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Renal System > Distal Tubule and Collecting duct > Flashcards

Distal Tubule and Collecting duct Flashcards

1
Q

Structures that make up the Loop of Henle (LOH)?

A
  1. thin descending limb
  2. thin ascending limb
  3. thick ascending limb
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2
Q

Major function of the LOH?

A

About 25% NaCl is reabsorbed in this segment by an active transport mechanism

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3
Q

Major function of the rest of the distal tubule (i.e. the distal convoluted tubule and collecting duct)?

A

Regulated reabsorption of about 5% of NaCl

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4
Q

Structure and location of the thin descending limb of the LOH?

A

Starts at the distal end of PT and runs from cortex to outer medulla

  • composed of Thin epithelial cells with few mitochondria
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5
Q

How does the interstitial environment of the renal medulla differ from other organs?

A

The fluid is Markedly hyperosmotic to plasma.

  • It is isosmotic to plasma at the border between cortex and medulla, but increases progressively downwards to a max of 1200 mOsml/L at the papillary tip.
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6
Q

Specific function of the thin descending limb of the LOH? How is this done?

A
  1. Concentration of Tubule Fluid (TF).
  2. This is achieved by the unique transport characteristics:
    - no active transport mechanisms.
    - IMPERMEABLE to NaCl and urea.
    - But, Highly water permeable due to the presence of aquaporins in the epithelial membranes.
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7
Q

How does the osmolarity change as the TF flows down the thin descending limb of the LOH?

A

Osmolarity of TF increases progressively as you move from the cortex down into the medulla (due to the reabsorption of water)

  • @cortex: 280 mOsmoles/kg H2O
  • @ Medulla: 1200 mOsmoles/kg H2O
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8
Q

What is the main driving force of water reabsorption in the thing descending limb of the LOH?

A

The osmotic gradient between the luminal fluid and IF.

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9
Q

Structure of the thin ascending limb?

A

Same as the thin descending:

- composed of Thin epithelial cells with few mitochondria

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10
Q

Difference in permeability between thin descending limb and thin ascending limb?

A
  • Thin ascending limb is impermeable to water to water (lacks aquaporins)
  • Thin ascending limb is high permeability to NaCl
  • *opposite the thin descending limb
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11
Q

How does the osmolarity change as the TF flows up the thin ascending limb of the LOH?

A

Osmolarity of TF decreases as it moves up.

  • due to the lack of water permeability and the high permeability of NaCl
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12
Q

Describe the flow of NaCl and H20 in the thin descending limb vs the ascending.

A

Thin descending: Concentration of TF

  • NaCl stays in
  • H20 flows out

Thin ascending:

  • NaCl flows out
  • H20 stays in
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13
Q

Permeability of Urea in the LOH?

A

impermeable

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14
Q

Structure of the thick ascending limb of the LOH?

A
  • consists of thick epithelium with lots of mitochondria in the cells
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15
Q

Major function of Thick ascending limb of LOH?

A

The main function is NaCl reasbsorption

  • occurs by active transport mechanism.
  • segment is impermeable to water
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16
Q

Flow of ions and water in the Thick Ascending limb of the LOH?

A

NaCl active transport by:

  1. Na+/K+/2Cl- transporter (luminal membrane of epithelium)
    - electro-neutral and driven by the electrochemical gradient produced by Na/K pump
  2. Na+/K+ ATPase pump (basolateral mem.)
  3. Other channels
    - Apical K-channel and Basolat. Cl-channels

-*H20 impermeable in Thick AL

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17
Q

How and where do diuretics act? result?

A

N/K/2Cl is sensitive to diuretics such as furosemide and bumetanide.
- They have high affinity to Cl binding site and block the activity of this channel (blocking NaCl reabsorption)

Result is: Delivery of more NaCl and isotonic fluid into the distal segments (i.e. more fluid excretion)

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18
Q

Effect of Vasopressin and ADH? How and where?

A

Stimulate NK2C and stimulate NaCl reabsorption

- cause opposing effect on diuresis.

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19
Q

Fact:
Loop diuretics are more efficient than other diuretics that act in DT due to high NaCl reabsorption in the loops compared to that in DT.

A

Fact:
Loop diuretics are more efficient than other diuretics that act in DT due to high NaCl reabsorption in the loops compared to that in DT.

20
Q

Structure of the Distal tubule (i.e. Distal to LOH?)

A
  • Distal Convoluted Tubule (DCT) starts after the thick ascending limb of LOH.
  • 6-8 DCTs join together to form the Collecting Duct.
  • DCT and CD have distinct cell types, but the functions are similar
21
Q

Describe the tubular fluid processing that occurs in the Distal Convoluted Tubules and Collecting Duct

A

Receive about 10% of filtered water, less than 10% of filtered Na, K and Cl, and 50% of urea.

  • Na is actively transported across the epithelium.
  • K is secreted into the lumen.
  • Na reabsorption > K secretion, and therefore Cl is reabsorbed

Result: Dilution of tubular fluid (if the tubule is impermeable to water- depends on plasma level of ADH)

22
Q

When is water permeable and impermeable in the Distal tubule? What determines this?

