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Renal by Minnie: AH Version > SM 191a/192a - Functions of the Renal Tubules I and II > Flashcards

SM 191a/192a - Functions of the Renal Tubules I and II Flashcards

1
Q

What are the major functions of the loop of Henle?

A
  • Reabsorb 15-25% of filtered NaCl
  • Regulate Ca2+ and Mg2+ reabsorption
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2
Q

Are thiazide diuretics more likely to cause hypercalcemia or hypocalcemia?

Why?

A

Hypercalcemia

Inhibiting Na+ reabsorption increases Ca2+ reabsorption

  • Less Na+ reabsorbed = stronger gradient for Na+ to get into the cell
  • -> Increased activity of the Ca2+/3Na+ exchanger that gets Ca2+ out of the cell
  • -> Increased gradient for Ca2+ reabsorption through TRPV5
    • The reabsorbed Ca2+ gets pumped into the basolateral membrane through the increasec activity of the Ca2+/3Na+ exchanger mentioned above
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3
Q

Cortical or medullary collecting duct?

Reabsorbs bicarbonate

A

Cortical collecting duct

(Type A intercalated cells)

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4
Q

What are the effects of ADH on the principal cells of the cortical collecting duct?

A

Vasopressin-2 receptor is activated by ADH

  • -> increased cAMP in the cell
  • -> Movement of pre-formed aquaporins into the apical and basolateral membranes of the cortial collecting duct
    • AQP2 -> apical membrane
    • AQP3, AQP4 -> basolateral membrane
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5
Q

Which starling force dominates fluid movement from the proximal tubule to the peritubular capillary?

A

Oncotic pressure

Oncotic pressure in the peritubular capillary is high because all of the plamsa protiens are there

Fluid is sucked from the proximal tubule -> peritubular capillary

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6
Q

What is the major route of Na+ reabsorption in the distal convoluted tubule?

A
  • Apical membrane
    • Na+/Cl- contransporter (does not depend on K+)
      • Driven by high Na+ concentration in the luminal fluid
  • Basolateral membrane
    • Na+/K+ ATPase
    • Cl- channel
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7
Q

Activation of the CaSR [downregulates/upregulates] flow through the Na+/K+/2Cl- cotransporter

Explain

A

Activation of the CaSR downregulates flow through the Na+/K+/2Cl- cotransporter

This decreases the + to - gradient generated by the cotransporter that pulls Ca2+ into the interstitum, thus reducing the force that drives Ca2+ reabsorption

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8
Q

Which exogenous substances use the organic cation transport system in the proximal tubule?

A

CCCDIQV

  • cimetidine
  • ceftazidime
  • cisplatin
  • digoxin
  • indinavir
  • quinidine
  • verapamil

PCT is important for secretion of these drugs

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9
Q

Where in the kidney tubule do potassium-sparing diuretics act?

A

Cortical collecting duct

They decrease Na+ reabsorption by…

  • Directly blocking the apical Na+ channel
    • Amiloride
    • Triamterene
  • Decreasing aldosterone-stimulated Na+ reabsorption through the apical Na+ channel
    • Spironolactone
    • Eplerenone

Blocking Na+ reabsorption in the cortical collecting duct -> decreased K+ secretion

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10
Q

Cortical or medullary collecting duct?

Acid reabsorption

A

Cortical collecting duct

(Type B intercalated cells)

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11
Q

Cortical or medullary collecting duct?

Potassium secretion

A

Cortical collecting duct

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12
Q

Which diuretics target act on the distal convoluted tubule?

A

Thiazide diuretics

They block the Na+/Cl- tranpsorter in the apical epithelium

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13
Q

Why are thiazides an effective treatment for some kidney stones?

A

High Ca2+ in the urine is a common cause of kidney stones

  • Thiazides block Na+ reabsorption, which increases Ca2+ reabsorption
    • Decreased Na+ reabsorption
    • -> Increased activity of the Ca2+/3Na+ exchanger on the basolateral membrane
    • -> Increased concentration gradient for Ca2+ reabsorption through TRPV5
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14
Q

What is the most potent class of diuretics?

A

Loop diuretics

Block Na+/K+/2Cl- transporter in the thick ascending limb of the loop of Henle

Ex: Furosemide

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15
Q

Which exogenous substances use the organic anion transport system in the proximal tubule?

