Renal Transport Mechanisms Flashcards

1
Q
  • What five barriers must a substance cross to be reabsorbed?
A
  • Luminal cell membrane
  • Cytosol
  • Basolateral cell membrane
  • Interstitial fluid
  • Capillary wall
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2
Q
  • Why do we filter so much only to reabsorb 99%?
A
  • Foreign substances are filtered into the tubule
    • Certain substances are secreted into the filtrate (toxic in high concentration)
  • FIltering ions and water into the tubule makes regulation simple
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3
Q
  • What things are reabsorbed (and at what percentages) in the proximal convuluted tubule?
A
  • Glucose-100%
  • Amino Acids-100%
  • Urea-50%
  • Sodium-65-70%
  • Water-65-70%
  • Potassium-70%
  • Phosphate-70%
  • Calcium-70%
  • Magnesium-30%
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4
Q
  • What things are reabsorbed (and at what percentages) in the proximal straight tubule?
A
  • Phosphate-15%
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5
Q
  • What is reabsorbed (and at what percentages) in the thick ascending LOH?
A
  • Sodium-25%
  • Potassium-20%
  • Calcium-25%
  • Magnesium-60%
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6
Q
  • What things are reabsorbed (and at what percentages) in the Distal Convuluted Tubule?
A
  • Sodium-5%
  • Calcium-8%
  • Magnesium-5%
  • H20 and urea-variable
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7
Q
  • What things are reabsorbed (and at what percentages) in the collecting duct?
A
  • Sodium-3%
  • Water and urea-variable
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8
Q
  • What is the “workhorse” of the PCT? Where is it located?
A
  • Na+/K+ ATPase
  • Basolateral membrane
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9
Q
  • What are the two ways by which a substance can be transported across the tubule lumen and into the interstitial space?
A

Transcellular (thru the cell)

Paracellular (between the cell)

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10
Q
  • What types of channels are found on the apical surface of the proximal convuluted tubule?
A
  • Sodium leak channels (majority of Na+ reabsorption)
  • Na+/H+ exchanger (antiporter)
  • Aquaporin Is
  • SGLT I and 2
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11
Q
  • How does the Na+/H+ exchanger (NHE3) work?
A
  • Pumps a Na+ in and a H+ ion out
  • H+ combines with HCO3- in the tubular lumen via CA- H2CO3 then dissociates into H2O and CO2
  • H2O can get into the cell via AQP1s
  • CO2 diffuses into the cell
  • CO2 and H2O combine again to form H2CO3 which spontaneously dissociates into H+ and HCO3-
  • HCO3- is transported into the interstitial fluid via transporter
  • H+ goes back into tubular lumen via Na+/H+ exchanger
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12
Q

What are the two important consequences of the Na+/H+ exchanger?

A
  • Sodium reabsorption
  • Bicarbonate reabsorption
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13
Q
  • How does chloride reabsorption in the proximal tubule work?
A
  • Early in the proximal tubule, a lot of water (compared to Cl-) is reabsorbed
    • Leads to an increase in Cl- conc in the lumen
  • Later segement of the proximal tubule-Na+ and H2O have been reabsorbed, Cl- concentration has increased by 20%
  • Provides a chemical gradient that drives chloride movement passively along paracellular pathway down its concentration gradient
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14
Q
  • Where in the proximal tubule are the SGLT 2 and SGLT 1 located? What side of the membrane are they on? What type of transporter are they?
  • Which is most responsible for reabsorption of glucose
A
  • SGLT 2 is located on the apical side of the first and second segments of the proximal tubule
  • SGLT 1 is located on the apical side of the third segement of the proximal tubule
  • Both are symporters (transporting Na+ and glucose in the same direction-into the cell)
  • SGLT 2 responsible for 90% glucose reabsorption
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15
Q
  • Which of the SGLT transporters has high affinity and low capacity?
  • Which of the SGLT transporters has low affinity and high capacity?
A

