PSL301: Water 3 Flashcards
Tubular Function
value: normal GFR
> 90 mL/min or > 125 L/day
value: normal urine volume
0.5L - 2 L per day
why is there such a big difference between filtered volume and excreted volume?
> 99% of water & solutes are reabsorbed by the tubules
function of tubules
- reabsorb solutes & water
- secrete solutes & water
- maintain homeostasis
when everything is normal, intake…
What is this called?
intake = secretion
“steady state”
steady state
intake = secretion
when there is a deficit of something, intake…
intake > excretion
excretion decreased
when there is an excess of something, intake…
intake < excretion
excretion increased
How does the kidneys maintain homeostasis?
adjust how much is reabsorbed & secreted
What signals do the tubules receive, and what do they do?
- hormones
- nerves
- pH
- electrolyte concentrations
- pressure
signals modify reabsorption / excretion to keep body fluid composition normal
Hormone signals to the kidney
- vasopressin / ADH
- aldosterone
- ANG II
- PTH
purpose of ADH
water balance
purpose of aldosterone
Na & K balance
purpose of ANG II
Na & acid-base balance
purpose of PTH
Ca++ & phosphate balance
main nephron segments
- proximal tubule
- loop of Henle
- distal tubule
- collecting duct
the collecting duct is divided into…
- cortical collecting duct
2. medulla collecting duct
the Loop of Henle is divided into…
- Thick descending limb
- descending limb
- ascending limb
- thick ascending limb
function of tight junctions at the transporting epithelium
- keep cells attached to each other
- prevent movement between adjacent cells (must pass through epithelial cells)
The basolateral membrane of the epithelium faces the…
ECF / blood stream
The apical membrane of the epithelium faces the…
lumen of kidney / intestines
____ increases absorptive surface area on the __ side of the proximal tubule
brush border microvilli
lumen
Most of the reabsorption occurs in the…
proximal tubule
sites of reabsorption
- proximal tubule
- loop of Henle
- distal convoluted tubule & collecting duct
Glucose is reabsorbed in the…
all glucose is reabsorbed in the proximal tubule
How is K homeostasis maintained?
by secretion at the distal convoluted tubule & collecting duct
Most solutes & water homeostasis is controlled by the…
What is the exception?
distal convoluted tubule & collecting duct
Glucose, controlled by proximal tubule
What are the things reabsorbed / secreted by the kidneys? (5)
- water
- Na
- K
- glucose
- bicarb
How do transporting epithelial cells work?
Polarized, so have different transport proteins on each side. Solutes must pass through different ones to get to other side.
the Na/K ATPase is located on which membrane?
basolateral
the Na/K ATPase is next to…
peritubular capillary
what does the Na/K ATPase do?
pumps 3 Na out of cell
pumps 2 K into cell
- makes cell negative
- make [Na] in cell low
the Na/K ATPase has what effect on Na in the lumen?
can enter cell naturally (down electrochemical gradient) @ apical membrane
Na then leaves through Na/K ATPase @ basolateral membrane
What is the purpose of Na movement?
Drives the movement of other solutes by cotransporters and antiporters on the apical membrane
cotransporters
transport 2 things in the same direction
- movement of 1 thing down the gradient drives movement of other against the gradient
antitransporters
transport 2 things in opposite directions
- movement of 1 thing down the gradient drives movement of other against the gradient
movement of water at the proximal tubule
follows Na (moves into capillaries) - osmotic gradient
absorption & secretion t the proximal tubule is ___ because of the movement of sodium
passive
define: secondary active transport
an ion can move against the gradient by coupling with another that moves down the gradient
the Na/glu transporter is a(n)…
cotransporter
reabsorption of glucose
- Na/glu cotransporter moves glucose into cell (where it is high concentration)
- glucose moves out of cell on basolateral side using GLUT transporter
- Na/K ATPase pumps Na out of cell to keep intracellular Na low
which ions use sodium co-transport as a method to get through cells?
- glucose
- phosphate
- chloride
…
how is paracellular transport achieved (at the renal tubules)?
- through tight junctions
- selective
- have pores
- driven by gradients
- only some ions (Na, Cl, Ca, Mg…) can get through
diuretic drugs block…
lumenal Na transporters
- increase Na secretion
specific diuretics target specific transporters
common target of diuretics
- loop of Henle
- distal convoluted tubule
- collecting duct
how does each nephron segment differ?