A
  1. Plasma osmolarity low due to excessive water drinking => low ADH => less water permeability in DCT => diuresis.
  2. plasma osmalarity high due to water deprivation => High ADH => More water permeability in the DCT => hyperosmotic urine (i.e. concentrated and yellow)
23
Q

Transport mechanisms in the DCT and CD

A
  1. Electrically conductive Na+ channel (ENAC)
    - diffusion of Na down electrochem. gradient
    - found in both DCT and CD
  2. Na-Cl co-transporter
    - ONLY in DCT
    - electro-neutral
24
Q

Which diuretics block ENAC in the distal tubule?

A
  1. Amiloride

2. triamterene

25
Q

Which diuretics block the Na-Cl co-transporter of the DCT?

A

Thiazide diuretics

26
Q

Which diuretics are more efficient, Loop-diuretics or diuretics acting in the distal tubule?

A

Loop-diuretics

- 10 fold more efficient

27
Q

What is unique about the epithelial membrane of the DCT and more so the CD?

A

both have: Lumen-negative transpithelial voltage

  • due to the activity of electro conductive Na channels creating more negativity in the lumen causing the membrane to depolarize
  • Major key for K+ secretion
  • CD > DCT
28
Q

Where and how does potassium secretion occur?

A

Occurs in the DCT and CD

- via passive diffusion through the apical K channel

29
Q

What two factors drive potassium secretion?

A
  1. High intracellular K concentration

2. Lumen-negative potential

30
Q

Factors that regulate potassium secretion?

A
  1. fluid flow – higher the fluid flow higher is K secretion.

2. Na delivery to DT – higher the Na delivery to DCT and CD greater the lumen-negative voltage and greater K secretion.

31
Q

effects of diuretics on K secretion?

A

Loop diuretics: increase K secretion (increased Na flow to DCT and CD and therfore higher lumen-negative voltage)

Thiazides: only minimal increase due to increased flow.

Amiloride: DECREASE K+ secretion. (reduce lumen-negative voltage, but slightly compensated by increased flow)

32
Q

What is Aldosterone and what/where is it’s effect?

A

Mineralocorticoid secreted by the adrenal cortex

  • regulator of Na reabsorption in distal tubule.
  • actions include Na reabsorption and K secretion.
  • Aldosterone acts exclusively in the DCT and CD!
33
Q

How does Aldosterone work? (MOA)

A

It’s cell permeable and binds to cytosolic and nuclear receptors and regulate gene expression related the expression of electro conducting Na channel, Na-Cl co-transporter, NKA and K channel in the DCT and CD epithelial cells.

  • It also increases the expression of Kreb’s cycle enzymes and ATP synthesis, all factors needed to increase Na reabsorption and K secretion.
34
Q

Aldosterone induced changes in cells? (7)

A
  1. open Na+ channel in apical membrane of DCT and CD
  2. inc transepithelial voltage
  3. inc Na+Cl- cotransporter
  4. inc synthesis of NKA, Kreb’s cycle enzymes, ATP synthesis
  5. inc basolateral surface area
  6. inc activity of apical membrane K+ channel
  7. inc Na+ reabsorption and K+ secretion
35
Q

Disease characterized by the complete absence of aldosterone production?

A

Addison’s disease

- Results in increased excretion of NaCl in the urine.

36
Q

Disease characterized by Aldosterone secreting tumors that maintain a high plasma level of aldosterone

A

Conn’s disease
- Results in increased Na reabsorption, K+ secretion and reduced urinary excretion of Na
(Hypokalemia, hypernatremia, hypertension)

37
Q

Conditions that increase aldosterone secretion (5)

A
  1. Reduced ECF vol. and C.O.
  2. Decreased plasma Na+
  3. Increased plasma K+
  4. High plasma Angiotensin II
  5. Trauma, stress
38
Q

Conditions that decrease aldosterone secretion

A
  1. Increased ECF
  2. Increased plasma sodium
  3. Decreased plasma K+
  4. Low plasma angiotensin II
  5. Low plasma ACTH levels
39
Q

What are the two cell types of the DCT and CT?

A
  1. Principal cells

2. Intercalated Cells

40
Q

What is the function of Principal cells of the DCT and CD?

A

involved in Na reabsorption and K secretion

41
Q

What is the function of intercalated cells of the DCT and CD? How does this occur?

A
  1. proton secretion
  2. HCO absorption (sometimes secretion)

-active transport process via a proton pump (Proton-Activated ATPase

42
Q

How does proton secretion in the DCT/CD differ from that in the PT?

A

DCT/CD = proton pump (NO diffusion)

PT = Na-H exchanger AND some diffusion

43
Q

How does the Proton-Activated ATPase of the DCT/CD work?

A

ATP hydroslysis drives the transport of proton against the concentration gradient from the cell to the lumen.
- Proton secretion is coupled to HCO reabsorption via HCO-Cl antiport.

44
Q

What occurs to intercalated cells of the DCT/CD under high acidosis conditions?

A

Cells express a new proton pump, HK-ATPase

- Transport via this channel is eletroneutral.

45
Q

What occurs to the proton-activated ATPase of the intercalated cells of the DCT/CD under conditions of alkalosis?

A

Proton-activated ATPase and Hco-Cl antiport switch directionality with proton-ATPAse in the basolateral membrane.

  • There are two types of intercalated cells (A and B-cells).
  • A-cells have proton channel in the luminal membrane
  • B-cells have proton channel in basolateral membrane.
  • Different cells are activated under conditions of acidosis and alkalosis.
46
Q

Where do A-type intercalated cells reside?

A

luminal membrane

47
Q

Where do B-type intercalated cells reside?

A

Basolateral membrane

Renal System (19 decks)

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