Loop of Henle, Distal Tubule and Collecting Duct Flashcards

1
Q

What are the segments of the LOH?

A
  • thin descending limb
  • thin ascending limb
  • thick ascending limb
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2
Q

What is the major function of the LOH?

A

counter current multiplication. About 25% NaCl is reabsorbed in this segment by an active transport mechanism.

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3
Q

What is the overall function of the DT?

A

regulated reabsorption of NaCl. About 5% of NaCl is reabsorbed in this segment.

DT converts TF into urine with composition distinctly different from plasma. This function is achieved by specialized and tightly regulated transport characteristics.

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4
Q

How is the composition of urine different from plasma?

A

Osmolarity: 0.2-4.0 fold of plasma

Na+: 0-2% of filtered load

K+, Ca2+, Mg2+: finely regulated

PO4 and H+: maintain pH of urine at 4.5-8.0

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5
Q

T or F. Superficial nephrons have short LOHs whereas jutamedullary nephrons have long loops.

A

T. The thin descending limb of LOH starts at the distal end of PT and runs from cortex to medulla

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6
Q

Describe the osmolarity of the fluid in the medulla

A

The fluid is markedly hyper osmotic compared 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 (from 280 at the start of the DT).

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7
Q

What is the main function of the thin descending limb?

A

concentration of TF.

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8
Q

How does the thin descending limb concentrate the TF?

A

This is achieved by the unique transport characteristics: no active transport mechanisms.

Highly water permeable (but NaCl impermeable) due to the presence of aquaporins in the epithelial membranes.

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9
Q

How does the fluid delivered to the LOH differ from plasma?

A

similar to plasma, but no protein, no organic solutes, low bicarbonate, slightly higher chloride, urea is about 6 mM.

As this flows down the thin descending limb, water is reabsorbed and the osmolarity of TF increases progressively.

TF hyperosmolarity at the tip of LOH is mainly due to NaCl, but 50-100 mOsm/L is due to urea.

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10
Q

What is the main driving force for water reabsorption in the thin descending limb?

A

Osmotic gradient between the luminal fluid and IF.

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11
Q

What aquaporins are present in the TDL?

A

AQ1 is in PT; AQ in TDL is unclear. AQ1 was thought to play role. But it is present only on long loop nephrons and not in short nephrons.

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12
Q

T or F. The structure of thin ascending limb is similar to descending limb

A

T, but the transport properties are distincly different.

It is water (and urea) impermeable due to absence of aquaporins, and high permeability to NaCl.

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13
Q

What drives NaCl reabsoprtion in the ATL?

A

As the highly concentrated TF flows upwards NaCl is reabsorbed heavily (20-25% of filtered load) due to osmotic gradient

and therefore the Osmolarity of TF decreases as it moves up.

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14
Q

T or F. At the bottom of loop there exist a urea concentration gradient between TF and IF.

A

T. As this of loop is impermeable to urea it helps maintain the osmolarity gradient.

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15
Q

How is the structure of the thick limb different from the TDL and TAL?

A

Unlike thin limbs, the thick ascending limb consists of think epithelium with lots of mitochondria in the cells

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16
Q

What is the main function of the thick limb?

A

The main function is NaCl reasbsorption that occurs by active transport mechanism.

The segment is impermeable to water.

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17
Q

What transporters are active in the thick limb?

A

1) Na-K-2Cl transporter in the luminal membrane of the epithelium. It transports 1 Na+ , 1 K+ and 2 Cl- equivalents from the lumen into cytoplasm, and therefore the transport is electro neutral. The driving force is the electrochemical gradient created by NKA.
2) Basolateral channel NKA, therefore maintains the electrochemical gradient needed for ion transport via Na-K-2Cl transporter.

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18
Q

Are there any other channels that facilitate the NaCl transport in the thick limb?

A

Yes, Apical K channel (ROMK) and BL Cl channels maintain normal steady state ionic balance

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19
Q

NK2C is sensitive to what? Why?