- type of transport protein
- leakiness
- type of hormone receptors present
things that will affect leakiness in tubules
- nature of the tight junction
- presence of channels (e.g. aquaporins)
Trend of leakiness at the nephron tubules
Start off very leaky (proximal tubule)
Get tighter as you go on (collecting duct)
proximal tubule is the site of…
most reabsorption (Na, Cl, K, bicarb, water)
the most important lumenal Na transport protein at the proximal tubule is…
NHE3 (sodium-hydrogen exchanger)
NHE3 works by…
pump Na into the cell
pump H+ out of the cell
Purpose of NHE3
bicarb reabsorption
which cotransporters are only found on the proximal tubule?
- glucose
- phosphate
- amino acid
the proximal tubule is very leaky -> ____ reabsorption of Na. What does this mean?
isotonic
[Na] in lumen is the same as [Na] in plasma due to water moving with Na
The thick ascending limb reabsorbs ___% of ___
20 - 30%
filtered Na
what is the lumenal transport at the thick ascending limb?
Na/K/2Cl cotransporter (NKCC2)
NKCC2 is inhibited by…
furosemide (diuretic)
how permeable is the thick ascending limb to water?
not at all
fluid leaving the thick ascending limb is ____
hypotonic
less concentrated than plasma because water in tubule cannot get out
What concentrates the medullary interstitium? What is the necessary for?
Add salt without water
Necessary for urine concentration
the thick ascending limb has a ___ lumen and a ___ ISF
dilute
concentrated
the distal convoluted tubule reabsorbs ___% of _____
5 - 10%
filtered Na and water
what is the lumenal Na transporter in the distal convoluted tubule?
NCC (sodium chloride cotransporter)
NCC is inhibited by which diuretic?
thiazides
Which is more potent: thiazides or furosemides? Why?
furosemide.
thick ascending loop reabsorb more Na than the distal convoluted tubule
the distal convoluted tubule is important for…
urine dilution
when are thiazides used? furosemides?
furosemides used when you want a lot of Na+ lost in the urine.
thiazides used when you only want a bit more Na+ lost in the urine.
the collecting duct reabsorbs ____% of ____
1-3%
filtered Na
reabsorption at the collecting duct depends on…
body’s needs
what is the lumenal transport protein at the collecting duct?
ENaC (epithelial sodium channel)
the collecting duct has receptors for…
- aldosterone
- vasopressin
effect of aldosterone binding to the collecting duct
increase Na reabsorption
- increase amount of Na channels
- open more Na channels
effect of ADH binding to the collecting duct
increase water reabsoprtion
- increase aquaporin2
Effect of drugs on the collecting duct
collecting duct has low capacity, so it is easily affected by drugs
why is the collecting duct important?
- can generate large [ ] gradients
- establish final urine composition / concentration
the collecting duct is less permeable to ___ than Na. What does this cause?
Cl-
Causes lumen to be neg, so K+ will be secreted (down charge gradient)
the collecting duct is the site of regulation for the secretion of…
- Na
- K
- water
- ammonium
ammonium is secreted to regulate…
acid-base balance
There are __ transporters for glucose. They are…
2
in series: proximal and distal
Properties of the proximal glucose transporter
- low affinity
- high capacity
Properties of the distal glucose transporter
- high affinity
- low capacity
How does the SGLT protein work?
- Na+ binds
- creates a site for glucose
- glucose binding changes SGLT conformation
- Na+ released, glucose follows
what does “high affinity for glucose” mean?
can transport glucose even if the glucose gradient is very opposing
what is the proximal glucose transporter called?
SGLT2
what is the distal glucose transporter called?
SGLT1
How does SGLT1 have a higher affinity for glucose?
exchanges 2 Na for 1 glucose
2 Na creates a higher drive into the cell
SGLT2 is located…
S1 segment of the proximal tubule / early proximal tubule
SGLT1 is located…
S3 segment of the proximal tubule / late proximal tubule
job of SGLT1
remove all glucose from the lumen
glucose (in) : glucose (out) ratio for SGLT2
70:1
glucose (in) : glucose (out) ratio for SGLT1
5000:1
What happens when someone has glucose in the urine with normal blood glucose?
- problem with SGLT2
- no problem as long as they get enough calories
___ can be possible treatment for hyperglycemia and diabetes. What effect might this have?
SGLT2 inhibitor drugs.
- lower blood glucose
- lower weight
lumenal Na transport proteins
- Na cotransporters
- Na antiporters
- Na channels
___ has no large gradients because of ____
proximal tubule.
very leaky
___ has large gradients because of ____
collecting duct.
tight
Organic solute transporters are all…
proximal
water reabsorption is…
passive (osmotic gradient)
water reabsorption at the proximal tubule
follows Na isotonically
water reabsorption at the collecting duct
dependson the presence of ADH (aquaporin2)