proximal convulated tubule

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17
Q

How does Na+ and Cl- cross the PCT into the capillary?

A
  • Transcellular (2/3)- Na+/H+ antiporter and Cl-/formate antiporter
  • Paracellular (1/3)-d/t change in electrical gradient from the positive lumen side to negative capillary side

Review slide 10

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18
Q

How is water reabsorbed in the PCT?

A

Passively reabsorbed via transcellular and paracellular d/t the osmotic gradient established by transport of NaCl

Review Slide 11

Additional solute (e.g., Ca2+) is carried along via solvent drag

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19
Q

How much salt and water is reabsorbed in the proximal tubule?

A

2/3

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20
Q

How much glucose and amino acids are reabsorbed in the proximal tubule?

A

All of it (100%)

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21
Q

Proximal tubule reabsorption is _________.

A

Isotonic (PT osmolality is isotonic at the beginning & the end)

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22
Q

Where in the nephron does NO Na+ reabsorption occur?

A

In the thin descending and ascending limb

23
Q

What is the permeability of solute and water in the thin descending limb of the loop of Henle?

A
  • Low permeability to solutes
  • High permeability to water

Review Slide 15

24
Q

What are two things that occur at the thin descending limb because of the movement of H2O?

A
  • ↑ osmolarity b/c water leaves the thin descending limb
  • ↑ H2O in the interstitum

Review Slide 15

25
Q

How much reabsorption of Na+ occurs in thick ascending limb?

A

25%

26
Q

What is the thick ascending limb of the loop of Henle (TAL) also called?

A

Diluting segment

27
Q

What is the permeability of solute and water in the thick ascending limb of the loop of Henle?

A
  • Special carriers co-transport ions from tubule to interstitium→Na+/K+/2Cl transporter
  • Imperable to H2O (cannot leave)

Review Slide 17

28
Q

Why does osmality drop in the thick ascending limb?

A
  • Carriers remove Na+, K+, and Cl- (Na+/K+/2Cl- transporter)
  • Dilution increases because ions are leaving

Review Slide 17

29
Q

What does the Counter Current Multipler create?

A

An osmolarity gradient that increases osmlarity as we move from the cortex to the medulla (from proximal tubule to collecting duct) to concentrate urine

Review Slide 18

30
Q

Explain the mechanism of the Counter Current Multiplier

A
  • The solution leaving the glomerulus and entering the PCT is isosmotic (300 mOsm/L)
  • While in the PCT the solution stays isosmotic b/c equal amount of H2O and solutes are being reabsorbed
  • In the thin descending limb there is ↓ permeability to solute but ↑ permeability to H2O, so water leaves the tubules into the interstitum making the interstitum more diluted and the tubule more concentrated
  • The solution in the thin ascending limb is hypertonic b/c it is very concentrated
  • In the thick ascending limb there is a ↑ permeability to solutes b/c of the 3Na+/2K+ ATPase channel, this causes the osmolarity in the interstitium to increase, and the osmolarity in the tubule to decrease
  • The solution that enters the distal (convoluted) tubule is diluted or Hypoostamic
  • The early DCT has NaCl cotransporter which increased the osmolarity of the interstitium and decrease osmolarity of the tubule

Review Slide 19

31
Q

What is the Counter Current Exchange? and what is its function?

A
  • A function of the vasa recta capillares
  • Fx: (runs opposite of the tuble) To provide nutrients and O2 to deep kidney while maintaining the gradient created by the multiplier. Does this by:
    1. Maintaining the Na+ and Cl- collected
    2. Preventing the excess flow of fluid and solutes

Review Slide 19

32
Q

Explain the mechanism of the Counter Current Exchange?

A
  • At the descending vasa racta Na+, Cl- and urea move into the capillaries and H2O exits (picks up solutes b/c hypertonic)
  • At the ascending vasa recta Na+, Cl- and urea move out of the capillaries and H2O enters (drops off solute b/c hypotonic)

Review Slide 21

33
Q

How much Na+ is reabsorbed in the distal convulated tubule?

A
  • Early DCT=5 %
  • Late DCT= 3%
  • Total=8%
34
Q

What can be controlled in the distal convulated tubule?

A

Hormone systems of the body

35
Q

What transporter is present in the early distal convulated tubule?

