Diuretic Agents

Question 1

What is the first segment of the nephron after the glomerulus?

Answer 1

The proximal tubule (specifically, the proximal convoluted tubule or PCT).

Question 2

What are some key substances reabsorbed in the early proximal tubule?

Answer 2

Sodium bicarbonate (NaHCO₃), sodium chloride (NaCl), glucose, amino acids, and other organic solutes.

Question 3

Through what mechanism are glucose and amino acids reabsorbed in the proximal tubule?

Answer 3

Via specific transport proteins on renal tubule cells.

Question 4

How is potassium (K⁺) reabsorbed in the proximal tubule?

Answer 4

Via the paracellular pathway—between cells through tight junctions.

Question 5

What drives the passive reabsorption of potassium in the proximal tubule?

Answer 5

Electrical gradients and solvent drag caused by reabsorption of other ions and water.

Question 6

How is water reabsorbed in the proximal tubule?

Answer 6

Passively, by osmosis, following solutes.

Question 7

What happens to the osmolality of fluid in the proximal tubule as water and solutes are reabsorbed?

Answer 7

It remains nearly constant (around 300 mOsm/kg), similar to plasma.

Question 8

What is inulin, and why is it used in renal studies?

Answer 8

Inulin is an experimental marker that is filtered at the glomerulus but neither reabsorbed nor secreted; it stays in the tubule and helps track reabsorption of other solutes.

Question 9

What happens to the concentration of inulin in the tubular fluid as reabsorption occurs?

Answer 9

It increases because water is reabsorbed and inulin remains in the tubule.

Question 10

Why do the concentrations of solutes like glucose and Na⁺ decrease relative to inulin?

Answer 10

Because they are reabsorbed, while inulin is not.

Question 11

What percentage of filtered sodium (Na⁺) is reabsorbed in the proximal tubule?

Answer 11

About 66%.

Question 12

What percentage of filtered bicarbonate (NaHCO₃) is reabsorbed in the proximal tubule?

Answer 12

About 85%.

Question 13

What percentage of filtered potassium (K⁺) is reabsorbed in the proximal tubule?

Answer 13

About 65%.

Question 14

What percentage of filtered water is reabsorbed in the proximal tubule?

Answer 14

About 60%.

Question 15

What percentage of filtered glucose and amino acids is reabsorbed in the proximal tubule?

Answer 15

Virtually 100%.

Question 16

Which ion’s reabsorption drives much of the transport of other substances in the proximal tubule?

Answer 16

Sodium (Na⁺).

Question 17

Why does water follow solutes in the proximal tubule?

Answer 17

Due to osmotic gradients created by solute reabsorption.

Question 18

Which group of diuretics primarily acts in the proximal tubule?

Answer 18

Carbonic anhydrase inhibitors (e.g., acetazolamide)

Question 19

What do carbonic anhydrase inhibitors block in the proximal tubule?

Answer 19

They block the reabsorption of sodium bicarbonate (NaHCO₃)

Question 20

Which two solutes in the proximal tubule are most relevant for diuretic action?

Answer 20

Sodium bicarbonate (NaHCO₃) and sodium chloride (NaCl)

Question 21

Why is the proximal tubule a powerful target for potential diuretics?

Answer 21

Because it reabsorbs a large amount of NaCl; blocking this could cause strong diuresis

Question 22

Which investigational drugs may block NaCl reabsorption in the proximal tubule?

Answer 22

Adenosine receptor antagonists

Question 23

What transporter begins the process of sodium bicarbonate reabsorption in the proximal tubule?

Answer 23

Na⁺/H⁺ exchanger (NHE3) in the luminal membrane

Question 24

What does the Na⁺/H⁺ exchanger do?

Answer 24

It allows Na⁺ to enter the PCT cell from the tubule and secretes H⁺ into the lumen

Question 25

What happens to the H⁺ secreted into the tubular lumen?

Answer 25

It combines with bicarbonate (HCO₃⁻) to form carbonic acid (H₂CO₃)

Question 26

Which enzyme converts carbonic acid (H₂CO₃) into CO₂ and H₂O?

Answer 26

Carbonic anhydrase (in the tubular fluid)

Question 27

How does CO₂ enter the proximal tubule cell?

Answer 27

By simple diffusion (it’s a gas)

Question 28

What happens to CO₂ once it enters the proximal tubule cell?

Answer 28

It is converted back into carbonic acid (H₂CO₃) by intracellular carbonic anhydrase

Question 29

What does H₂CO₃ inside the cell split into?

