Loop of Henle, Distal tubule, and Collecting Duct Flashcards
What are the 3 distinct parts of the Loop of Henle?
- Thin Descending Limb
- Thin Ascending Limb
- Thick Ascending Limb
What are the general functions of the LOH and Distal Tubule (DT)?
LOH:
• Counter current multiplication
• Active Transport of NaCl (25% reabsorption)
DT:
• Regulated on Reabsorption of NaCl (5% reabsorption)
Compare Filtrate to Blood Plasma as it leaves the following locations: • Glomerulus • Proximal Tubule • Loop of Henle • Distal Tubule
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
What is the first segment of the distal tubule?
• what happens here
- Loop of Henle - specifically the descending limb.
* Urine is CONCENTRATED from 280 mOsmol/Kg to 1200 mOsmol
Descending Loop of Henle
• Cellular Structure/Location
• What happens here
• How does it happen?
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
Does Na+ transport play a role in concentrating the urine in the Descending LOH?
• if so how?
• How does water move during this process?
NO, Na+ plays no role in concentrating urine here
• water moves through AQUAPORINS to interstium
How much does the osmolarity of fluid increase while in the Descending Loop of Henle?
• what molecules drive this osmotic gradient?
280 mOsmol to 1200 mOsmol
•Urea and NaCl are responsible for this high concentration in the interstitium (600 mOsmol each)
Thin ascending limb of Loop of Henle
• Cellular Structure/Location
• What happens here
• How does it happen?
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
What Helps to maintain the gradient as fluid ascends up the ascending LOH?
Urea maintains gradient because it remains impearmeable to the tubule despite the gradual reduction in NaCl.
Thick Ascending Limb
• Cellular Structure/Location
• What happens here
• How does it happen?
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
Why is it necessary to have so much active transport in the thick ascending limb?
• Active Transport needed because the Tubular Filtrate is Isotonic with the environment by the time it reaches the Thick ascending loop of Henle.
T or F: the N-K-Cl transporter transports molecules down the electrochemical gradient
True
***Note: this transporter is also known as NK2C
How do loop diuretics work?
• Where do they work?
• Name 2.
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
What is the Condition of Diuresis?
• What causes it?
Arginine Vasopressin (AVP) and antidiuretic Hormone (ADH) stimulate NK2C and stimulate NaCl reabsorption causing: • Increased Fluid Retention
T or F: loop diuretics are more effective than others.
True
Distal Convoluted Tubule and Collecting Duct
• Structure
• General Function
• Water Permeability
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
T or F: while the cellular make up and origin of the DCT and CD are very different their functions are very similar
True.
What does ADH do to your urine?
Causes urine to become Hyperosmotic
How much of the original components are left in the Filtrate by the time it gets to the distal tubule?
• 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
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?
- ENaC = Electrically Conductive Sodium Channels
• One Sodium at a Time is driven through the channel via Electrochemical Gradient
**Present in Both DCT and CD - Na-Cl co-transporter
* *ONLY in Distal Convoluted Tubule
What ultimately drives ENaC?
Na+/K+ ATPase (NKA) in the BASOLATERAL MEMBRANE
What drugs act on ENaC?
• where anatomically do they act?
ENaC is located in both the collecting duct AND distal convoluted tubule
Drugs:
• Amiloride
• Triamterene
What drugs act on the Na-Cl co-transporter?
• where anatomically does this act?
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
How do the ENaC channels play a role in K secretion?
• does this play a bigger role in DCT or CD?
- 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
Where does K+ excretion occur?
• Driving Forces?
• (natural) Regulating Factors?
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
T or F: Loop Diuretics are 10 times as effective as diruretics such as Amiloride, Triamterene, and Thiazide Diruretics.
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
What is the Effect of the Following on K+ excretion?
• Loop Diuretics
• Thiazide Diuretics
• Amilorides, Triameterene
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
What is the effect of ALDOSTERONE?
• mechanism?
• Where does it work?
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
What genes does Aldosterone act to upregulate?
- 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
Describe how Addison’s Disease affects kidney function.
- 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*
What is Conn’s Syndrome?
• What is the effect on Kidney Function?
***Opposite of Addison’s
- Tumors Release Excess Aldosterone
- INCREASE Na+ Reabsorption occurs
*Less than 0.2% of filtered Load of Na+ is excreted
What is Liddle Syndrome?
• What is the effect on Kidney Function?
***Same effect as Conn’s but different mechanism
- ENaC mutation prevents it from being degraded
- INCREASE Na+ Reabsorption occurs
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?
- Principle Cells
• work in Na+ REABSORPTION and K+ SECRETION - Intercalated Cells
• PROTON secretion (Some also secrete bicarbonate)
How does the Epithelium in the DCT and CD differ from that in the Proximal Tubule?
• 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
Describe the Process of Normal Proton Transport in the DCT and CD under Normal conditions and Acidic conditions.
• Driving Forces?
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
Describe the Process of Normal Proton Transport in the DCT and CD in alkalosis.
• Driving Forces?
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)
Under conditions of Alkylosis are Alpha or Beta cells for active in the DCT and CD?
Beta cells because you need to secete HCO3- into the lumen and retain H+
