In the early PCT, what are the ions doing?
bicarb, NaCl, glucose, A.A, other organics are reabsorbed into the blood via transporters
K is reabsorbed via paracellular transport (in between cells)
Water is reabsorbed passivly
How much of each thing is reabsorbed in the PCT?
Na, K, water
Glucose and Amino Acids
~100% (that’s why its bad when you see protein and sugar in someone’s urine)
Na Bicarb reabsorption in the PCT is initated by what?
Na/H exchanger located in luminal membrane of the PCT epithelial cell
What does carbonic anhydrase do?
forms H2CO3 from CO2 and water
which then breaks down into H and Bicarb to be used later in important things
In all portions of the nephron, Na is pumped into the interstitium to maintian low intracellular Na. How is this done?
Na/K ATPase in the basolateral membrane pumps the reabsorbed Na into the interstitium
In the straight/late Proximal Tubule, acid secretory systems secrete what into where?
secrete acids (NSAIDs, uric acid, diuretics, Abx) into luminal fluid from the blood
diuretics are deliverd to the luminal side of the tubule where they act
Clinical Application: Inhibition of carbonic anhydrase does what?
results in decrease of H ion formation inside the PCT cell, decreasing Na/H antiporter, increasing Na and bicarb in the lumen and increasing diuresis (peeing)
urine pH is increased and body pH is decreased
What is happening in the thin limb of the loop of Henle?
water is reabsorbed from the thin limb into the blood
it is water permeable and impermeable to ions/solutes
What is happening at the thick ascending limb of the loop of henle?
reabsorbs Na (25%) and is impermeable to water
What is going on with NaCl around the thick ascending limb of the LOH
NaCl in the interstitial space dilutes the tubular fluid
it is transported into the luminal membrane by the NKCC2 cotransporter
this is what establishes teh ion concentration gradient in the interstitium of the renal cortex and medulla
The NKCC2 cotransporter increases intracellular K which leaads to what?
back diffusion of K into tubular lumen, allowing a lumen positive electrical potential to drive reabsorption of cations (Mg and Ca) via paracellular pathway.
Clinical Applications: inhibition of the NKCC2 cotransporter by loop diuretics in the thick ascending LOH causes what?
Results in decreased intracellular Na, K, and Cl in the Ascending LOH, decreased back diffusion of K and positive potential, decreased reabsorption of Ca and Mg, and increased diuresis; urine pH is decreased and body pH is increased
What is happening at the DCT?
10% NaCl reabsorbed, further dilutes tubular fluid
pretty impermeable to water
NaCl is tranported via thiazide sensitive Na and Cl cotransporter
Ca is passively reabsorbed by Ca channels (regulated by PTH)
Clinical Applications at the DCT by inhibition of Na/Cl tranporter by what compound does what?
Inhibition of Na/Cl cotransporter by thiazide diuretics inhibits NaCl reabsorption in the DCT, resulting in increased luminal Na and Cl and increased diuresis
urine pH is decreased, body pH is increased
What is going on at the Collecting Duct?
2-5% of NaCl reabsorption via ENaC
most important side of K secretion by kidney and which all diuretic induced changes in K balance occur
diuretics act upstream of CD and increase Na delivery, which helps with K secretion
Na/K APTase pumps Na out of cell into interstitium/blood while pumping K into the cell where it can exit down the concentration gradient of the lumen/urine
How does aldosterone affect the collecting duct?
Aldosterone increases the expression of both ENaC and basolateral Na/K ATPases, leading to an increase in NA reabsorption and K secretion (causes retention of water, increase in BV, and increase in BP)
helps H to be secreted by H ATPases into lumen to increase acidity of urine
How does ADH affect the collecting duct?
controls the permeability of the CD to water by controlling expression of AQ2 water channels that insert into the apical membrane
ADH levels are regulated by serum osmolality and volume status
In the absence of ADH, cortical collecting tubule and collecting duct is impermeable to what?
water and dilute urine is produced as a result
(water can’t get out so urine is really water, less salty)
ETOH decreases ADH release and has what effect?
As a result of the decrease in ADH, there is an increase in urine production
why you have to pee so much at the bar
Clincial Application functioning at the collecting duct
Essentially same result, just two ways to go about it.
Two types for K sparing diuretics
- inhibition of the aldosterone results in decreased expression of ENaC, increasing Na excretion and increasing diuresis; K excretion is decreased; urine pH is increased and body pH is decreased
- Inhibition of ENaC directly results in decreased expression of ENaC, increasing Na excretion and increasing diuresis; K excretion is decreased, urine pH is increased and body pH is decreased
Add Tables after watching lecture if needed
Normally, Na is secreted or reabsorbed where depending on needs?
Na is secreted or reabsorbed in the late Distal Tubule and cortical Collecting Duct
What are the most important factors that stimulate Na reabsorption?
What are the most important factors that stimulate Na secretion?
Na deficiency, low Na diet, hyponatremia
Na loss through SEVERE diarrhea
- increased Na conc. in ECF
- increased tubular flow rate
K is secreted or reabsorbed where?