Answer 29

H⁺ and HCO₃⁻

Question 30

What happens to the H⁺ formed inside the proximal tubule cell?

Answer 30

It is secreted back into the lumen by the Na⁺/H⁺ exchanger

Question 31

What happens to the HCO₃⁻ formed inside the proximal tubule cell?

Answer 31

It is transported into the blood via a basolateral membrane transporter

Question 32

Which enzyme is essential for bicarbonate reabsorption in the proximal tubule?

Answer 32

Carbonic anhydrase

Question 33

What happens if carbonic anhydrase is inhibited?

Answer 33

Bicarbonate cannot be reabsorbed, leading to its loss in urine

Question 34

What effect does blocking bicarbonate reabsorption have on fluid balance?

Answer 34

It increases urine output (diuresis), as water follows bicarbonate

Question 35

What kind of urine is produced by carbonic anhydrase inhibitors?

Answer 35

Alkaline urine (because of bicarbonate loss)

Question 36

What condition can result from the bicarbonate loss caused by carbonic anhydrase inhibitors?

Answer 36

Metabolic acidosis

Question 37

Which basolateral pump maintains a low intracellular Na⁺ concentration in the proximal tubule cell?

Answer 37

Na⁺/K⁺-ATPase

Question 38

How does blocking carbonic anhydrase affect both HCO₃⁻ and Na⁺ reabsorption?

Answer 38

It disrupts the Na⁺/H⁺ exchanger cycle, reducing both bicarbonate and sodium reabsorption

Question 39

What triggers the release of adenosine in the body?

Answer 39

Adenosine is released when there is low oxygen (hypoxia) and high ATP consumption (energy use).

Question 40

How many types of receptors does adenosine act on?

Answer 40

Adenosine acts on four receptors: A₁, A₂A, A₂B, and A₃.

Question 41

What effect does adenosine have on the kidney’s filtration rate (GFR)?

Answer 41

Adenosine reduces GFR to lower the kidney’s energy usage

Question 42

What is the effect of adenosine on sodium reabsorption in the proximal tubule?

Answer 42

It increases sodium (Na⁺) reabsorption by stimulating the NHE3 transporter.

Question 43

What is NHE3 and where is it located?

Answer 43

NHE3 is the sodium-hydrogen exchanger 3; it’s located on the apical membrane of proximal tubule cells.

Question 44

How does NHE3 function in sodium reabsorption?

Answer 44

NHE3 brings Na⁺ into the pt cell from the tubular fluid in exchange for H⁺ going out.

Question 45

What are adenosine A₁ receptor antagonists?

Answer 45

They are drugs that block the A₁ receptor to stop adenosine’s actions.

Question 46

How do A₁ antagonists affect sodium handling in the proximal tubule?

Answer 46

They reduce NHE3 activity, which leads to less sodium reabsorption.

Question 47

What is the effect of A₁ antagonists on the collecting duct?

Answer 47

They also reduce NaCl reabsorption in the collecting duct.

Question 48

What overall effect do A₁ antagonists have on urine?

Answer 48

They increase sodium and water loss in the urine (diuretic effect).

Question 49

How do A₁ antagonists affect the kidney’s blood vessels?

Answer 49

They have vasomotor effects — they alter blood flow in the kidney’s microvasculature.

Question 50

What happens to bicarbonate and organic solutes in the late proximal tubule?

Answer 50

They have mostly been reabsorbed by this point.

Question 51

What is the composition of the luminal fluid in the late proximal tubule?

Answer 51

It contains mostly sodium (Na⁺) and chloride (Cl⁻).

Question 52

Does sodium reabsorption continue in the late proximal tubule?

Answer 52

Yes, sodium reabsorption continues.

Question 53

How does sodium continue to be reabsorbed?

Answer 53

Through the Na⁺/H⁺ exchanger (NHE3), which swaps Na⁺ into the cell and H⁺ out into the lumen.

Question 54

What happens to the secreted H⁺ in the absence of bicarbonate?

Answer 54

It accumulates in the lumen as free H⁺, since there’s no HCO₃⁻ left to bind with.

Question 55

What is the effect of free H⁺ in the tubular lumen?

Answer 55

It causes the luminal pH to drop (acidification).

Question 56

What does the drop in luminal pH due to accumulation of free H+ activate?

Answer 56

Cl⁻/base exchanger.

Question 57

What does the Cl⁻/base exchanger do?

Answer 57

It reabsorbs chloride (Cl⁻) in exchange for a base.

Question 58

What is the net effect of Na⁺/H⁺ and Cl⁻/base exchangers working together?

