Renal Tubular Transport Flashcards
What is the structure of the tubular epithelium? What separates the peritubular capillary from the lumen?
Epithelium with tight junctions
- interstitial fluid is also present
- basement and basolateral membrane present as well
What 2 general routes can things take to get reabsorbed into the peritubular capillary?
Paracellular path
- through tight junctions and interstitium
Transcellular path
- through the cell, via active or passive diffusion (water generally does osmosis)
What solutes from filtrate generally get reabsorbed? Excreted?
Reabsorbed >90%
- glucose
- bicarb
- Na+
- Cl-
- K+
Excreted
- urea (~50% excreted)
- creatinine
What are the 2 basic mechanisms for passive transport?
Simple diffusion:
down” electrochemical gradient via lipid bilayer or aqueous channels
Facilitated diffusion:
“down” electrochemical gradient; specific carriers are required
What are the 3 basic mechanisms for active transcellular solute movement?
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
How much of the filtrate is reabsorbed by the proximal tubule? What substances does it reabsorb?
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!
What does the proximal tubule secrete?
Several organic anions and cations (including drugs, drug metabolites, creatinine, urate) are secreted in proximal tubule
What powers transport in the proximal tubule?
Na-K-ATPase
What are some pertinent histological features of the proximal tubule?
Brush border
- apical membrane is rich with aquaporins to reabsorb water
Full of mitochondria
Basolateral membrane
- infoldings for ATPase
- helps power solute movement
What fraction of filtered water is reabsorbed in the PCT?
2/3
What is secreted in the proximal tubule? How does this compare to the osmolarity?
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)
What happens to inulin concentration in the proximal tubule compared to plasma inulin concentration as you proceed down the tubule?
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
What happens to tubule lumen glucose concentration compared to plasma glucose concentration as you proceed down the tubule?
Tubule glucose concentration should approach 0
If not, Wilford Brimley might kill you.
What happens to PAH concentration in the tubular lumen as compared to the plasma as you proceed down the tubule?
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
What provides the driving force for reabsorption of water and other solutes in the proximal tubule?
Proximal tubular Na+ Reabsorption
What facilitates transport in the proximal tubule? What direction is the transport, generally?
Polarity of epithelial cell membranes facilitates net Na+ unidirectional transport
What powers active transport in the proximal tubule? How are most solutes transported?
Powered by Na+,K+ ATPase in basolateral membrane
Na+ reabsorption is usually coupled to transport of or exchange for another solute
What 2 ways does Na+ get into peritubular capillary near the proximal tubule?
- Paracellular path - Na+ goes through leaky jxns and goes back into peritubular capillary
- 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
What substances does Na+ reabsorption facilitate transfer of? Are the substances moved in or out of the cell?
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
What are some mechanisms of secondary active transport in the proximal tubule?
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
What follows Na+ reabsorption in the PCT?
Water (reabsorbed)
Explain how Cl- is reabsorbed in the PCT.
- In early PCT, there’s no Cl- transporters
- Cl- becomes more concentrated in luminal fluid
- due to reabsorption of H2O and Na+ - Cl is initially reabsorbed through paracellular reabsorption
- driven by concentration gradient between lumen and peritubular interstitium - Specific Cl- channels (anion exchanger) later on in PCT allow for transcellular transport
What helps drive paracellular reabsorption of Ca, Mg, and K?
Slight positive charge in tubular fluid due to presence of Cl- channels in distal PCT
What happens to relative Cl- concentrations as you proceed down the proximal convoluted tubule?
Initially rises relative to luminal fluid osmolarity
Cl- concentration will start to decrease towards end of PCT
What must be completely reabsorbed by the PCT?
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
Do the kidneys regulate plasma concentrations of glucose and AAs?
No - done by liver and endocrine system
What is the basic mechanism of tubular reabsorption of glucose and amino acids?
- Uptake across luminal membrane
- coupled to Na+ down its concentration gradient
- dependent on Na+/K+ ATPase
- against concentration gradient - Exit through basolateral membrane
- via facilitated diffusion
Secondary active transport
- only transcellular pathways
What is the mechanism of glucose reabsorption in the proximal tubule?
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
Is glucose reabsorption saturable?
Yes, if filtered amount of glucose exceeds capacity of nephrons to reabsorb it
- limited number of Na+/glucose cotransporters in luminal membrane
What happens when glucose isn’t entirely reabsorbed out of the filtrate?
Glucose appears in urine - glucosuria
Can cause osmotic diuresis
What if you have normal serum glucose but glucosuria?
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
At what plasma glucose concentrations do we start to see glucosuria?
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
Why does urine output increase in Diabetes mellitus?
Osmotic diuresis
