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Kathleen's Renal I > Renal Tubular Transport > Flashcards

Renal Tubular Transport Flashcards

1
Q

What is the structure of the tubular epithelium? What separates the peritubular capillary from the lumen?

A

Epithelium with tight junctions

  • interstitial fluid is also present
  • basement and basolateral membrane present as well
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2
Q

What 2 general routes can things take to get reabsorbed into the peritubular capillary?

A

Paracellular path
- through tight junctions and interstitium

Transcellular path
- through the cell, via active or passive diffusion (water generally does osmosis)

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3
Q

What solutes from filtrate generally get reabsorbed? Excreted?

A

Reabsorbed >90%

  • glucose
  • bicarb
  • Na+
  • Cl-
  • K+

Excreted

  • urea (~50% excreted)
  • creatinine
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4
Q

What are the 2 basic mechanisms for passive transport?

A

Simple diffusion:
down” electrochemical gradient via lipid bilayer or aqueous channels

Facilitated diffusion:
“down” electrochemical gradient; specific carriers are required

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5
Q

What are the 3 basic mechanisms for active transcellular solute movement?

A

Primary active transport:

  • ATP hydrolysis provides energy
  • against electrochemical gradient

Secondary active transport:
- ‘downhill’ movement of one substance proved potential energy for ‘uphill’ movement of another substance

Pinocytosis:
- protein reabsorption

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6
Q

How much of the filtrate is reabsorbed by the proximal tubule? What substances does it reabsorb?

A

Proximal tubule reabsorbs 60-80% of the filtrate

Most of filtered H2O, Na+, K+, Cl-, bicarbonate, Ca2+, phosphate
Normally, all the filtered glucose, amino acids

This equates to roughly 130 of the 180 L that is filtered daily!

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7
Q

What does the proximal tubule secrete?

A

Several organic anions and cations (including drugs, drug metabolites, creatinine, urate) are secreted in proximal tubule

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8
Q

What powers transport in the proximal tubule?

A

Na-K-ATPase

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9
Q

What are some pertinent histological features of the proximal tubule?

A

Brush border
- apical membrane is rich with aquaporins to reabsorb water

Full of mitochondria

Basolateral membrane

  • infoldings for ATPase
  • helps power solute movement
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10
Q

What fraction of filtered water is reabsorbed in the PCT?

A

2/3

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11
Q

What is secreted in the proximal tubule? How does this compare to the osmolarity?

A

Creatinine and urea are secreted into the proximal tubule
- both substances reach a higher osmolarity than the surrounding tubular fluid

All reabsorbed substances quickly decrease to a concentration much lower than the tubular fluid as you progress further through the proximal tubule.

(See slide 15)

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12
Q

What happens to inulin concentration in the proximal tubule compared to plasma inulin concentration as you proceed down the tubule?

A

Inulin will be 3x as concentrated in tubule lumen compared to plasma

Remember: 2/3 of water is reabsorbed in proximal tubule, and there is no reabsorption of filtered inulin

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13
Q

What happens to tubule lumen glucose concentration compared to plasma glucose concentration as you proceed down the tubule?

A

Tubule glucose concentration should approach 0

If not, Wilford Brimley might kill you.

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14
Q

What happens to PAH concentration in the tubular lumen as compared to the plasma as you proceed down the tubule?

A

PAH is secreted completely into the proximal tubule as 2/3 of water is reabsorbed

PAH should be 10x or more concentrated in the proximal tubule

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15
Q

What provides the driving force for reabsorption of water and other solutes in the proximal tubule?

A

Proximal tubular Na+ Reabsorption

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16
Q

What facilitates transport in the proximal tubule? What direction is the transport, generally?

A

Polarity of epithelial cell membranes facilitates net Na+ unidirectional transport

17
Q

What powers active transport in the proximal tubule? How are most solutes transported?

A

Powered by Na+,K+ ATPase in basolateral membrane

Na+ reabsorption is usually coupled to transport of or exchange for another solute

18
Q

What 2 ways does Na+ get into peritubular capillary near the proximal tubule?

