Lect 11: Loop of Henle

Question 1

The LoH is shaped like a U and it begins at the end of the PT in the cotex and descends as the thin descending limb toward the inner medulla

Answer 1

where it turns 180 degrees and ascends as the thin ascending loop (tALH), back toward the outer medulla, where the tubule epithelia thickens and becomes the thick ascending loop

Question 2

tAL & TAL are IMPERMEABLE TO WATER (but it allows reabsorption of solutes; Na) and the TAL

Answer 2

reabsorbs 25% of the filtered Na. Therefore the TAL dilutes the tubular fluid but reabsorbin Na and Cl w/o reabsorbing water. WATER reabsorption IS NOT FOLLOWING SOLUTE reabsorption HERE. It DILUTES the fluid in the TAL. This decreases the tubular fluid osmolarity below 100mOs/L.
The TAL is called “the diluting segment” for this reason

Question 3

“solute transport engine” refers to

Answer 3

the active Na and Cl reabsorption occurring in the TAL and maintaining a counter-current multiplication of solute concentration difference or solute conc gradient, in the interstitium (not in TF) surrounding the LH and the collecting duct, extending from the cortex to the inner medulla.

Question 4

In addition to the active reabsorption of Na and Cl, another process occurs in the TAL,

Answer 4

2. UREA RECYCLING occurs in the inner medulla also contributes to the solute conc gradient in the interstitium, especially when the need arises to defend against plasma volume depletion (dehydration) &/or hyperosmolarity to excrete conc urine.

UREA recycling occurs when you are dehydrated; this process adds an additional osmotic portential or an additional conc of solute as urea in the inner medulla

Question 5

Thus, osmolaity of the medullary intersititium (outside the tubule!!!!) progressively

Answer 5

incerases upon descending to the inner medulla and can achieve a maximum value in the inner medula varying betw 600-1200mOsm/L which is 2-4 fold the osmolarity of plasma (~300).

600 when you are over-hydrated (bc urea goes away into the interstitium)

1200 when you are under-hydrated
This value depends on the presence or absence of urea

Question 6

in this unique instance, water reabsorption does not follow solute reabsorption and therefore

Answer 6

the epithelia of the TAL effectively dilutes the tubular fluid by reabsorbing Na and Cl w/o reabsorpbing water. This decreases the tubular fluid osmolarity

Question 7

Diuresis

Answer 7

increased excretion of urine with a low osmolarity and low volume

Question 8

Anti-diuresis

Answer 8

increased excretion of urine with a high osmolarity and small volume

Question 9

Reabsorptive solute transport in the TAL is essential for 1.

Answer 9

diluting the tubular fluid osmolarity to values less than plasma thereby excreting a dilute urine when the plasma is expanded or hypo-osmotic

Question 10

Reabsorptive SOLUTE transport in the TAL is essential for 2

Answer 10

concentrating the tubular fluid osmolarity in the collecting duct by maintaining a gradient of interstitial osmolarity driving reabsorption of water from the COLLECTING DUCT back into circulation (not into the TAL) and conc the urine when the plasma volume is contracted and/or hyper-osmotic. The (corticomedullary osmotic) gradient is set up by the thick and thin ascending limb. But the collecting tubule is sensitive to ADH which opens to door to water reabsoprtion in response to this osmotic gradient outside the c.d. Sucks water out of the c.d into the interstitium and into the peritubular capillary and c.d. then into the blood. This is how the collecting duct allows you to retain water in excess of solute when you are dehydrated and you need to defend against volume contraction & hyperosmolarity

Question 11

ADH

Answer 11

=works on the collecting duct top increase its water permeability
=is secreted in response to changes in plasma osmolarity and volume (decr volume, incr osmolarity). it opens the door for water permeability

Question 12

Increased plasma osmolarity

Answer 12

increased ADH secretion and vice versa. ADH incr the water permeability of the collecting duct allowing the osmotic equilibration of tubular fluid with the intersitium and the peritubular vasculature surrounding the collecting duct.

Question 13

in the presence of ADH,

Answer 13

osmotic equilibration of the tubular fluid permits water reabsorption back into circulation and excretion of a conc urine.

Question 14

In the absence of ADH

Answer 14

the collecting duct is impermeable to water preventing water reabsorption and therefore osmotic equilibrium of the tubular fluid with the interstitium and the peritubular vasculature surrounding the collecting duct does NOT oocur, permitting excretion of a dilute urine

Question 15

The osmolarity of the TF in the diluting segment of the nephron (tAL, DCT) is always less than the

Answer 15

that is less than plasma osmolarity in the presence of ADH, regardless of whether volume expanded or contracted (100-120<300). The osmo of the urine that you excrete will depend on the activity of ADH, WHICH MODULATES THE COLLECTING DUCT. (When no ADH present that 100mOsm TF will be excreted as 100mOsm TF urine. When under-hydrated and hv hyperosmotic plasma, ADH is around and that TF changes from 120 to 1200 mOsm due to ADH induced water reabsorption).

Question 16

More water is returned to the plasma (high ADH)

Answer 16

when the plasma volume is contracted or hyperosmotic and less water is returned to the circulation when the plasma volume is expanded and/or hypoosmotic

Question 17

The gradient of osmolarity extending from cortex to inner medulla in the medullary intersititium is always present, in the presence or absence of ADH,

Answer 17

regardles of volume contraction or expansion. But the gradient is less steep in diuresis (volume expanded, decr, plasma osmol) than in antidiuresis (volume contracted, decr)

Question 18

So the controlling variable determining the excretion of a dilute or conc urine is a circulating level of ADH which modulates

Answer 18

the water permeability of the collecting duct and the reabsorption of water from the c.d. back into circulation.