A

Na+/Cl- Symporter

Review Slide 24

36
Q

What changes does the Na+/Cl- symporter in the distal convoluted tube cause?

A

The osmolarity in the tubule dilutes further (150 to 60) b/c Na+ and Cl- are moving into the interstitium

37
Q

What are the two parts of the collecting duct?

A
  • Cortical collecting duct (CCD)
  • Medullary collecting duct (MCD)
38
Q

The cortical collecting duct (CCD) is the site of what action?

A

ADH (antidiuretic hormone/vasopressin)

The action occurs @ principal cells

39
Q

Which two cells are present in the cortical collecting duct and what are their functions?

A

1. Principal Cells

  • Absorb Na+ and secrete K+
  • Where ADH action occurs

2. Intercalted cells

  • Secrete acid/base equivalents and can also reabsorb K+
40
Q

What is the function of ADH?

A

To increase tubular permeability to water

41
Q

Explain how ADH increase tubular permeability in the CCD?

CCD-Cortical collecting duct

A
  • Normally, the lumen side (apical) of the CCD has NO water channels making it imperable to H2O, while the blood side (basolateral) has water channels (AQP3&AQP4) making it permeable to H2O
  • Binding of ADH to the basolateral membrane of the principal cells results in the insertion of water channels (AQP2) into the apical membrane making the whole tubule imperable to water

Review Slide 28

AQP-Aquaporin

42
Q

Explain the steps of how AQP2 is added to the apical membrane (lumen side) of the principal cell

A
  1. ADH binds to Gs (G-protein coupled receptor) which activates adenyl cyclase
  2. AC w/ ATP activates cAMP
  3. cAMP activates protein kinase A
  4. Protein kinase A causes phosphorylation which increases the transcription and insertion of Aquaporin–2 channels to the apical membrane

Review Slide 28

43
Q

In the absence of ADH, what happens to the AQP2 water channel?

A

The channels are recycled and the apical membrane is again impermeable to water

44
Q

What is the concentration of solutes and water in the cortical collecting duct and medullary collecting duct?

A
  • In the cortical collecting duct concentration is diluated initiallyaddition of ADH causes water to leave duct increasing conc. of solute in the duct and increasing conc. of H2O in the interstitum causing the medullary collecting duct to be concentrated
  • Outcome is concentrated urine leaving the medullary collecting duct

Review Slide 29

45
Q

What is another substance that ADH affects in the CD?

A

Urea

46
Q

What mechanism does ADH use to increase the reabsorption of urea in the MCD?

MCD-Medullary collecting duct

A
  • It increases urea transport (UT1)
  • Urea diffuses from tubular fluid into interstitial fluid of inner medulla
47
Q

What happens to the urea that is diffused out of the MCD?

A

Picked up by the vasa recta and recycled

48
Q

What are the main ADH actions on the Kidneys (4)

A
  1. Increase permeability of entire Collecting Duct to water
  2. Increase permeability of Medullary CD to Urea
  3. Decrease Vasa Recta blood flow
  4. Increase expression of the Na/K/2Cl transporter in the Thick Ascending Limb

NOTE: Ask yourself how each of these effects increase the conc. of urine

49
Q

There is a high medullary interstital osmolality (1200 mOsm/L) in the nephrons. Explain how the mechanism below help maintain this:

  • Counter Current Multiplication
  • Counter Current Exchange
  • Importance of Urea
A
  1. Counter Current Multiplication: Reabsorption of Na+ and Cl- in the thick ascending limb (diluting segment)
  2. Counter Current Exchange: Low flow through vasa recta
  3. Importance of Urea: Acts as solute to help maintain osmolality

Review Slide 32 and 33

50
Q

True or False? Most of the filtrate is absorbed in the thick ascending limb of the loop of Henle

A

FALSE

Most absorbed in the proximal tubule

51
Q

True or False? Fluid leaving the Proximal tubule is isoosmotic to plasma

A

TRUE

52
Q

True or False? Renal medullary is primarily dependent on passive mechanism

A

FALSE

Dependent on active reabsorption of Na+, K+ and 2 Cl-

53
Q

True or False? Most reabsorption in the renal tubules is directly or indirectly dependent on Na+/K+ ATPase

A

TRUE

54
Q

True or False? ADH increase water absorption in most parts of the renal tubule

A

FALSE

Only in the Collecting duct