L19 Flashcards
Even in a normal diet you still eat more Na then you need therefore you execrate it
Homeostasis of Na is important for many things what is an important reason
maintaining BP
when it is not maintained properly blood pressure (is usually high because of high Na diet) which leads to cardiovascular disease
why is high BP known as the silent killer
Blood pressure is the silent killer as it causes heart attack, renal disease
Na is maintained at a very narrow range.
what is the intra and extracellular conc of Na and why is it important that these are maintained
extracellular fluid at about 150mmoles of Na
intracellular at 10mmoles
Na is involved in many cellular functions therefore it needs to be maintained so that cellular processes can run as normal
maintaining a diet rich in fruits and vegetables can decrease BP by how much
8-15mmHg
what is normal BP, high BP and low BP
n = 120/80
low = 90/50
high = 180/110
do athletes tend to have high or low BP
low
what are sources of Na
your diet
how you you loos Na from the body
sweat ect (how much mM)
Sweat - 20 to 50 mmol/day
Faeces - 5 to 10 mmol/day
Urine - few to 500 mmol/day
Vomit, diarrhea, menstruation
decribe the aim of Na homeostasis
the nephrons are responsible for..
Daily Na+ Gain = Daily Na+ Loss
net loss and gain = 0
how do the nephrons handle the filtered load of Na
Because of the various transporters in the apical and basolateral membranes of the nephron
what segments of the nephron are permeable to Na
• Proximal Tubule
– Convoluted
– Straight
• Thin and Thick
Ascending Loop of
Henle
• Distal Tubule
– Early
– Late
• Collecting Duct
which parts of the nephron are NOT permeable to Na
thin descending limb
Which of the following statements is TRUE?
A. The extracellular fluid Na+ concentration is 170 mM.
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+
A. 150mM
B. 120/90mmHg
D. the thin descending limb is impermeable to Na
therefore C is correct
how much Na does the proximal tubule receive per day
• receive ~27,000 mmol of Na+
how much Na does the proximal tubule reabsorb per day
• reabsorbs about 2/3 filtered Na+
~18,000 mmol
what kind of epithelium does the PT contain
• a ‘Leaky’ absorptive epithelium
how does the PT reabsorb Na
3 transporters
• Na+ coupled transporters (apical membrane) these are forms of secondary active transport
Na+ - glucose cotransporters (SGLT2)
Na+ / H+ exchangers (NHE)
Na+ - amino acid cotransporters
where is Na+-Glucose Co-Transporter - SGLT2 located
• proximal convoluted tubule
what is SGLT2 responsible for
• bulk of the glucose reabsorption
what are the characteristics of SGLT2
- low affinity for glucose, but high capacity
- 1:1 Na+ : glucose stoichiometry (one glucose and one Na)
(electrogenic)
what is SGLT2 and SGLT1 inhibited by
• inhibited by phloridzin
how many transmembrane domains do SGLT 1 and 2 have
Big proteins with 14 transmembrane membrane domains
where is Na+-Glucose Co-Transporter - SGLT1 located
• proximal straight tubule
describe the characteristics of SGLT1
- high affinity for glucose; low capacity
- reabsorbs the remainder of glucose
• 2:1 Na+ : glucose stoichiometry (2Na for 1 glucose)
(electrogenic)
where does the H+ come from that NHE is pumping out of the cell
Carbonic anhydrase adds CO2 and H2O together to form H+ and HCO3-
H+ is used for the NHE pump (apical)
Bicarbonate is really important for acid base balance as it is used in the blood to reduce acidosis (basolateral)
what is the dominant Na+/H+ exchanger
• NHE3 is the dominant apical membrane isoform
what NHE do we need to know about (theres 4)
- NHE3 is the dominant apical membrane isoform
* also NHE1, NHE2, NHE4 in kidney
what is the role of NHE
- 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 is false (should be the other way around)
how much Na does the thick and thin ascending limbs of henle receive per day
• ~ 8,900 mmol of Na+ is received by the Loops of Henle each day
C2)
how much Na does the thick and thin ascending limbs of henle reabsorb per day
• thin and thick ascending limbs reabsorb about 25% (~ 6,750 mmol) of the total
filtered Na+
what transporter is used to reabsorbed Na in the thick and thin ascending limbs
• Na+-K+-2Cl- cotransporter (NKCC2)
what is the role of the thick ascending limb of henle
The overall function is to create polarity so that NA, K, Ca and Mg is reabsorbed
where is NKCC2 located
• apical membrane location in the thin and thick ascending limbs
what is NKCC2 doing to Na, K and Cl
• requires Na+, K+, and 2Cl- to function
• Na+ and Cl- move down concentration
gradient; K+ moves against its gradient
what is NKCC2 inhibited by
• selectively inhibited by ‘loop diuretics’
bumetanide and frusemide
Different versions of these inhibitors have been modified to have an even greater effect
why would you want to inhibit NKCC2
For blood pressure regulation
how much Na does the distal tubules receive per day
• ~ 2,150 mmol of Na+ is received by the distal tubules each day
describe the characteristics of the distal tubule for Na reabsorption
- early distal tubule has transport function similar to the Thick AL of the Loop of Henle (NCCT)
- late distal tubule has transport function similar to the collecting duct (ENaC)
how much Na does the distal tubule reabsorb per day
• distal tubules reabsorb ~1,350 mmol of daily filtered Na+ (~ 5%)
what channels are responsible for the Na reabsorption in the early and late distal tubule
- Na+-Cl- cotransporter (NCCT) – early distal tubule
* Na+ channels (ENaC) – late distal tubule (and collecting duct)
where is the NA/Cl cotransporter (NCC) located
• apical membrane location in early DT
NKCC2 and NCC are very molecularly similar. what % similar are they
• 60% molecular similarity to NKCC2
what is NCC inhibited by
• inhibited by thiazide diuretics
what cotransporter is Goodman’s syndrome associated with
NCC
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+.
A. 25%
B. reabsorbs
C. NCC is inhibited by thiazide diuretics. NKCC is inhibited by loop diuretics
D is correct
Collecting Ducts – ‘fine-tuning’ of Na+
how much Na do they receive per day
• receive ~ 800 mmol of daily Na+ filtered
what epithelia does the CD contain
• ‘Tight’ absorptive epithelium
how much Na does the CD reabsorb per day
• reabsorb about ~ 2.5% of the filtered Na+
~ 700 mmol
how does the CD reabsorb Na
• Apical Epithelial Na+ channel (ENaC)
what is ENaC blacked by
blocked by amiloride (< 1 µmol/L)
the collecting duct has 2 different cell types
what are these, which contains ENaC and what is the role of the 2 cells
principal cell contains ENaC and is responsible for Na and K balance
intercalated cell is for pH balance
describe the composition of ENaC
composed of 3 subunits (1a : 1b : 1g)
• each subunit - 2 transmembrane domains
• each subunit has a large extracellular loop
ENaC has proline rich domains
what is the motif of ENaC
• PY motif (PPPXY)
- proline (P)
- tyrosine
(Y) is important in protein-protein interactions, - (X) is another amino acid
what is ENaC regulated by
• regulated by aldosterone
what is liddle’s syndrome
• Liddle`s syndrome -
gain of function due to mutations of COOH- termini of beta and gamma subunits of ENaC
– Too many ENaC channels = too much reabsorption = hypertension
what is Pseudohypoaldosteronism Type I
Pseudohypoaldosteronism Type I is a loss of function due to a mutation of the NH2- terminus of the a subunit
– Too few ENaC channels therefore not enough reabsorption