A

TAPPSIF

  • thiazides
  • aspirin
  • penicillin
  • probenecid
  • statins
  • ibuprofen
  • furosemide

PCT = site of secretion fo these drugs/metabolites

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16
Q

What is the driving force of Ca2+ and Mg2+ reabsorption in the thick ascending limb?

A

Electrostatic Force

  • As K+ leaks back into the lumen, it makes the lumen more positively charged
  • As Cl- leaks into the interstitium, the interstitium becomes more negatively charged
  • This creates a + to - gradient that Ca2+ and Mg2+ follow (though Claudin-16)
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17
Q

Which part of the kidney tubule secretes urea?

Which part reabsorbs it?

A

Thin descending and ascending loops of Henle secrete urea

Inner medullary collecting duct reabsorbs urea

Urea contributes to the high osmolality in the medullary collecting duct

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18
Q

How might digoxin use lead to increased beta-adrenergic signaling in a patient with heart failure?

A

Digoxin, epinephrine, and norepinephrine are secreted into the proximal tubule using the organic cation transport system

Digoxin competes with these endogenous signaling molecules, whih may (theoretically) lead to imparied excretion and secretion.

This may result in increased levels of epinephrine and norepinenphrine in the blood stream, leading to increaed beta-adrenergic activation

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19
Q

Cortical or medullary collecting duct?

Reabsorbs water in the presence of vasopressin

A

Both!

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20
Q

What endocrine factor regulates Na+ reabsorption and K+ excretion by principal cells in the cortical collecting duct?

A

Aldosterone

  • Upregulates the basolateral 3Na+/2K+ ATPase and the apical Na+ and K+ channels ->
    • Increased reabsorption of Na+
    • Increased secretion of K+
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21
Q

What is the stoichiometry of the Na+/K+ exchanger?

A

3Na+ pumped out of the cell

2K+ pumped into the cell

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22
Q

How would a defect in CaSR affect calcium homeostasis?

A

A defect in CaSR will lead to hypercalemia

Normally:

  • If Ca2+ binds to CaSR on the basolateral membrane, calcium reabsorption is downregulated
    • CaSR senses that there is enough calcium
    • Downregulates the Na+/K+/2Cl- cotransporter
    • Less Cl- moves from the lumen to the interstitum
    • Less Cl- movement = less concentration gradient to drive Ca2+ reabsorption

If there is a defect in CaSR:

  • There is no signal to downregulate the Na+/K+/2Cl- cotransporter when there is sufficient Ca2+
  • Cl- will continue to move from lumen -> interstitium
  • There remains a concentration gradient for Ca2+ reabsorption
  • Continued Ca2+ reabsorption -> hypercalcemia
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23
Q

What are the possible effects (in general) of mutations in amino acid transporters?

A

Impaired reabsorption of amino acids

(ex: inborn errors of metabolism)

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24
Q

How is the inner-medullary collecting duct similar to the cortical collecting duct?

How is it different?

A
  • Similar:
    • Na+ reabsorption pathway
    • K+ secretion pathway
    • Na+ reabsorption and K+ secretion are reciprocal
    • Water channels responsive to ADH
  • Different:
    • Medullary has ANP receptor on basolateral membrane; when bound to ANP, inhibits Na+ reabsorption
      • Promotes naturesis
    • Medullary has Urea transporter on apical membrane; reabsorbs urea, recycled back into the interstitium
      • Contributes to high interstitial osmolality
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25
Q

What is the major route of Cl- reabsorption in the cortical collecting duct?

A

None!

Cl- is not reabsorbed in the cortical collecting duct

(Na+ reabsorption is electrically offset by K+ secretion)

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26
Q

What kind of substances are reabsorbed via absorptive endocytosis in the proximal tubule?

A

Small peptides

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27
Q

What kind of epithelium is found in the proximal tubule?

A
  • Leaky (aka low-resistance)
  • Cells have microvilli to increase surface area

This allows many things to be reabsorbed

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28
Q

What is the function of a Type B intercalated cell?

What proteins facilitate this function?

A

Acid absorption, bicarbonate secretion

  • Apical
    • HCO3-/Cl- exchanger
  • Intracellular
    • Carbonic anhydrase
  • Basolateral
    • H+ ATPase (proton pump)
    • Na+/K+ ATPase
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29
Q

What is the fate of K+ that is reabsorbed in the thick ascending limb of the loop of Henle?