A
  1. Paracellular path - Na+ goes through leaky jxns and goes back into peritubular capillary
  2. Transcellular path - Na+ is transported into cell, then is used via Na+/K+ ATPase to move K+ back into cell
    - Na+ is reabsorbed back into peritubular capillary after crossing luminal membrane
19
Q

What substances does Na+ reabsorption facilitate transfer of? Are the substances moved in or out of the cell?

A 
Na+ reabsorption:
moves H+ into tubular lumen
moves glucose into luminal membrane
moves K+ and 2 Cl- into luminal membrane
moves K+ into luminal membrane via Na+/K+ ATPase
20
Q

What are some mechanisms of secondary active transport in the proximal tubule?

A

Tubular lumen: luminal membrane
SGLT - glucose and Na+ into cell
Na+ & AAs into cell
NHE - Na+ in, H+ out

Luminal membrane: interstitial fluid
GLUT - glucose out of cell
Na+/K+ ATPase - K+ in, Na+ out
AAs - out

21
Q

What follows Na+ reabsorption in the PCT?

A

Water (reabsorbed)

22
Q

Explain how Cl- is reabsorbed in the PCT.

A
  1. In early PCT, there’s no Cl- transporters
  2. Cl- becomes more concentrated in luminal fluid
    - due to reabsorption of H2O and Na+
  3. Cl is initially reabsorbed through paracellular reabsorption
    - driven by concentration gradient between lumen and peritubular interstitium
  4. Specific Cl- channels (anion exchanger) later on in PCT allow for transcellular transport
23
Q

What helps drive paracellular reabsorption of Ca, Mg, and K?

A

Slight positive charge in tubular fluid due to presence of Cl- channels in distal PCT

24
Q

What happens to relative Cl- concentrations as you proceed down the proximal convoluted tubule?

A

Initially rises relative to luminal fluid osmolarity

Cl- concentration will start to decrease towards end of PCT

25
Q

What must be completely reabsorbed by the PCT?

A

Large amounts of organic nutrients (glucose, amino acids) are filtered each day, and they must be retained.

No reabsorption in more distal segments, so they are completely reabsorbed by the PCT

26
Q

Do the kidneys regulate plasma concentrations of glucose and AAs?

A

No - done by liver and endocrine system

27
Q

What is the basic mechanism of tubular reabsorption of glucose and amino acids?

A
  1. Uptake across luminal membrane
    - coupled to Na+ down its concentration gradient
    - dependent on Na+/K+ ATPase
    - against concentration gradient
  2. Exit through basolateral membrane
    - via facilitated diffusion

Secondary active transport
- only transcellular pathways

28
Q

What is the mechanism of glucose reabsorption in the proximal tubule?

A

Na+ and glucose are transported together into cell from tubular fluid
- via Na+/glucose cotransport

Glucose leaves cell via diffusion

Na+ leaves cell via Na+/K+ ATPase

29
Q

Is glucose reabsorption saturable?

A

Yes, if filtered amount of glucose exceeds capacity of nephrons to reabsorb it
- limited number of Na+/glucose cotransporters in luminal membrane

30
Q

What happens when glucose isn’t entirely reabsorbed out of the filtrate?

A

Glucose appears in urine - glucosuria

Can cause osmotic diuresis

31
Q

What if you have normal serum glucose but glucosuria?

A

Problems with the transporters themselves will result in normal serum glucose with glucosuria

Change in GFR with dilation of afferent arteriole and efferent arteriolar constriction can cause this too

32
Q

At what plasma glucose concentrations do we start to see glucosuria?

A

Glucosuria is detectable when plasma glucose concentration reaches 200mg/100mL

Transport maximum for luminal fluid glucose is reached when plasma glucose is at ~400mg/100mL

YMMV, depending on GFR

33
Q

Why does urine output increase in Diabetes mellitus?

A

Osmotic diuresis

Kathleen's Renal I (9 decks)

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