Session 3 Renal Physiology

Question 1

In the early PCT, what are the ions doing?

Answer 1

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

Question 2

How much of each thing is reabsorbed in the PCT?

Na, K, water

NaHCO

Glucose and Amino Acids

Answer 2

65%

85%

~100% (that’s why its bad when you see protein and sugar in someone’s urine)

Question 3

Na Bicarb reabsorption in the PCT is initated by what?

Answer 3

Na/H exchanger located in luminal membrane of the PCT epithelial cell

Question 4

What does carbonic anhydrase do?

Answer 4

forms H2CO3 from CO2 and water

which then breaks down into H and Bicarb to be used later in important things

Question 5

In all portions of the nephron, Na is pumped into the interstitium to maintian low intracellular Na. How is this done?

Answer 5

Na/K ATPase in the basolateral membrane pumps the reabsorbed Na into the interstitium

Question 6

In the straight/late Proximal Tubule, acid secretory systems secrete what into where?

Answer 6

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

Question 7

Clinical Application: Inhibition of carbonic anhydrase does what?

Answer 7

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

Question 8

What is happening in the thin limb of the loop of Henle?

Answer 8

water is reabsorbed from the thin limb into the blood

it is water permeable and impermeable to ions/solutes

Question 9

What is happening at the thick ascending limb of the loop of henle?

Answer 9

reabsorbs Na (25%) and is impermeable to water

Question 10

What is going on with NaCl around the thick ascending limb of the LOH

Answer 10

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

Question 11

The NKCC2 cotransporter increases intracellular K which leaads to what?

Answer 11

back diffusion of K into tubular lumen, allowing a lumen positive electrical potential to drive reabsorption of cations (Mg and Ca) via paracellular pathway.

Question 12

Clinical Applications: inhibition of the NKCC2 cotransporter by loop diuretics in the thick ascending LOH causes what?

Answer 12

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

Question 13

What is happening at the DCT?

Answer 13

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)

Question 14

Clinical Applications at the DCT by inhibition of Na/Cl tranporter by what compound does what?

Answer 14

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

Question 15

What is going on at the Collecting Duct?

Answer 15

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

Question 16

How does aldosterone affect the collecting duct?

Answer 16

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

Question 17

How does ADH affect the collecting duct?

Answer 17

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

Question 18

In the absence of ADH, cortical collecting tubule and collecting duct is impermeable to what?

Answer 18

water and dilute urine is produced as a result

(water can’t get out so urine is really water, less salty)

Question 19

ETOH decreases ADH release and has what effect?

Answer 19

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

Question 20

Clincial Application functioning at the collecting duct

Essentially same result, just two ways to go about it.

Answer 20

Two types for K sparing diuretics

1. 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
2. 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

Question 21

Add Tables after watching lecture if needed

Question 22

Normally, Na is secreted or reabsorbed where depending on needs?

Answer 22

Na is secreted or reabsorbed in the late Distal Tubule and cortical Collecting Duct

Question 23

What are the most important factors that stimulate Na reabsorption?

What are the most important factors that stimulate Na secretion?

Answer 23

Na deficiency, low Na diet, hyponatremia

Na loss through SEVERE diarrhea

angiotensin II

aldosterone

1. increased Na conc. in ECF
2. increased tubular flow rate

Question 24

K is secreted or reabsorbed where?

Most important factors that stimulate K reabsorption?

Most important factors that stimulate K secretion?

Answer 24

in the late Distal Tubule and cortical collecting duct

• K deficiency, low K diet, hypokalemia
• K loss through SEVERE diarrhea

1. increased ECF K conc.
2. aldosterone
3. increased tubular flow rate
4. Na delivery to cortical CD

Question 25

How do the principal cells in the CD become permeable to water?

Answer 25

ADH inserts AQ2 channels into the membrane

Question 26

Describe urea permeability in the inner medullary collecting ducts?

Answer 26

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.

Question 27

Describe the NKCC2 in the Thick Ascending Loop of Henle

Answer 27

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

Question 28

What are the three big things we need to know about ADH?

Answer 28

1. increases water permeability in the principal cells of the late distal tubule and collecting ducts via insertion of AQ channels
2. increases urea permeability in the IMCD (but not cortical or OMCD)
3. Increases activity of the NKCC2 in the thick ascending LOH

Question 29

The interstitial osmotic gradient is enhanced by what two things?

Answer 29

NaCl and urea

“salty medulla”

Question 30

How is the insterstitial gradient initially established?

Answer 30

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

Question 31

What is blood Osm?

Filtrate enters PCT at what Osm. and then where does it go?

Answer 31

blood osm. is 300mOsm

Filtrate enters the PCT at 300mOsm and then goes into the descending LOH

Question 32

Describe water movement in the LOH

Answer 32

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

Question 33

Describe how fluid enters the ascending LOH

Answer 33

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)

Question 34

The blood exiting the efferent arteriole and entering the peritubular capillary first passes alongside what?

Answer 34

The ascending loop of Henle

While the fluid in the ascending LOH is heading upward, fluid in the blood vessel is flowing downward (countercurrent)

Question 35

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

Answer 35

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

Question 36

What is free water clearance?

what is the eq?

What does it mean if the value is + or -

Answer 36

the difference between water excretion (urine flow rate) and osmolar clearance.

It’s the rate the body excretes solute free water

Ch2o=V-Cosm

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

Question 37

What is osmolar clearance?

Answer 37

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

Question 38

What is obligatory urine volume?

What is the Eq?

Answer 38

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)

Question 39

What is natriuresis?

Answer 39

The excretion of Na in the urine

may be induced by a drug (natriuretic), hormone (ANP), or renal perfusion pressure elevation (pressure natriuresis)

Question 40

What is diuresis?

Answer 40

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)

Question 41

What is antidiuresis?

Answer 41

When plasma ADH is high, a small volume of concentrated urine is excreted