A

It is recycled

K+ flows out of the epithelial cells back into the lumen, so it can participate in Na+/K+/2Cl- transport again

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30
Q

Which of the following statements about calcium absorption in the distal convoluted tubule is true?

  1. Calcium reabsorption is inversely related to sodium absorption.
  2. Calcium reabsorption is blocked by thiazide diuretics.
  3. Calcium reabsorption is largely a paracellular process.
  4. Calcium reabsorption is inhibited by parathyroid hormone.
A

a. Calcium reabsorption is inversely related to sodium absorption.

When Na is reabsorbed by the distal convoluted tubule, the elevated intracellular Na concentration blunts the driving force on Na+/Ca2+ exchange in the basolateral membrane; this in turn blunts the driving force for Ca2+ entry through an apical membrane Ca2+ channel (because intracellular Ca2+ levels are higher).

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31
Q

Where in the proximal tubule epithelium is the Na+/amino acid cotransporter located?

A

Apical membrane

  • Gradient created by the Na+/K+ ATPase drives transport creates a gradient for Na+ to get back into the cell
  • Amino acids are along for the ride
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32
Q

Is the luminal fluid at the end of the loop of Henle hyertonic or hypotonic?

A

Hypotonic

H2O is secreted by the thin descending loop of Henle, but Na+ and Cl- are reabsorbed via active transport, resulting in hypotonic fluid that leaves the loop of Henle

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33
Q

Which endogenous substances use the organic anion transport system in the proximal tubule?

A

UBOC

  • Uric acid
  • Bile salts
  • Oxalate
  • cAMP

PCT = secretion of these substances

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34
Q

Cortical or medullary collecting duct?

Secretes acid

A

Cortical collecting duct

(Type A intercalated cells)

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35
Q

The __________ is the primary location for secretion of drugs and drug metabolites

A

The Proximal Convoluted Tubule is the primary location for secretion of drugs and drug metabolites

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36
Q

In the thick ascending limb, Ca2+ and Mg2+ are reabsorbed [paracellularly/transcellularly]

A

In the thick ascending limb, Ca2+ and Mg2+ are reabsorbed paracellularly

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37
Q

Where in the proximal tubule epithelium is the Na+/phosphate cotransporter located?

A

Apical membrane

  • Gradient created by the Na+/K+ ATPase drives transport creates a gradient for Na+ to get back into the cell
  • Phosphate is along for the ride
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38
Q

In which nephron segments do you find the electroneutral, thiazide-sensitive, sodium- chloride co-transporter?

A

Distal convoluted tubule

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39
Q

Which endogenous substances use the organic cation transport system in the proximal tubule?

A

END-CSH

  • epinephrine
  • norepinephrine
  • dopamine
  • creatinine
  • serotonin
  • histamine

PCT = Secretion of these substances

40
Q

Bivalent cations (Mg2+ and Ca2+) are reabsorbed either paracellularly or transcellularly

In which parts of the kidney tubule does each type of transport occur?

A
  • *Paracellular** reabsorption of Mg2+ and Ca2+ occurs in the
  • *Loop of Henle**
  • *Transcellular** reabsorption of Mg2+ and Ca2+ occurs in the
  • *Distal Convoluted Tubule**
41
Q

If a patient has a high acid load, would it be adaptive to increase Type A Intercalated Cells or Type B Intercalated Cells?

A

Increase Type A intercalated cells

Secrete acid, reabsorb bicarbonate -> Neutralize acid load

42
Q

Cortical or medullary collecting duct?

Chloride reabsorption

A

Medullary collecting duct

43
Q

Cortical or medullary collecting duct?

Na+ reabsorption

44
Q

Which of the following statements about the Loop of Henle is FALSE?

  1. The Loop of Henle contains the transporter targeted by loop diuretics.
  2. The luminal fluid at the end of the Loop of Henle is hypotonic.
  3. The descending limb is water impermeable.
  4. Bartter’s syndrome is an inherited disorder of the thick ascending limb.
A

c. The descending limb is water impermeable.

45
Q

Carbonic anhydrase inhibitors will evoke which of the following changes in proximal tubular solute reabsorption?

  1. Diminished Na+ reabsorption by the Na-proton exchanger
  2. Elevation in Na-bicarbonate efflux from the cell on the interstitial side
  3. Diminished reclaimation of bicarbonate
  4. Increased generation of cytosolic carbonic acid
  5. Decreased generation of tubular fluid carbonic acid
A

c. Diminished reclaimation of bicarbonate

46
Q

Describe the histology of the distal convoluted tubule cells

A

Thick walled

Filled with mitochondria => lots of active transport

47
Q

What is the function of a Type A intercalated cell?