A

diuretics such as furosemide and bumetanide.

They have high affinity to Cl binding site and block the activity of this channel and block NaCl reabsorption.

Result is: Delivery of more NaCl and isotonic fluid into the distal segments, hyperaldosteronism, hypokalemia

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20
Q

What is the result of delivery of more NaCl and isotonic fluid into the distal segments?

A

This interferes with urine concentration causing more fluid excretion, a condition called diuresis.

These 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.

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21
Q

What endogenous hormones/substances can naturally counteract diuresis?

A

ADH may stimulate NK2C and stimulate NaCl reabsorption and cause opposing effect on diuresis.

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22
Q

How many DCT combine to a CD?

A

6-8.

NOTE: DCT and CD have distinct cell types, but the functions are soe what similar.

23
Q

How much filtered water does the DCT receive? Na, K, and Cl? Urea?

A

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

24
Q

How is Na reabsorbed in the DCT?

A

Na+ is actively transported across the epithelium causing K+ to be secreted into the lumen

25
Q

Is the amount of Na+ reabsorbed the same as the amount of K+ excreted?

A

The Na reabsorption is greater than K secretion, and therefore Cl is reabsorbed

The result is: dilution of tubular fluid, if the tubule is impermeable to water.*

26
Q

Why would the water permeability of the DCT be variable?

A

The water permeability of DCT and CD varies depending on the plasma level of ADH.

If plasma osmolarity is low due to excessive water drinking, the ADH level is low and the water permeability in DCT is low resulting in diuresis.

But, if plasma osmolarity is high due to water deprivation, the ADH level is high and water permeability in the DCT is high resulting in hyperosmotic urine.

27
Q

Two distinct transport mechanisms for Na reabsorption occur in the DCT. What are they?

A
  • Enac.

- Na-Cl co-transporter.

28
Q

How do Enacs work?

A

Na is transported by diffusion. The driving force is the electrochemical gradient, created by the NKA in the BM that imports 2K+ from the IF as 3Na+ are pumped out to the IF (Na/K ATPase).

NOTE: This channel is present in both DCT and CD.

29
Q

How do the Na-Cl co-transporters work?

A

This transports one equivalent each of Na and Cl into the epithelial cell and therefore electroneutral transport. This channel is present only in DCT.

NOTE: epithelial K+ and Cl- are pumped together to the IF to maintain gradients of each and some K+ leaks back into the tubular lumen

30
Q

What do diuretics such as amiloride and triamterene do?

A

block Enacs and, thus, block Na+ reabsorption (and K+ secretion)

31
Q

What do thiazide diuretics do?

A

block Na-Cl co-transporter to prevent Na reabsorption.

Blocking Na reabsorption results in delivery of more fluid into the distal nephron and more fluid excretion or diuresis.

32
Q

A Lumen-negative transpithelial voltage exists in the DCT and CD due to the activity of electro conductive Na channels removing positively charged Na from the tubular lumen

A

Na transport via this channel creates more negativity in the lumen causing the membrane to depolarize.

This is more in CD than DCT and plays a role in K+ secretion to both the tubules and IF.

33
Q

T or F. K secretion occurs in the DCT and CD passive diffusion through the apical K channel

A

T. The driving forces are high intracellular K concentration, and the lumen-negative potential

34
Q

Why is K secretion greater in CD than DCT?

A

due to higher depolarization in CD.

Other regulatory factors are: fluid flow – higher the fluid flow higher is K secretion.

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

35
Q

What would be the effects of loop diuretics on K secretion?

A

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

Loop diuretics deliver more Nacl and water into DCT and CD where lumen negative potential becomes higher and therefore, increase K secretion.

36
Q

What would be the effects of amiloride on K secretion?

A

Decrease K secretion. (reduce lumen-negative voltage, but slightly compensated by increased flow)

Amiloride decrease lumen negativity. Therefore no increase in K secretion.

37
Q

What would be the effects of thiazides on K secretion?

A

Thiazides: only minimal increase due to increased flow.