Answer 58

The combined reabsorption of sodium and chloride (NaCl).

Question 59

How is water reabsorbed in the PCT?

Answer 59

Water is reabsorbed due to osmotic forces created by solute reabsorption.

Question 60

What happens to luminal fluid osmolality in the PCT?

Answer 60

Osmolality remains nearly constant because water and solutes are reabsorbed together.

Question 61

What happens to inulin in the PCT?

Answer 61

Inulin becomes more concentrated as water is reabsorbed.

Question 62

How does mannitol affect water reabsorption?

Answer 62

Mannitol increases in concentration, preventing further water reabsorption.

Question 63

What effect does mannitol have on urine formation?

Answer 63

Mannitol prevents water reabsorption, leading to increased urine production.

Question 64

Organic acid secretory systems are found in which part of the proximal tubule?

Answer 64

Middle third of the straight part (S2 segment).

Question 65

What do organic acid secretory systems secrete?

Answer 65

They secrete organic acids like uric acid, NSAIDs, diuretics, and antibiotics.

Question 66

Where do organic acids get secreted into?

Answer 66

Into the luminal fluid from the blood.

Question 67

What is the role of organic acid secretory systems in drug action?

Answer 67

They help deliver diuretics to the luminal side of the tubule where they act.

Question 68

Where are organic base secretory systems located?

Answer 68

In the early (S1) and middle (S2) segments of the proximal tubule.

Question 69

What do organic base secretory systems secrete?

Answer 69

They secrete organic bases like creatinine and choline.

Question 70

What part of the nephron does the proximal tubule empty into?

Answer 70

The thin descending limb of Henle’s loop.

Question 71

Where does the proximal tubule connect to the loop of Henle?

Answer 71

At the boundary between the inner and outer stripes of the outer medulla.

Question 72

What is the function of the thin descending limb?

Answer 72

It allows water to be reabsorbed due to osmotic forces.

Question 73

Why is water pulled out from the descending limb?

Answer 73

Because of the hypertonic medullary interstitium.

Question 74

What is meant by "hypertonic medullary interstitium"?

Answer 74

It is the surrounding tissue with a high concentration of solutes.

Question 75

What drives water reabsorption in the descending limb?

Answer 75

Osmosis due to the solute gradient outside the tubule.

Question 76

Explain What are impermeant luminal solutes?

Answer 76

Solutes that cannot cross the tubular wall to leave the tubule.

Question 77

What effect do impermeant solutes like mannitol have on water reabsorption?

Answer 77

They oppose water reabsorption by holding water inside the tubule.

Question 78

What is aquaretic activity?

Answer 78

The ability of a substance to promote water excretion.

Question 79

How does mannitol exhibit aquaretic activity?

Answer 79

By staying in the tubule and preventing water reabsorption.

Question 80

What happens in the thin ascending limb of Henle’s loop?

Answer 80

It is impermeable to water but permeable to some solutes.

Question 81

Can water be reabsorbed in the thin ascending limb?

Answer 81

No, water cannot leave this segment.

Question 82

Can solutes move out in the thin ascending limb?

Answer 82

Yes, solutes like Na⁺ and Cl⁻ can be reabsorbed.

Question 83

Why is the difference in permeability between descending and ascending limbs important?

Answer 83

It helps the kidney concentrate or dilute urine effectively.

Question 84

What part of the nephron comes after the thin limb of Henle's loop?

Answer 84

The thick ascending limb (TAL).

Question 85

How much of the filtered sodium is reabsorbed in the TAL?

Answer 85

About 25%.

Question 86

Is the thick ascending limb permeable to water?

Answer 86

No, it is nearly impermeable to water.

Question 87

How is sodium reabsorbed in the TAL?

Answer 87

It is actively reabsorbed from the lumen.

Question 88

What happens to tubular fluid in the TAL due to salt reabsorption without water?

Answer 88

It becomes diluted.

Question 89

What is the TAL also called due to its function?

Answer 89

The diluting segment.

Question 90

Why is the TAL called the diluting segment?

Answer 90

Because it removes salt without removing water, diluting the tubular fluid.

Question 91

What effect does the TAL have on the medullary interstitium?

Answer 91

It increases medullary hypertonicity.

Question 92

Why is medullary hypertonicity important?

Answer 92

It helps the collecting duct concentrate urine.

Question 93

Does water follow salt in the TAL like in the proximal tubule?

Answer 93

No, because the TAL is water-impermeable.

Question 94

How does the TAL help in urine concentration indirectly?

Answer 94

By making the medulla hypertonic, which aids water reabsorption in the collecting duct.