proximal tubule

Question 1

Proximal tubule is responsible for..

Answer 1

reabsorbing the (~2/3) of the filtered salt and water

Question 2

Tubular reabsorption

vs

Tubular secretion

Answer 2

Tubular reabsorption: tubular fluid –> the interstitium then into the peritubular capillaries

• Active or passive transport
• Quantitatively greater than secretion

Tubuular secretion: interstitial fluid –> tubular fluid

Question 3

What are the 3 major characteristics of solutes that are actively transported by renal tubules against their conc gradient using ATP?

Answer 3

• Competitive inhibition
  
  • ​Ex) Glucose & fructose compete for the Na-glucose cotransporter
• Metabolic inhibition
  
  • ​Low ATP will block the Na,K-ATPase
• Transport maximum

Question 4

At normal plasma [glucose], all the filtered glucose is reabsorbed by the …

Answer 4

Na-glucose cotransporter on the luminal membrane of the proximal tubule cells

Question 5

When does glucose start getting excreted into urine?

Answer 5

When [glucose]_plasma gets above ~200-250 mg/dL, all the Na-glucose cotransporters are saturated and glucose reabsorption has hit transport maximum (T_MAX)

Question 6

What mechanism lowers [Na⁺] within the proximal tubule cell and therefore allows passive Na+ movement into the proximal tubule cell?

Answer 6

Basolateral membrane Na+/K+ ATPase pumps

Actively transports Na+ out into the interstitium to keep [Na+] low inside the proximal tubuel cell for cotransporters to bring more Na+ inside.

Question 7

Name a solute that is passively reabsorbed.

Answer 7

Urea

Question 8

What mechanism is responsible for generating the concentration gradient for the passive reabsorption of urea into the interstitial fluid?

Answer 8

Water getting reabsorbed in the renal tubule concentrates urea in the tubule –> passive reabsorption of ureaout to the interstitial fluid

Question 9

What’s the relationship between urine flow and passive reabsorption?

Answer 9

Higher urine flow -> lower passive reabsorption

This is because higher urine flow means H₂O isn’t being reabsorbed. H₂O reabsorption is needed to concentrate urea in the tubule for the passive reabsorption of urea.

Question 11

Why is there more urea in the distal tubule than there is the proximal tubule?

Answer 11

Urea is reabsorbed at the proximal tubule, but was secreted into the loop of Henle.

Gets reabsorbed by the inner medullary collecting duct

Question 12

Urea undergoes net tubular ____

Answer 12

net reabsorption

Was reabsorbed at prox tubule, secreted in the loop, reabsorbed again in the collecing duct.

Only 40% of filtered urea gets excreted.

Question 13

In addition to the Na-aa/glucose/citrate/succinate/phosphate/etc cotransporters on the apical membrane and the Na-K ATPase on the basolateral membrane, there’s the ___ controlling bicarbonate reabsorption

Answer 13

Na⁺/H⁺ exchanger

Question 14

What drives passive Cl- reabsorption by the early proximal tubule?

Answer 14

The Na+/solute cotransport and the Na+/H+ exchange results in the generation of a small lumen-negative potential gradient –> drives a small amt of passive Cl- reabsorption

Question 15

Why is [Cl^-] high in the tubular fluid of the late proximal tubule?

What does this drive?

Answer 15

Na/solute and Na/HCO₃^- in the early proximal tubule broke up all the NaCl that was in the tubular lumen and left behind Cl^- for the late proximal tubule.

High [Cl-] in the late prox tubule drives

• the Cl-/anion exchanger
• passive reabsorption of Cl- via the paracellular process

Question 16

Describe the major mechanisms of Na+ entry into the cell across the late proximal tubule

Answer 16

• Na, K ATPase
• Cl-/anion exchanger brings Cl- into the cell and sends out OH^-, HCO₃^-, and formate
  
  • These anions combine with the H+ sent out from the Na+/H+ exchanger –> drives Na+ entry

Net: NaCl entry into the proximal tubule cell

Question 17

The passive reabsorption of Cl- results in a small lumen-___ transepithelial potential gradient.