Thiazides block electro-neutral Na transport. Therefore, any increase in K secretion is due to increased fluid flow.

38
Q

What is aldosterone and where is it produced?

A

a mineralocorticoid secreted by the adrenal cortex

39
Q

What is the function of aldosterone?

A

It is an important regulator of Na reabsorption in the DCT and CD.

The actions of aldosterone include increased Na+ reabsorption and K+ secretion.

40
Q

Where does aldosterone act?

A

Aldosterone acts exclusively in the DCT and CD.

41
Q

How does aldosterone work?

A

It is cell permeable and binds to cytosolic and nuclear receptors and regulate gene expression related to Na reabsorption.

Aldosterone increases 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.

42
Q

What is Addison’s disease?

A

a condition where there is a complete absence of aldosterone production.

The result is increase excretion of NaCl in the urine. Nearly 2% of filtered load (500mEq/L) of NaCl is excreted in these patients (which means 6-8% is reabsorbed)

43
Q

T or F. Therefore, “Na+ reabsorption and K+ secretion do not entirely depend on aldosterone”

A

T. See last card

44
Q

What is Conn’s syndrome?

A

Conn’s syndrome is an opposite condition.

Aldosterone secreting tumors maintain a high plasma level of aldosterone. The result is increased Na reabsorption, and reduced urinary excretion of Na, which is less than 0.2% of filtered load of Na.

45
Q

What is Liddle’s syndrome?

A

Symptoms are identical to hyperaldosteronism, but plasma aldosterone is normal. AD

Aldosteronism like activity is caused by mutation of electrogenic Na channel so that it is not degraded.

46
Q

How is aldosterone secretion regulated?

A

Normally aldosterone secretion is regulated by feed back regulation.

47
Q

What conditions favor aldosterone secretion?

A
  • Reduced ECF volume and cardiac output
  • Decreased plasma Na+
  • Increased plasma K+
  • High plasma angiotensin II
  • Trauma, stress
48
Q

What conditions don’t favor aldosterone secretion?

A
  • Increased ECF volume
  • Increased plasma sodium
  • Decreased plasma K+
  • Low plasma angiotensin II
  • Low plasma ACTH levels
49
Q

What is the treatment for Liddle’s syndrome?

A

Spironolactone that targets CD Na channel not very effective treatment, but tiamterene that also targets DCT Na channel is more effective in reducing hypokalemia and hypernatremia.

50
Q

Final acidification of urine in the DCT and CD. How?

A

DCT and CD play role in H+ secretion and HCO3- reabsorption and therefore in regulation of acid-base balance.

51
Q

There are two types of cells in DCT and CD. What are they?

A
  • principal cells involved in Na reabsorption and K secretion.
  • alpha and beta intercalated cells, which play role in proton secretion and HCO absorption (or vice-versa)
52
Q

How does proton secretion occur in the DCT and CD in acidic conditions?

A

Proton secretion is some what similar to that in the PT. This is an active transport process and a different type of proton channel is involved.

In the PT NHE is involved in proton secretion to the lumen, whereas a proton pump is involved in the DT.

53
Q

What proton transporter is used in the DT?

A

the proton-activated ATPase. The ATP hydrolysis drives the transport of H+ against the concentration gradient from the cell to the lumen.

Proton secretion is coupled to HCO3- reabsorption via HCO-Cl antiport on the BL (CL- is then recycled to the interstitium and some to the lumen)

Under a condition of high acidosis, a-intercalated cells express a new proton transporter. This is HK-ATPase also known as proton pump (K+ is then recycled to the lumen)

54
Q

Under conditions of alkalosis, proton-activated ATPase and HCO3-Cl antiport swith directionality with proton-ATPAse in the basolateral membrane.

A

There are two types of intercalated cells a and b cells. A-cells have proton channel in the luminal membrane, whereas b-cells have proton channel in basolateral membrane. B cells are activated under conditions of acidosis and alkalosis.

This is just the opposite of card 54.