Loop of Henle, Distal Tubule and Collecting Duct - Muster Flashcards
What is the role of isolated solute reabsorption in the loop of henle?
-
Reabsorbes ~25% of the filtered Na+
- Na+ is reabsorbed in excess of water
- only descending limb is permeable to H2O
What are the basic transporters in the loope of henle?
- Descending limb:
- permeable to water (gets peed out)
- Thin/Thick Ascending limb:
- Not permeable to water, No aquaporins!
- reabsorb a TON of solute
- Lumenal side:
- NKCC Pump!
- K+ channel (recycling)
- Basolateral side:
- K+/Cl- Symporter
- Cl- channel
- Na+/K+ ATPase
- Not permeable to water, No aquaporins!
What’s so special about this NKCC Pump?
- Located in thick ascending limb of loop of henle
- Secondary active transport of Na+, K+, and 2Cl- into cell
- Uses energy from Na+ going down gradient
- all spots of pump must be occupied for it to work
- Chloride is rate limiting, high affinity for Na+ & K+
- Reabsorbs ~20% of the filtered load of sodium
What are the basic transporters of the Distal Tubule?
- Lumenal side:
- Na+/Cl- symporter
- Basolateral side:
- Na+/K+ ATPase
- K+ channel (recycling)
- Cl- channel
What are the basic transporters of the collecting duct?
- Principal cell
- Lumenal side:
- Epithelial Na+ channel (ENac)
- sodium in cell
- Renal Outer Medullary K+ channel (ROMK)
- potassium out of cell
- Epithelial Na+ channel (ENac)
- Basolateral side:
- Na+/K+ ATPase
- K+ channel
- Lumenal side:
- Intercalated cell
What is the hormonal regulation of sodium reabsorption in the collecting duct?
- Aldosterone
- stimulated by Angiotensin II
- is lipophilic, so it enters principal cell
- binds to Steroid Response Element (SRE) receptor => increase transcription, translation, and insertion of:
- basolateral Na+/K+ ATPase
- luminal ENac
- luminal ROMK
- causes increased Na+ reabsorption & K+ secretion
- controls ~2% of filtered Na+
What solute conditions stimulate the release of Aldosterone?
- Low Na+
- High K+
What disease is due to a genetic mutation of any of the transporters in the thick ascending loop of henle (NKCC, Potassium recycling channel, K/Cl symporter, Chloride channel, or Sodium/Potassium ATPase)?
Bartter syndrome
- growth retardation/mental retardation
- volume depletion
- low BP
- Hypokalemia
- metabolic alkalosis
- elevated urine calcium
What disease is due to a genetic mutation of the NaCl symporter in the distal tubule?
Gitleman Syndrome
- Metabolic alkalosis
- Hypocalciuria
- Hypomagnesemia
- Hypokalemia
- Normal BP
- Not as severe as Bartter syndrome
What disease is due to dysfunction of the ENac in the collecting duct?
- Increased ENac
- Always on constantly reabsorbing Na+
- Liddle’s Syndrome
- causes HTN
- pseudohyperaldosteronism
- Decreased ENac
- loss of fxn
- Type 1 pseudohypoaldosteronism
What signaling pathways cause Renin release in the kidney?
(Hint: 3 stimuli)
- Sympathetic Input (NE)
- Decreased stretch in afferent arteiole
- Decreased Sodium/Chloride delivery to the Macula Densa
***All trigger release of renin from Juxtaglomerular cells in granular cells of afferent arterioles!
What are the actions of Angiotensin II on sodium reabsorption?
- Stimulates Aldosterone
- upregulates ENac
- Stimulates Proximal Tubule reabsorption of Na+
What are the effects of varied sodium intake on:
- GFR
- Filtered load of Na+
- Blood pressure
- Renin & Aldosterone levels
- GFR (creatinine clearance)
- High salt => increased filtered load of Na+
- Na+ excretion increases
- Renin
- regulates Na+/H+ antiporter in prox. tubule
- High salt => reduced renin => reduced Na+ reabsorption
- Na+ excretion increases
- Aldosterone
- stimulated by low salt states
- High salt => reduced Aldosterone
- fewer ENaC channels to reabsorb Na+
- Na+ excretion increases
What is the relative reabsorption of sodium for each segment of the nephron?
- Proximal Tubule = 65%
- Loop of Henle (Thick ascending part) = 25%
- Distal Tubule = 5%
- Collecting Duct = variable 0% to ~5%