Which proteins facilitate this function?

A

Acid secretion, Bicarbonate reabsorption

  • Apical
    • H+ ATPase (proton pump) secretes protons
    • H+/K+ ATPase pumps protons out and K+ in
  • Intracellular
    • Carbonic Anhydrase
  • Basolateral
    • Na+/K+ ATPase
    • HCO3-/CL- exchanger
48
Q

Where in the kidney tubule does furosemide act?

What is its mechanism of action?

A

Thick ascending limb of the loop of Henle

Blocks the Na+/K+/2Cl- transporter

49
Q

In which of the following nephron segments do you find the epithelium with the highest electrical resistance?

a. Proximal tubule
b. Descending limb of loop of Henle
c. Ascending thick limb of loop of Henle
d. Distal convoluted tubule
e. Cortical collecting duct

A

e. Cortical collecting duct

50
Q

Competition for which transport protein leads to many drug-drug interactions?

A

P-gp

In the proximal convoluted tubule
(the primary site of secretion for drugs and drug metabolites)

51
Q

Cortical or medullary collecting duct?

Secretes bicarbonate

A

Cortical collecting duct

(Type B intercalated cells)

52
Q

Where in the proximal tubule epithelium is the Na+/H+ exchanger located?

A

Apical membrane

Na+: lumen -> cell

H+: cell -> lumen

Driven by Na+ gradient created by the Na+/K+ ATPase

53
Q

What are the major functions of the principal cells of the cortical collecting duct?

A
  • Na+ reabsorption
  • K+ secretion
  • H2O reabsorption in the presence of vasopressin
54
Q

In the distal convoluted tubule, how are Na+ reabsorption and Ca2+ reabsorption related?

A

They are opposite

  • Decreased Na+ reabsorption -> increased Ca2+ reabsorption
    • Less Na+ reabsorbed = stronger gradient for Na+ to get into the cell
    • -> Increased activity of the Ca2+/3Na+ exchanger that gets Ca2+ out of the cell
    • -> Increased gradient for Ca2+ reabsorption through TRPV5
  • Increased Na+ reabsorption -> decreased Ca2+ reabsorption
    • Opposite of above
55
Q

Where in the proximal tubule epithelium is the Na+/K+ ATPase located?

A

Basolateral membrane

3Na+: cell -> interstitium

2K+: interstitium -> cell

56
Q

Which parts of the kidney tubule are involved in fine tuning Na+ reabsorption?

A

Distal convoluted tubule

Collecting duct

57
Q

Where in the kidney tubule does transcellular Ca2+ reabsorption occur?

Through which protein?

A

Distal covoluted tubule

  • Apical
    • TRPV5 channel
  • Basolateral
    • Ca2+/3Na+ exchanger
      • Driven by Na+ gradient into the cell
58
Q

Which cross-section shows the thick ascending limb?

Which shows the the thin ascending limb?

How do you know?

A

A = thick ascending limb - lots of mitochondria and thicker

B = thin ascending limb

59
Q

Which sections of the kidney tubule are permeable to water in the presence of ADH?

A

Proximal tubule

Thin descending limb of the loop of Henle

Collecting duct (cortical and medullary)

60
Q

Which of the following statements is NOT true about the proximal tubule?

  1. 90% of filtered bicarbonate is reclaimed
  2. Approximately 65-70% of total filtered sodium is reabsorbed
  3. Glucose reabsorption is near complete under all conditions
  4. Organic anion secretion can be blocked by probenecid
  5. The apical membrane contains numerous microvilli
A

c. Glucose reabsorption is near complete under all conditions

61
Q

How does sickle-cell anemia cause damage to the nephron?

A
  • When the peritubular capillaries run antiparallel to the thick ascending limb of the loop of Henle, solutes move into the capillary
  • This increases the tonicity of the blood in the peritubular capillary, resulting in slight shrivelling of RBCs
  • Normally, the RBCs re-hydrate as water moves into the capillary when it runs antiparallel to the thin descening limb
  • In sickle cell disease, the shrivelling of RBCs results in sickling, which can damage the peritubular capillaries
  • This decreases the maximal concentrating ability of the kidney (Reduced ability to reabsorb water)
62
Q

Describe the role of urea in establishment of the countercurrent multiplier

A
  • Urea is reabsorbed in the medullary collecting duct via urea transporters
  • Most of the urea hangs out in the medulla, contributing to its high osmolality
    • This increases the concentrating ability of the kidney (Can reabsorb more water in the cortical collecting duct if vasopressin is present)
  • Some of the urea is secreted into the thin loop of Henle
    • This urea may be re-absorbed in the medullary collecting duct
63
Q

Which transport proteins are important for organic anion transport in the proximal tubule?