This drives __.

Answer 17

Cl- leaving creates a small lumen-positive transepithelial potential gradient.

This drives the passive reabsorption of Na+ and K+ via the paracellular pathway

Question 18

Describe the reabsorption of filtered HCO₃^-

Answer 18

1. H+ and HCO₃^- in the tubular lumen from the Cl-/anion exchanger combine into H₂CO₃
2. Carbonic anhydrase on the luminal membrane turn it into H₂O & CO₂
3. CO₂ diffuses into the prox tubule cell
4. Carbonic anhydrase in the cell turn it back into HCO₃^-, which will leave basolateral membrane via
   
   1. Bicarbonate channels
   2. Cl-/HCO₃^- exchangers
   3. Na⁺/HCO₃^- cotransporter on

Question 19

Acetazolamide

Answer 19

Carbonic anhydrase inhibitor

–> inhibits reabsorption of Na⁺, HCO₃^-, NaCl, and water by proximal tubule cells

–> increase in urine flow (diuresis) and Na excretion (natriuresis)

Question 20

Two major mechanisms mediate water reabsorption in the proximal tubule

Answer 20

• Luminal hypotonicity: the reabsorption of all those solutes makes the tubular fluid hypotonic to the interstitial fluid & plasma –> water reabsorption
• Axial anion asymmetry: The HCO₃^- that built up in the late proximal tubule has a higher reflection coefficient than the Cl- that built up, meaning it exerts a greater osmotic effect –> water follows HCO₃^- reabsorption

Question 21

What drives the solutes and water in the interstitial environment into the peritubular capillary?

Answer 21

High oncotic pressure in peritubular capillary due to plasma proteins

Also, hydrostatic pressure of interstitial fluid

Question 22

Angiotensin II & Catecholamines (e.g. norepinephrine) do what to the proximal tubule?

Answer 22

Stimulates proximal tubular NaCl, NaHCO₃^-, and water reabsorption

Question 23

Vasodilator hormones (e.g. dopamine) have what impact on proximal tubule?

Answer 23

Inhibits reabsorption

Question 24

Extracellular fluid volume expansion (e.g. isotonic saline) would have what impact on reabsorption?

Answer 24

Decreases reabsorption

Extracellular fluid volume expansion reduces the colloid osmotic pressure of the peritubular capillaries .

–> Water in the interstitium doesn’t enter.

–> Interstitial hydrostatic pressure increases

–>Tight jxns between proximal tubule cells become more permeable, so fluid and solutes to diffuse back into the proximal tubular fluid

Question 25

Giving a patient isotonic saline should have what impact on urine flow and Na excretion?

Answer 25

Increased urine flow

Increased Na excretion

Question 26

Glomerulotubular balance - what is it?

Answer 26

The more filtered at the glomerulus, the more reabsorbed at the proximal tubule to prevent severe solute loss.

Ensures that a constant fraction of the filtered load is reabsorbed

Question 27

Explain how glomerulotubular balance connects GFR to reabsorption

Answer 27

• If GFR is increased with no change in RPF, then filtration fraction increases.
• Increased filtration fraction more fluid was filtered out of the glomerular capillary blood.
• When the glomerular capillary becomes the peritubular capillary, it now has a higher oncotic pressure to drive reabsorption

Question 28

Decreases in GFR do what to reabsorption?

Answer 28

Decreased GFR -> decreased filtration fraction -> decreased peritubular oncotic pressure -> decreased reabsorption

Question 29

Glucose, amino acids, inorganic anionss, and organic acid anions are transported out of the lumen of the proximal tubule by…

Answer 29

active transport

Question 30

Aquaporins are on which side of the prox tubule?

Answer 30

Both apical and basolateral!