Question 19

Cell physiology of Thin descending loop

Answer 19

• low permeability to solutes (NaCl, urea)
• HIGH WATER PERMEABILITY, so it is concentrating it
• PASSIVE tubular fluid - interstitium equilibration of solute and water concentrates the tubular fluid as it descends into the tDLH this then ascends into the tALH. So at the bottom of the tDLH you have a high conc of NaCl in the TF. Then it turns to enter the tALH.

Question 20

Thin ascending limb

Answer 20

1. passive NaCl reabsorption (outward gradient, losinfgsolute)
2. WATER IMPERMEABLE…so water does not follow…so if you are losing solute in excess of water you are DILUTING the TF.
3. passive urea secretion

Question 21

Thick ascending limb - solute transport engine

Answer 21

• ACTIVE (change from passive) NaCl reabsorption via Na/K/Cl symporter - solute absorbing engine
• relatively water impermeable
• generates and maintains 200mOsm difference in osmolarity between the tubular fluid in the lumen and the interstitium (high) and this transport of solute is multiplies buy a countercurrent process to convert the 200mOs gradient of solute into a 300-1200mOsm gradient in the interstitium.

Question 22

Background: As the TF descends in the thin descending loop, due to its relatively low permeability to solutes and high permeability to water, osmotic equilibration of the TF

Answer 22

with the increasingly hypertonic interstitium results in water reabsorption with little solute reabsorption. ==>progressive conc of Na and Cl in the TF

Question 23

As the TF ascends in the thin ascending limb of LH, passive Na and Cl efflex from the TF occurs (NaCl reabsorption) driven by

Answer 23

high TF Na and Cl conc created by the preceding thin descending limb.
==>tAL is water impermeable so passive efflux of Na and Cl from the TF w/o efflux of water effectovely dilutes and decreases the TF osmolarity in the thin ascending limb

Question 24

In the outer medilla thin becomes thick ascending limb and the transport changes from passive to ACTIVE Na reabsorption. (You reabsorb about 25% of NaCl filterered)

Answer 24

Both thick and thin are impermeable to water and the NaCl reabsorption occurring in the thick dilutes and decreases the TF osmolarity as it advances toward the distal tubule.

Question 25

IMPORTANT: The TAL generates & maintains a 200mOsm difference in osmolarity between the TF in the lumen and intersititium

Answer 25

This function is multiplied by a counter-current process to convert the 200mOs gradient of solute to a 300-1200 gradient in the interstitium

is essential to creating the “counter-current multiplication” of intersititial solute conc and interstitial solute conc gradient extending from cortex to medulla

Question 26

Transport of NaCl Reabsorption in the TAL 1.

Answer 26

Transport for reabsorption of K, Na and Cl at the lumen is a Na-K-Cl symporter.
==>At basolateral side is channels that mediate efflux of intracellular K, Cl (Na uses the Na/K ATPase

Question 27

Transport of NaCl Reabsorption in the TAL 2. Potassium channels

Answer 27

The presence of K channels in the lumenal membrane also mediates efflux of intracellular K back into the TF which together with Cl efflux across the basolateral membrane generates a lumen positive difference across the TAL tubular epithelium.

Question 28

The lumen positive potential difference serves as a driving force for

Answer 28

paracellular Na reabsorption across the TAL epithelium by paracellular diffusion

Question 29

Loop diuretics

Answer 29

inhibits the Na/K/2Cl cotransporter which decreases the reabsorption of Na, k and Cl and increase excretion of Na, k and Cl in the urine and plasma fluid. Solute transport across the TAL generates a 200mOsm gradient across the epithelia from lumen to intersititium

Question 30

Active reabsorption of Na and Cl occuring in the TAL is the solute transport engine.

Answer 30

The TAL reabsorbs or pushes” solute out of the TF against a gradient of 200mOsm, creating a higher osmolarity outside the interstitium.

Question 31

Given the maximum ability of the TAL to pump solute against a gradient of 200mOSm in the outer medulla, what accounts for the 300mOsm to 1200mOsm gradient from cortex to inner medulla achieved during antidiuresis

Answer 31

Answer: The LoH generates and maintains a large corticomedullary osmotic gradient by countercurrent multiplication or amplifying 6x the transport capacity of TAL to pump solute against 200 mOsm difference in translobular osmolarity.

Question 32

Stepwide process begins with the equivalent intersitiial and tubular fluid osmolarities in the descending and ascending limbs.

Answer 32

1. A pumping or reabsorption of solute out of the ascending limb into the interstitium to a limiting osmotic gradient of 200 mOsm and an instant osmoequilibration of the interstitium with the TF in the opposing descending limb
2. An axial advance of isosmotic fluid into the beginning part of the descending limb and exit from the ending part of the ascending limb. Axial advance or a shift of fluid forward along the tubule and instantaneous equilibration of tubular fluid in the descending limb and intersititium

Pump-Equilibration-Shift-Equilibration

Question 33

Countercurrent Multi - Role of Urea Recycling (tubule to interstitium to tubule recycling)

Answer 33

Contributes to the generation and maintainance of an increased cortico-medullary gradient of hyperosmolarity.

Question 34

Urea Recycling

Answer 34

In the outer medulla the interstitial solute osmolarity is due mostly to NaCl, whereas in the deepest parts of the inner medulla, during antidiuresis, approx 50% of the interstitial solute osmoalrity is NaCl and 50% is urea.