Where are they located?

A

Organic anions are primarily secreted in the proximal tubule

  • Basolateral
    • SLC13A3
    • OAT1
    • OAT3
  • Apical
    • MRP3
    • MRP4
    • ABCG2
64
Q

Why would SGLT2 inhibitors be therapeutic for patients with diabetes?

A
  • SGLT2 is a transport protein that moves glucose from the proximal tubule into the epithelium, so it can be reabsorbed into the bloodstream
  • Inhibiting SGLT2 would inhibit the reabsorption of glucose, therefore lowering blood glucose levels
65
Q

What is the major route of Na+ reabsorption in the cortical collecting duct?

A

In principal cells of the cortical collecting duct

  • Apical
    • Na+ selective channel w/high open probability
      • Target of amiloride
      • Remains electrically neurtral due to K+ secretion
  • Basolateral
    • 3Na+/2K+ ATPase
66
Q

Which amino acid transporters are important for amino acid reabsorption?

Where are they located?

A
  • Apical
    • Na+/Amino Acid cotransporter
      • Driven by Na+ gradient into the cell, created by the Na+/K+ ATPase
    • Amino acid transporter
  • Basolateral
    • Amino acid transporter
67
Q

Where in the kidney tubule is Mg2+ reabsorbed?

Through which protein?

A

Distal convluted tubule

  • Apical
    • TRPM6
  • Basolateral
    • Nobody knows!
68
Q

Describe the process of ammonium secretion in the proximal tubule.

Why is this important?

A
  • Glutamine -> NH3 + glutamate
    • Ammonia is generated from the breakdown of glutamine in the proximal tubule epithelial cell.
    • Catalyzed by glutaminase
  • NH3 diffuses out of the cell
  • NH3 + H+ -> NH4+
    • H+ in the lumen comes from Na+/H+ exchanger
    • Trapped by binding to NH3
  • NH4+ is stuck in the lumen
    • Charged particles cannot diffuse
  • This is important for excreting H+ and preventing acidemia
69
Q

Which renal tubule cross sections do you see in the inner medulla?

A

Collecting duct

Thin descending and ascending limbs of long loops of Henle

70
Q

What is the “transport maximum” for bicarbonate?

What happens if plasma concentration exceeds this maximum

A

~26 mEq/L

If plasma concentration exceeds this level, bicarbonate will be excreted in the urine

71
Q

What are the effects of aldosterone binding to its cytoplasmic receptor?

A

Aldoserone/receptor complex is transported to the nucleus

  • Acts as a transcription factor
    • More Na+/K+ ATPases
    • More ENaC (Na+ channels)
    • More ROMK (K+ channels)
  • -> increased Na+ reabsorption, K+ secretion via…
    • Short-term mechanisms
      • Increased SGK1 activity -> phosphorylates NEDD-2
      • P-NEDD-2 cannot retrieve ENaC from the membrane
      • => More ENaC to reabsorb Na+
    • Later mechanisms
      • Increased surface area of basolateral membranes
      • -> Inreased Na+/K+ ATPase activity
72
Q

Describe the histology of the proximal convoluted tubule cells

A

Thick brush border made from microvilli

The PCT is responsible for absorbing a ton of stuff

73
Q

Describe the establishment of the countercurrent multiplier

A
  1. Thick Ascending Limb of the Loop of Henle:
    Active transport of NaCl from tubule -> interstitium
    Via: Na+/K+ ATPase, Cl- uniporter
    Water cannot follow becuase the TAL is impermeable
  2. Thin Descending Limb of the Loop of Henle:
    Reabsorption of H2O along the osmolality gradient established in step 1
    Thin Descending Limb is permeable to H2O
  3. High osmolality in the inner medulla helps extract water from the collecting duct
    If vasopressin (ADH) is present
  4. Urea is reabsorbed in the collecting duct, which contributes to the high osmolality in the medulla. It is secreted into the thin loop of Henle and recycled
  5. Peritubular capillaries flow anti-parallel to the loop of Henle (and parallel to the collecting duct)
    They absorb some of the solutes pumped out of the TAL
    They absorb a lot of water pumped out by the TDL - this helps to maintain the high osmolality in the medulla
74
Q

