Loop of Henle, Distal tubule, and Collecting Duct

Question 1

What are the 3 distinct parts of the Loop of Henle?

Answer 1

• Thin Descending Limb
• Thin Ascending Limb
• Thick Ascending Limb

Question 2

What are the general functions of the LOH and Distal Tubule (DT)?

Answer 2

LOH:
• Counter current multiplication
• Active Transport of NaCl (25% reabsorption)

DT:
• Regulated on Reabsorption of NaCl (5% reabsorption)

Question 3

Compare Filtrate to Blood Plasma as it leaves the following locations: 
• Glomerulus
• Proximal Tubule 
• Loop of Henle
• Distal Tubule

Answer 3

Leaving Glomerulus:
• Same as Plasma minus Proteins

Leaving Proximal Tubule:
• Same as Plasma minus NUTRIENTS and proteins

Leaving LOH and DT:
• Markedly different from Plasma

Question 4

What is the first segment of the distal tubule?

• what happens here

Answer 4

• Loop of Henle - specifically the descending limb.

* Urine is CONCENTRATED from 280 mOsmol/Kg to 1200 mOsmol

Question 5

Descending Loop of Henle
• Cellular Structure/Location
• What happens here
• How does it happen?

Answer 5

Cellular Structure/Location:
• Epithelial cells with few mitochondria - IMPERMEABLE TO ions (Na+ etc)
• Extends from Cortex to Outer Medulla

What Happens:
• Concentration of the Urine

How does it Happen:
• INTERSTITIAL FLUID towards medulla is HYPEROSMOTIC to FILTRATE
• H2O moves out of Tubule to interstitium down its osmotic gradient

Question 6

Does Na+ transport play a role in concentrating the urine in the Descending LOH?
• if so how?
• How does water move during this process?

Answer 6

NO, Na+ plays no role in concentrating urine here

• water moves through AQUAPORINS to interstium

Question 7

How much does the osmolarity of fluid increase while in the Descending Loop of Henle?
• what molecules drive this osmotic gradient?

Answer 7

280 mOsmol to 1200 mOsmol

•Urea and NaCl are responsible for this high concentration in the interstitium (600 mOsmol each)

Question 8

Thin ascending limb of Loop of Henle
• Cellular Structure/Location
• What happens here
• How does it happen?

Answer 8

Cellular Structure/Location:
• Epithelial cells with few mitochrondria but they are IMPERMEABLE to H2O

What Happens:
• Sodium Reabsorption (25%)

How Does it Happen:
• Insanely concentrated fluid from descending loop of Henle goes up the ascending loop of Henle
•Instead of H2O diffusing back in as the fluid goes into increasing HYPOsmotic environments IONS (NaCl) diffuse OUT into interstitium

***Again overall driving force is the osmotic gradient

Question 9

What Helps to maintain the gradient as fluid ascends up the ascending LOH?

Answer 9

Urea maintains gradient because it remains impearmeable to the tubule despite the gradual reduction in NaCl.

Question 10

Thick Ascending Limb
• Cellular Structure/Location
• What happens here
• How does it happen?

Answer 10

Cellular Structure/Location:
• THICK epithelial cells with MANY mitochondria
• IMPERMEABLE TO WATER (like descending limb)

What Happens:
• MORE Na+ Reabsorbtion (5%)

How does it Happen:
• LUMINAL: Na-K-Cl transporter pumps INTO the cell 1 Na, 1 K, and 2 Cl.
**note: this is an electrically neutral transfer

• BASOLATERAL MEMBRANE: Na/K ATPase Pumps Na+ out to Renal Interstitium

Question 11

Why is it necessary to have so much active transport in the thick ascending limb?

Answer 11

• Active Transport needed because the Tubular Filtrate is Isotonic with the environment by the time it reaches the Thick ascending loop of Henle.

Question 12

T or F: the N-K-Cl transporter transports molecules down the electrochemical gradient

Answer 12

True

***Note: this transporter is also known as NK2C

Question 13

How do loop diuretics work?
• Where do they work?
• Name 2.

