Lecture 19 - Na+ handling by the Kidney I Flashcards
What is our daily source of Na+?
Dietary intake - 100 to 300 mmol/day
What is the daily loss of Na+?
Sweat - 20 to 50 mmol/day
Faeces - 5 to 10 mmol/day
Urine - few to 500 mmol/day*
*Vomit, diarrhoea, menstruation
What is urine controlled by?
Urine is under hormonal control - under sedentary conditions we won’t have as much excretion of salt as we would when exercising
What is the average daily filtered load of Na+
The body has a daily filtered load of sodium of around 27,000 mmol
What segments of the nephron are permeable to Na+
The segments of the nephron permeable to sodium are the proximal tubule (convoluted and straight), the thin and thick ascending loop of Henle, the distal tubule (early and late), as well as the collecting duct
What segment of the nephron is not permeable to Na+?
Thin descending limb of loop of Henle
Which of the following statements is TRUE?
A. The extracellular fluid Na+ concentration is 170mM.
B. Normal blood pressure is 150/90 mm of Hg.
C. If you have a high NaCl diet you will excrete more Na+ than normal.
D. All segments of the Nephron can reabsorb Na
C. If you have a high NaCl diet you will excrete more Na+ than normal.
What % of Na+ reabsorption does the PT do?
67% or 2/3
What is the powerhouse segment of the nephron?
The proximal tubule
How is Na+ reabsorbed in the PT?
Via Na+ coupled transporters in the apical membrane
Na+ - glucose cotransporters (SGLT)
Na+ / H+ exchangers
Na+ - amino acid cotransporters
Where is SGLT2 found?
proximal convoluted tubule
What is the function of SGLT2?
Bulk of the glucose reabsorption
- Low affinity for glucose, but high capacity
- 1:1 Na+ : glucose stoichiometry (electrogenic)
What does Phloridzin inhibit?
Both SGLT1 and SGLT2
Where is SGLT1 found?
Proximal straight tubule
What is the function of SGLT1?
Reabsorbs the remainder of glucose
- High affinity for glucose; low capacity
- 2:1 Na+ : glucose stoichiometry (electrogenic)
What is the dominant Na+/H+ exchanger isoform in the PT?
NHE3 is the dominant apical membrane isoform
How does NHE3 facilitate Na+ reabsorption?
Moves Na+ down concentration gradient for exchange of H+ up concentration gradient
Also used in pH balance
Which of the following statements is FALSE?
A. The Proximal tubule is the ‘powerhouse’ of the Nephron.
B. 100% of filtered glucose is reabsorbed by the SGLT2 and SGLT1 of the Proximal tubule cells.
C. If you have a high NaCl diet you will excrete more Na+ than a person who has a NaCl normal.
D. SGLT2 has a higher affinity for glucose than SGLT1.
D. SGLT2 has a higher affinity for glucose than SGLT1.
What % of Na+ absorption does the Thin and Thick Ascending Loops of Henle (L of H) do?
25%
What Na+ transporter is found in the apical membrane of the Thin and Thick Ascending Loops of Henle (L of H)?
Na+-K+-2Cl- cotransporter (NKCC2)
How does NKCC2 facilitate Na+ reabsorption?
Requires Na+, K+, and Cl- to function
Na+ and Cl- move down concentration gradient; K+ moves against its gradient
What disease can effect NKCC2?
Bartter’s syndrome
What can inhibit NKCC2?
NKCC2 is selectively inhibited by ‘loop diuretics’ bumetanide and frusemide
How does the early and late distal tubule differ in the reabsorption of Na+?
Early distal tubule has transport function similar to the TAL of the Loop of Henle
Late distal tubule has transport function similar to the collecting duct
What % of Na+ reabsorption does the DT do?
5%
What Na+ transporter found in the early distal tubule?
Na+-Cl- cotransporter (NCCT)
What Na+ transporter found in the late distal tubule and collecting duct?
Na+ channels (ENaC)
Describe Na+-Cl- cotransporter (NCC)
Found apical membrane of early DT
Na+ and Cl- both required to function
60% molecular similarity to NKCC2
What can inhibit NCC?
Thiazide diuretics
Which of the following statements is TRUE?
A. Cells of the Thin and Thick Ascending Loops of Henle reabsorb 30% of the filtered Na+.
B. The Na+-Cl- cotransporter is the main transport protein that secretes NaCl by the Thin/Thick Ascending Limbs.
C. The Na+-K+-2Cl- cotransporter is inhibited by thiazide diuretics.
D. The cells of the Distal Tubule reabsorb 5% of the filtered Na+.
D. The cells of the Distal Tubule reabsorb 5% of the filtered Na+.
Where do we have the fine tuning of Na+?
The collecting ducts
What % of Na+ reabsorption does the collecting ducts do?
2.5%
What route does Na+ take in tight absorptive epithelia?
Transcellular - not paracellular
What Na+ transporter is found in the CD?
Apical Epithelial Na+ channel (ENaC)
What drug can inhibit/block ENaC?
Amiloride
In areas of Na+ reabsorption, what Na+ transporter is found in the basolateral membrane?
Na+/K+ ATPase
What is ENaC regulated by?
Aldosterone
What is the composition of ENaC?
Composed of 3 subunits (1a : 1b : 1g)
* each subunit - 2 transmembrane domains
* each subunit has a large extracellular loop
* PY motif (PPPXY) – proline (P) and tyrosine (Y) is important in protein-protein interactions
What are some molecular defects/diseases of ENaC?
Liddle`s syndrome
Pseudohypoaldosteronism Type I
What is Liddle’s syndrome?
A gain of function due to mutations of COOH- termini of b and g subunits of ENaC
– Too many ENaC channels
What is Pseudohypoaldosteronism Type I?
A loss of function due to a mutation of the NH2- terminus of the a subunit of ENaC
– Too few ENaC channels