In the inner medullary collecting duct…

Binding of ADH to its receptor increases c_MP, which…

Binding of ANP to its receptor increases c_MP, which…

A

Binding of ADH to its receptor increases c_A_MP, which _promotes the insertion of aquaporins into the apical and basolateral membranes_

Binding of ANP to its receptor increases cGMP, which, blocks reabsorption of Na+ through ENaC

75
Q

In which nephron segments will aldosterone regulate sodium reabsorption?

A

Cortical collecting duct

(Principal cells)

76
Q

The Loop of Henle reabsorbs ____% to ______% of filtered NaCl

A

The Loop of Henle reabsorbs 15% to 25% of filtered NaCl

77
Q

Where in the kidney tubule do thiazide diuretics act? Which transporter do they target?

A
  • Distal convoluted tubule
  • Target the Na+/Cl- cotransporter on the apical membrane
78
Q

What are the physiologic triggers for aldosterone secretion?

A
  • Increased Angiotensin II
    • Angiotensin II increases via RAAs in response to…
      • Low blood volume
      • Decreased Na+ delivery to the macula densa
  • Increased blood K+ levels
79
Q

Describe the process of bicarbonate reclamation in the proximal tubule

A
  • HCO3- + H+ -> H2CO3 (Carbonic acid)
  • Carbonic acid -> H2O + CO2 by carbonic anhydrase
  • H2O and CO2 diffuse into the epithelium
  • Carbonic anhydrase re-synthesizes carbonic acid from H2O and CO2
  • Carbonic acid -> H+ and HCO3-
  • H+ is pumped back into the lumen via Na+/H+ exchanger
  • HCO3- moves into the interstitium via Na+/3HCO3- co-transporter
80
Q

Which sections of the kidney tubule are responsible for reabsorbing water to concentrate urine?

A
  • Proximal tubule
  • Thin descending loop of Henle
    • H2O reabsorption relies on the osmolality gradient established by the countercurrent multiplier
  • Collecting tubule
    • Only permeable to H2O if ADH is present
    • Also relies on onsmolality gradient
81
Q

What are the unique histologic features of the cortical collecting duct?

A
  • Points of union of adjacent collecting ducts
  • Cellular heterogeneity
    • Principal cells - Sodium reabsorption
    • Intercalated cells
      • Type A - Acid secretion and Bicarb reabsorption
      • Type B - Bicarb secretion and Acid reabsorption
  • Tight epithelium (high resistance)
82
Q

Which sodium transporters are located on the apical side of the proximal tubule epithelium?

Which are located on the basolateral side?

A
  • Apical
    • Na+/H+ exchanger
    • Na+/[solute] cotransporter
      • Glucose
      • Amino acids
      • Phosphate
  • Basolateral
    • Active transport mechanisms! Create a gradient for Na+ reabsorption from the lumen, and other solutes come too
      • Na+/K+ ATPase
      • Na+/3HCO3- cotransporter
83
Q

Cortical or medullary collecting duct?

Reabsorbs urea

A

Medullary collecting duct

84
Q

Which section of the kidney tubule contains the macula densa?

A

Thick ascending limb of the loop of Henle

85
Q

At the level of the proximal convoluted tubule, why is hydrostatic pressure lower in the peritubular capillaries than in the glomerular capillaries?

A

Constriction of the efferent arteriole

  • Raises hydrostatic pressure in the glomerulus
    • Increased flomerular filtration
    • -> increased oncotic pressure in the peritubular capillaries
  • Leads to lower hydrostatic pressure in the peritubular capillaries

Lower hydrostatic pressure + increased oncotic pressure = reabsorption

86
Q

An 84 year old woman developed recurrent “heartburn” that she self-medicated with an over-the- counter medication (cimetidine). One week later, her serum creatinine level of 2.7 mg/dl (increased from 1.8 mg/dl). Her physician is very concerned about rapid progression of her underlying renal disease, but is also suspicious that the serum creatinine elevation may have been caused by cimetidine.

Why does the physician suspect cimetidine?