Answer 13

Furosemide and Bumetanide

MOA:
• BLOCKAGE of Cl- binding site on NK2C (Na-K-2Cl co-transporter)

• Blocking of this site prevents the additional sodium excretion that happens in the THICK ASCENDING LIMB

*While the Thick Ascending LOH is impermeable to H2O the salt will still be in the lumen and will draw in water at a later time

Question 14

What is the Condition of Diuresis?

• What causes it?

Answer 14

Arginine Vasopressin (AVP) and antidiuretic Hormone (ADH) stimulate NK2C and stimulate NaCl reabsorption causing: 
• Increased Fluid Retention

Question 15

T or F: loop diuretics are more effective than others.

Answer 15

True

Question 16

Distal Convoluted Tubule and Collecting Duct
• Structure
• General Function
• Water Permeability

Answer 16

Structure:
• Thick ascending LOH gives rise to a DISTAL CONVOLUTED TUBULE
• 6-8 DCTs form a Collecting Duct
• CDs join to make a Duct of Bellini

General Function:
• Dilution of Tubular Filtrate (via differential absorption and secretion of ions)

Water Permeability:
• VARIABLE permeability to Water!!
•This is because ADH acts on DCTs to increase water permeability via AQP-2

Note: increased permeability here would tend to allow water to flow out

Question 17

T or F: while the cellular make up and origin of the DCT and CD are very different their functions are very similar

Answer 17

True.

Question 18

What does ADH do to your urine?

Answer 18

Causes urine to become Hyperosmotic

Question 19

How much of the original components are left in the Filtrate by the time it gets to the distal tubule?

Answer 19

• Receives ~10% of H2O, less than 10% NaCl and KCl, and 50% urea

• Na+ is actively Reabsorbed
• K+ is Secreted
• Na+ reabsorption is greater than K+ secretion so Cl- is also Reabsorbed

Question 20

What are the two distinct mechanisms for Sodium Reabsorption in Distal Convoluted Tubule and Collecting Duct?
• are either of the mechanisms specific to only that area?

Answer 20

1. ENaC = Electrically Conductive Sodium Channels
   • One Sodium at a Time is driven through the channel via Electrochemical Gradient
   **Present in Both DCT and CD
2. Na-Cl co-transporter
   * *ONLY in Distal Convoluted Tubule

Question 21

What ultimately drives ENaC?

Answer 21

Na+/K+ ATPase (NKA) in the BASOLATERAL MEMBRANE

Question 22

What drugs act on ENaC?

• where anatomically do they act?

Answer 22

ENaC is located in both the collecting duct AND distal convoluted tubule

Drugs:
• Amiloride
• Triamterene

Question 23

What drugs act on the Na-Cl co-transporter?

• where anatomically does this act?

Answer 23

Thaizide Diuretics block the Na-Cl co-transporter
• Block Na reabsorption resulting in delivery of more fluid into the distal nephron and more fluid excretion or diuresis

• Act ONLY in Distal Convoluted Tubule

Question 24

How do the ENaC channels play a role in K secretion?

• does this play a bigger role in DCT or CD?

Answer 24

• There is a NEGATIVE VOLTAGE existing in the lumen due to the ENaC channels.
• As Na+ is pulled through the ENaC channels the lumen becomes more negative and the membrane Depolarizes
• Depolarization leads to the Ejection of K+ from the cell INTO the LUMEN

More Important in Collecting Duct

Question 25

Where does K+ excretion occur? • Driving Forces? • (natural) Regulating Factors?

Answer 25

Distal Convoluted Tubule and Collecting Duct Driving Forces: • High Intracellular [K+] • Lumen-negative Voltage Regulating Factors: • Increased Na+ will increase lumen-negative voltage • HIGHER FLUID FLOW also leads to more K+ secretion

Question 26

T or F: Loop Diuretics are 10 times as effective as diruretics such as Amiloride, Triamterene, and Thiazide Diruretics.