SGLT 1 and GLUT 1

SGLT 2 and GLUT2

*High affinity rewuires only a lower concentration to fill binding sites*

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16
Q
  • What is the transport maximum for glucose?
  • What happens beyond this point?
A
  • When all SGLT1 and SGLT2 receptor sites are occupied
  • 375 mg/min (Plasma glucose level of 200)
  • No more glucose can be reabsorbed and is excreted into the urine
17
Q
  • What transporters are found on the descending loop of henle?
  • What is a key feature about the descending LOH?
A
  • Aquaporin I (ON BASOLATERAL SIDE)
  • Permeable to water but impermeable to solutes
  • (as you go down the descending LOH, the filtrate becomes hyperosmolar as water is leaving and solutes become more concentrated (can get as high as 1400 mOsm)
18
Q
  • What is the key feature about the ascending (thick and thin) LOH?
A
  • Permeable to solutes (NaCl)
  • Impermeable to water (lots of tight junctions and no aquaporins)
19
Q
  • What are key transporters found on the thick ascending LOH? On which side of the cell are they found?
A
  • APICAL SIDE
    • NaK2CL Transporter
    • K+ Leak channels (K+ leave cell)
  • BASOLATERAL SIDE
    • Na+/K+ ATPase
    • Cl- leak channels (Cl- leave cell)
20
Q
  • How does the NaK2Cl transporter work?
A
  • Located on apical surface of thick ascending LOH
  • Gradient provided by Na+/K+ ATPase on basolateral side pumping Na+ out of the cell (creates a gradient for sodium to move), the K+ leak channel on the apical surface enabling K+ to leave (and permitting influx of K+ via concentration gradient) and Cl- leak channels on the basolateral side enabling Cl- to leave and giving Cl- a gradient to move down
  • NET EFFECT: One positive charge and two negatively charge particles have been reabsorbed from the lumen (leads to a transepithelial positive voltage)
    • Drives the movement of Na+, Ca2+, and Mg2+
21
Q
  • How do loop diuretics (furosemide) work?
A
  • Inhibit Na+/Cl- reabsorption by competing for the Cl- binding site on the NaK2Cl transporter
22
Q
  • What transporters are present in the distal tubule? On which side of the membrane are they located?
A
  • Na+-Cl- (NCC) cotransporter on apical surface
  • Cl- leak channel on basolateral surface
  • Na+/K+ ATPase on basolateral surface
  • Relatively impermeable to water
23
Q
  • How do thiazide diuretics work?
  • What are they used for?
A
  • Inhibit NCC and enhance Ca2+ reabsorption in the distal tubule by increasing Na/Ca2+ exchange
  • Reduce excretion and increase absorption of Ca2+
  • Used to treat kidney stones and osteoporosis
  • Decreases blood volume and pressure
  • Inhibits reabsorption of NaCl
24
Q
  • What is special about the collecting duct?
  • What types of transporters are found in the collecting duct? On which side of the membrane?
A
  • The collecting duct reabsorbs based on what the body needs and is regulated by hormones (primarily aldosterone and PTH)
  • Na+/K+ ATPase on basolateral side
  • AQP II on apical side (influenced by ADH/AVP/Vasopressin, ANP, BNP)
  • ENAC on apical side (influenced by aldosterone)
25
Q
  • What are the goals of aldosterone
  • What does it respond to directly?
  • What does it respond to indirectly?
A
  • Increase NaCl and water reabsorption
  • Increase K+ secretion
  • Directly responds to an increase in plasma K+ concentration
  • Indirectly responds to decreases in Na+, ECF volume and arterial pressure
26
Q
  • An increase in plasma K+ will lead to an increase in aldosterone secretion and an increase in _ and _
A
  • K+ secretion in the tubules
  • Urinary excretion of K+
27
Q
  • Which hormone activates aldosterone?
  • What happens as a result?
A
  • Angiotensin II
  • Increase in aldosterone
  • Increase in Tubular Na+ reabsorption (ENACs on apical surface)
28
Q
  • What is the MOA of loop diuretics such as furosemide?
A
  • Inhibits the NaK2Cl transporter on the apical surface of the thick ascending LOH
  • Decreased reabsorption of Na,K,Cl
  • Diuresis
  • Increased urine output
29
Q
  • How does K+ sparing spirinolactone work?**
A
  • Aldosterone dependent
  • Inhibits Na+/K+ exchange in distal tubule and collecting duct and promotes K+ retention and Na+ and water loss
  • Hypotensive effect
30
Q
  • Describe the steps that occur when you have a water deficit
A
  1. ADH secretion increases
  2. More H2O reabsorption in the collecting duct
  3. Small volume of concentrated urine excreted (can be concentrated up to 1200 mOsm)
31
Q
  • Decribe the key steps that occur with water excess
A
  • No ADH secreted
  • Distal and collecting tubules remain impermeable to water
  • Tubular fluid entering the distal tubule is hypotonic (100 mOsm/L) having lose salt without an accompanying loss in H2O in ascending LOH)
  • As the hypotonic fluid passes through the distal and collecting tubules, the medullary osmotic gradient cannot exert any influence b/c the late tubule is impermeable to H2O
  • In absence of ADH, 20% of filtered fluid that enters that distal tubule is not reabsorbed
  • Excretion of wastes and other solutes remains constant
  • Net result=large volume of dilute urine
32
Q
A
  • Proximal tubule 67%
  • Descending LOH 15%
  • Distal Tubule (Early part) 0%
  • Late Distal tubule and collecting duct (8-15%)
33
Q

What hormones influence Na+ reabsorption and where do they act in the nephron?

A
  • Proximal tubule
    • 65-70% Na+ reabsorption
    • Angiotensin II, NE, Epi, Dopamine
  • LOH
    • 25% Na+ reabsorption
    • Aldosterone, Angiotensin II
  • Distal Tubule
    • 5% Na+ reabsorption
    • Aldosterone, Angiotensin II
  • Late Distal Tubule and Collecting Duct
    • ~3% Na+ reabsorption
    • Aldosterone, ANP, BNP, urodilatin, uroguanylin, guanylin, angiotensin II