Most important factors that stimulate K reabsorption?
Most important factors that stimulate K secretion?
in the late Distal Tubule and cortical collecting duct
- K deficiency, low K diet, hypokalemia
- K loss through SEVERE diarrhea
- increased ECF K conc.
- increased tubular flow rate
- Na delivery to cortical CD
How do the principal cells in the CD become permeable to water?
ADH inserts AQ2 channels into the membrane
Describe urea permeability in the inner medullary collecting ducts?
During anti-diuresis, water but not urea, is reabsorbed in the cortical collecting duct. Urea flows further thru the fuct and is concentrated in the inner medullary collecting duct.
High concentration of urea here promotes passive reabsorption down its gradeint from the IMCD into the interstitium.
It flows in the interstitium to the LOH where the concentration is lower and then flows down its gradient again into the LOH, thus recycling itself.
Describe the NKCC2 in the Thick Ascending Loop of Henle
ADH increases permeability of NaCl at the apical membrane of the thick ascending LOH by increasing presence of the NKCC2 channels
this allows more NaCl reabsorption, increasing osmolality of the interstitium.
When combined with urea being reabsorbed from the IMCD, the medullary interstitium becomes very concentrated.
The greater the medullary hyperosmolalitym the greater the urine concentrating ability
What are the three big things we need to know about ADH?
- increases water permeability in the principal cells of the late distal tubule and collecting ducts via insertion of AQ channels
- increases urea permeability in the IMCD (but not cortical or OMCD)
- Increases activity of the NKCC2 in the thick ascending LOH
The interstitial osmotic gradient is enhanced by what two things?
NaCl and urea
How is the insterstitial gradient initially established?
Salts being actively pumped out by the ascending limb of the LOH makes the entire medullary interstitium salty (hypertonic)
Since the descending limb is only permeable to water, it’s salty for a reason. The water passively leaves the tubule from the descending limb of the LOH
not only is this a major mechanism of gaining water, but the degree of medullary interstitial saltiness will contribute to the ability to make concentrated urine
What is blood Osm?
Filtrate enters PCT at what Osm. and then where does it go?
blood osm. is 300mOsm
Filtrate enters the PCT at 300mOsm and then goes into the descending LOH
Describe water movement in the LOH
the descending LOH is permeable to water
water leaves tubule and enters interstitial space and the remaining solutes within the tubule become more and more concentrated as they descend
As it reaches the base and so much water has left the tubule, the concentration is 1200mOsm
Describe how fluid enters the ascending LOH
since the ascending LOH is only permeable to solutes, NOT water, solutes are pumpled out and the remaining fluid dilutes as it rises
those solutes stay in the interstitial space
This keeps happening until we reach the DCT where the fluid is hypotonic (~100mOsm)
The blood exiting the efferent arteriole and entering the peritubular capillary first passes alongside what?
The ascending loop of Henle
While the fluid in the ascending LOH is heading upward, fluid in the blood vessel is flowing downward (countercurrent)
As blood is flowing through the peritubular capillary near the aLOH, the blood transiently passes through what?
Long card, explaining the countercurrent exchange mechanism of the vasa recta
the interstitial space that is becoming more and more concetrated as the vessel descends
lower concentrated blood picks up solutes that are passing down their gradient from the interstitium to the vessel
as the vessel descends, it becomes more concentrated
at the turn, the blood is concentrated to about 1200mOsm
as the solutes leave interstitium and enter blood, there is more incentive for the aLOH to pump more solutes to replace
as the vessel turns up, it passes alongside the dLOH
As blood ascends, water that is leaving the dLOH will passivley flow into the concentrated BV
blood concentration decreases as it ascends and returns to 300mOsm
What is free water clearance?
what is the eq?
What does it mean if the value is + or -
the difference between water excretion (urine flow rate) and osmolar clearance.
It’s the rate the body excretes solute free water
V=Uosm x V/Posm
When Ch2o is negative: excess solutes are removed, water conserved
When Ch2o is positive: water being excreted, dilute urine formed, water excess
What is osmolar clearance?
The total clearance of solutes from the blood can be expresed as the osmolar clearance.
This is the volume of plasma cleared of solutes each minute, in the same way that clearance of a single substance is calculated.
Cosm=Uosm x V/Posm
What is obligatory urine volume?
What is the Eq?
minimal volume of urine required to excrete waste solutes needing to be excreted from the body
volume is variable depending on daily solute excretory load and the maximum urinary concentration achieveable.
maximal urine concetrating ability in humans is 1200mOsm/L, depending on LOH
OUV=min solute excretion per day/max. urine concentrating ability (1200 in humans)
What is natriuresis?
The excretion of Na in the urine
may be induced by a drug (natriuretic), hormone (ANP), or renal perfusion pressure elevation (pressure natriuresis)
What is diuresis?
large urine output
When the urine primarily contains water, it is called water diuresis, which is in contrast to diuresis seen with the administration of diuretic agents.
Diuretics cause large urine output but with urine that contains solute plus water (solute diuresis)
What is antidiuresis?
When plasma ADH is high, a small volume of concentrated urine is excreted