Answer 26

True, Remember Loop Diruretics (Furosemide and bumetanide) work in the Thick Ascending Loop of Henle to block Na+ reabsorption Amiloride and Triameterene - Block ENaC and prevent Na+ uptake in DCT and CD Thiazide Diuretics - Block Na-Cl co-transporter in DCT and CD

Question 27

What is the Effect of the Following on K+ excretion? • Loop Diuretics • Thiazide Diuretics • Amilorides, Triameterene

Answer 27

***All K+ effects manifested in DCT or CD*** ``` Loop Diuretics (working in TALOH): • Increase Na+ and flow • Result: more Na+ in the Lumen leads to more Na+ flowing down ENaC and MORE K+ SECRETION (via membrane depol.) into the lumen of DCT and CD ``` Thiazide Diuretics: • Block Na-Cl Electro-neutral Na+ transport • NO EFFECT ON DEPOLARIZATION because both Na+ and Cl- are transferred into the cell • ONLY K+ secretion comes from inc. Flow Amilorides and Triameterene: • Block ENaC • PREVENTION OF DEPOLARIZATION occuring because Na+ is not being transported into epithelium to allow for more Neg. Lumen potential and Positive Cell Potential • DECREASES K+ secretion

Question 28

What is the effect of ALDOSTERONE? • mechanism? • Where does it work?

Answer 28

Aldosterone: • Increases Na+ REABSORPTION and K+ SECRETION MECHANISM: • MINERALCORTICOSTEROID so it diffuses through the adrenal cortex • Bind to Nuclear Receptors to regulate gene expression of Genes related to Na Reabsorption WHERE: • ONLY works in DCT and CD

Question 29

What genes does Aldosterone act to upregulate?

Answer 29

* ENaC * Na-Cl co-transporter * NKA (Na+/K+ ATPase) * K+ Channels **Also increases expression of Kreb's Cycle Enzymes and ATP synth** ALL these factors act to inc. Na+ absorption and K+ secretion

Question 30

Describe how Addison's Disease affects kidney function.

Answer 30

* COMPLETE absence of Aldosterone Production * No Aldosterone = LESS Na+ Reabsorption and increased NaCl excretion in urine ***Nearly 2% of Filtered load of NaCl is excreted in these Pts****

Question 31

What is Conn's Syndrome? | • What is the effect on Kidney Function?

Answer 31

***Opposite of Addison's * Tumors Release Excess Aldosterone * INCREASE Na+ Reabsorption occurs ***Less than 0.2% of filtered Load of Na+ is excreted**

Question 32

What is Liddle Syndrome? | • What is the effect on Kidney Function?

Answer 32

***Same effect as Conn's but different mechanism * ENaC mutation prevents it from being degraded * INCREASE Na+ Reabsorption occurs

Question 33

What cell types are essential in Acidification of the Urine in DCT and CD? • In general what task is performed by these different cell types?

Answer 33

1. Principle Cells • work in Na+ REABSORPTION and K+ SECRETION 2. Intercalated Cells • PROTON secretion (Some also secrete bicarbonate)

Question 34

How does the Epithelium in the DCT and CD differ from that in the Proximal Tubule?

Answer 34

• It is IMPERMEABLE to DIFFUSION (PT is permeable) * pH in lumen = 4.5 * pH in Cytoplasm = 7.4 ****Different from proximal tubules in that there is a 800 fold greater H+ concentration in the tubular fluid****

Question 35

Describe the Process of Normal Proton Transport in the DCT and CD under Normal conditions and Acidic conditions. • Driving Forces?

Answer 35

Apical Side: • ATP hydrolysis Drives transport of H+ from cell to lumen through apical Channel • Channel = H+K+-ATPase aka Proton Pump Basolateral: • Increased HCO3- (via H2CO3 dissociation to get the H+) leads to HCO3- exchange for Cl- on basolateral membrane ***Under Acidic conditions cells will express a new H+ transporter***

Question 36

Describe the Process of Normal Proton Transport in the DCT and CD in alkalosis. • Driving Forces?

Answer 36

Proton Pump is switched from Apical Side to Basolateral Side HCO3-/Cl- exchanger is switched to Lumenal Side ***Note: in reality this is not a switch within the same cell*** * ALPHA cells (proton pump is on the lumenal side) * BETA cells (proton pump in on the basolateral side)

Question 37

Under conditions of Alkylosis are Alpha or Beta cells for active in the DCT and CD?

Answer 37

Beta cells because you need to secete HCO3- into the lumen and retain H+