A

Cimetidine is secreted into the urine in the proximal convoluted tubule using the organic cation transport system

Creatinine is also secreted into the urine using this system

The two substances compete for these tranporters; if Cimetidine is present, it could block creatinine secretion in the PCT, leading to increased serum creatinine

87
Q

Where in the proximal tubule epithelium is the Na+/Glucose cotransporter located?

Which solute is driving transport?

A

Apical membrane

Na+ movement drives the transporter

  • Na+/K+ ATPase in the basolateral membrane pumps Na+ out of the cell, into the interstitium
  • This creates a concentration gradient that pulls Na+ from the lumen into the PCT cell
  • Glucose comes along for the ride
88
Q

Which sections of the kidney tubule are permeable to water in the absence of ADH?

A

Proximal tubule

Thin descending limb of the loop of Henle

89
Q

Is the thick ascending limb of the loop of Henle permeable to water?

90
Q

How can reabsorption in the proximal tubule be isosmotic?

(If it was isosmotic, wouldn’t there be no driving force for fluid movement?)

A

Active transport of Na+ creates local osmotic gradients for water reabsorption

  • Na+ reabsorption is very important for this
    • Apical membrane
      • Na+/H+ exchanger
    • Basolateral membrane
      • Na+/K+ exchanger
      • Na+/HCO3- cotransporter
    • Paracellular transport
91
Q

Which transport proteins are important for the reabsorption of glucose?

Where are they located?

A
  • Apical Membrane
    • SGLT2 (Na+/Glucose cotransporter)
      • Gradient favoring Na+ movement into the cell is created by the Na+/K+ ATPase
  • Basolateral membrane
    • Na+/K+ ATPase
      • Pumps Na+ out through the basolateral membrane, creating an concentration gradient that promotes Na+ movement into the cell
    • Glucose transporter
92
Q

How would inhibition of gluitaminase in the proximal convoluted tubule affect the acid/base balance in the serum?

A

When glutaminase is active:

  • glutamine -> NH3 + glutamate
  • NH3 is secreted into the lumen
  • NH3 + H+ -> NH4+
    • This traps H+ in the lumen, allowing it to be secreted
      ​

Inhibition of gluitaminase:

  • No NH3 is generated and secreted
  • Fewer things to bind to and trap H+ in the urine, so it is reabsorbed
    • HCO3- still binds H+ in the PCT
    • B-intercaleated cells in the collecting duct may reabsorb H+
  • Buildup of H+ and possible acidemia

This is a theoretical question, I’m not sure if anything actually inhibits gluitaminase

93
Q

What is the function of intercalated cells of the cortical collection duct?

A

Manage acid and base secretion and reabsorptin

  • Type A intercalated cells: Active when the serum is acidic
    • Secrete acid
    • Reabsorb bicarbonate
  • Type B intercalated cells: Active when the serum is alkaline
    • Secrete bicarbonate
    • Reabsorb acid
94
Q

Which section of the kidney is responsive to Atrial Natriuretic Peptide (ANP)?

What is the response?

A

Inner medullary collecting duct

  • ANP is secreted in response to increased blood volume in the right atrium
  • ANP binding to its receptor in the inner medullary collecting duct initiates natriuresis
    • ​Increases cGMP
      • Blocks the ENaC channel on the apical membrane
  • > decreased Na+ reabsorption
    * This also results in decreased K+ secretion through ROMK
95
Q

Which transport proteins are important for organic cation transport in the proximal tubule?

Where are they located?

A

PCT = organic cation secretion

  • Basolateral
    • OCT2/3
  • Apical
    • P-gp
    • MRP-2
96
Q

In Liddle syndrome, activating mutations of the epithelial sodium channel located in the apical membrane of cortical collecting duct principal cells leads to aldosterone-independent sodium reabsorption, volume expansion and hypertension.

Which of the following treatment strategies should be most effective in this disorder?

a) Furosemide (a loop diuretic)
b) Amiloride (a potassium-sparing diuretic)
c) Acetazolamide (a carbonic anhydrase inhibitor)
d) Cortisone (a glucocorticoid)

A

b) Amiloride (a potassium-sparing diuretic)

Amiloride blocks this specific Na+ channel in the principal cells of the cortical collecting duct, thus reversing the defect

97
Q

What is Dent disease?

What causes it?

A

Dent disease is a defect in endosomal acidification that leads to low molecular-weight proteinuria

It is caused by a mutation in the proximal tubule Cl- channel gene CLCN5

Renal by Minnie: AH Version (27 decks)

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