Katz: Loop of Henle, Distal Tubule and Cortical Collecting Duct Flashcards
What are juxtamedullary nephrons?
Nephrons that send their loops into the medulla and consist of the descending limb and the thin and THICK ascending limb
What is the difference between the descending limb of the loop of Henle and the ascending limb?
Descending limb- NO net solute transport, just WATER
Ascending limb- no permeability to water, just SOLUTE
What happens to the concentration of solute as it passes through the loop of henle?
Enters from the proximal tubule at 300 mOsms.
At the lowest point it reaches 1400 mOsms.
Enters DCT at 100 mOsms.
What type of cell if found in the TAL?
Big cuboidal epithelial cell
What is the primary transporter in the TAL?
Na/K/2CL co transporter
Moves Na DOWN its gradient while moving K and 2Cl UP the gradient.
Why is the osmolality of the luminal fluid in the TAL only 100 mOsms?
TAL has NO permeability to water. Solutes are transported out while water stays in the tube resulting in a hypo-osmolar solution.
Describe how Na,Cl and K are ultimately reabsorbed in the peritubular capillaries from the TAL?
- Na/K/2Cl co transporter brings them from the lumen into the cuboidal cell of the TAL.
- Na/K ATPase antiporter allows Na to be reabsorbed.
- Cl diffuses through a channel and is reabsorbed.
- K/Cl symporter allows K and Cl to be reabsorbed.
What percent of Na/Cl are reabsorbed in the peritubular capillaries?
20% of the filtered load
What does the export of K into the lumen in the TAL do?
Generates a + lumen that pushes ions like Na, Ca and Mg through tight junctions.
What is Bartter’s syndrome? What does it cause?
Loss of fxn of any of the transport components in the TAL
Salt wasting–> HYPOVOLEMIA
Na/K/2Cl transporters don’t work, leading to the excretion of NaCl and water. This causes the pt to pee a lot, get thirsty and become HYPOvolemic.
What does a loop diuretic do?
Blocks the Na/K/2Cl co transporter in the TAL
What are examples of loop diuretics and what are the good at treating?
Furosemide (lasix)
EDEMA
Most powerful!
Where does luminal fluid move after the loop of Henle? Is it permeable to water?
Early distal tubule
IMPERMEABLE to water
What is the key element in the early distal tubule?
NaCl symporter
Moves Na down it’s gradent while moving Cl up it’s gradient.
What percent of filtered NaCl is reabsorbed here?
5%
What is Gitelman’s syndrome?
Loss of function of the NaCl symporter that leads to SALT wasting.
What drug blocks the NaCl symporter in the early distal tubule?
Thiazide diuretics (HCTZ)
Increase Na, Cl and Water excretion
Thiazide diuretics are useful in treating what conditions? How do they compare to loop diuretics?
HTN- decrease fluid volume> decrease in BP
Only lose 5% vs. 20% so they are MILDER
Where is Na reabsorbed in the nephron?
- PCT- 65%
- TAL- 20%
- DCT- 5%
- CCD- 0-4.9%
- MCD- 5%
What causes variable reabsorption of Na in the CCD?
ALDOSTERONE sensitive PRINCIPLE CELLS in the DCT and CCD
What is the FENa when 4.9% of the filtered lad is reabsorbed in the CCD?
It’s possible to reabsorb 99.9% of total filtered Na so FENa is .1% and Na excretion is only 25 mM/day.
What is the FENa when 0% of the filtered load is reabsorbed in the CCD?
You only reabsorb 95% of the total filtered Na so FENa is 5% and Na excretion is 1250 mM/d.
What does the variable abosrption rate allow for in the CCD?
It allows for Na BALANCE across a wide range of intakes (25- 1,250 mM/d)
What is FENa?
Fraction Excreted Na
What causes a small Na?
Hemorrhage–> lose Na
What is aldosterone and what effects does it have on the late distal tubule and CCD?
A steroid hormone that causes increased TRXN of genes leading to INCREASED expression of luminal Na and K channels as well as basolateral channels and the Na/K pump that leads to INCREASED saving of NaCl.
What happens when aldosterone targets it’s receptor?
Aldosterone enters cytosol> Aldosterone receptor complex translocates to the nucleus> binds specific SREs (steroid response elements)> Increased trxn, trln and INSERTION of: 1.luminal Na (ENaC) 2. K channels 3. Basolateral Na/K pumps > Reabosrb MORE Na
What happens to FENa when more Na is absorbed?
FENa moves towards .1%
What stimulates aldosterone secretion? Where is it secreted from?
LOW Na or HIGH K>
increased aldosterone secretion from adrenal cortical cells (zona glomerulosa)
What leads to an increase in renin?
Low Na diet
hypovolemia (low NaCl/H20)
Low BP> BR reflex> Increased SNS activity
How does low Na lead to an increase in aldosterone?
Low Na> increases renin> Coverts Ang to ANG I> ACE converts Ang I to Ang II> Aldosterone
What is the primary secretion stimulus for aldosterone?
Ang II
What are secondary aldosterone stimuli?
Decrease in plasma Na
Increase in plasma K
Increase in ACTH
What are aldosterones actions?
Increased trxn, trln, insertion of the following channels in PRINCIPLE CELLS:
- Epithelial Na channels (ENaC) and K channels (ROMK)
- Basolateral Na/K pumps and K channels
What are ROMK channels?
Aldosterone sensitive renal outer medullary K channel
How does aldosterone cause Na to be reabsorbed? What happens to K?
Aldosterone> increased ENaC/K channels>
brings Na into cell>
Na/K ATPase allows Na to move into the ISF>
reabsorbed into the peritubular capillaries
K is secreted into the lumen and the ISF.
What is Type I pseudo-hypoaldosteronism?
Loss of function of luminal epithelial Na channels (ENac) in principle cells or collecting duct cells. This leads to SALT WASTING.
What is Liddle’s syndrome?
Gain in fuctionof the ENaC d/t inefficient removal from cell surface (can’t get rid of ENaC)> always reabsorb Na> HTN, Edema, hypevolemia
What is salt sensitive HTN?
Liddle syndroome
Can’t get rid of ENaC channels so you over reabsorb water/Na.
What does Amiloride do?
Blocks ENaC channels.
What leads to an increase in renin?
- Low Na diet/low body NaCL> sensed at JGA via load or delivery signal mediated by macula densa cells
- Hypovolemia> aff arteriolar baroreceptor
- Increased SNS activity
- Low circulating Ang II
What secretes renin?
Granular cells located in the JGA located in the aff arterioles
What are the many actions of Ang II?
- Aldosterone secretion
- VASOCONSTRCITOR
- Na/H exchange to reabsorb more Na
- Vasopressin> reabsorb more water
- Increases SNS activity by Ang II binding to cicumventricular organs
What happens when ang II is too high for a situation?
GROWTH:
LV hypertrophy
Glomerular sclerosis (collapse of glomerular capillaries> decreased GFR)
What are the three mechanisms used to maintain Na balance?
- GFR
- Principal cells and aldosterone
- Proximal Na/H antiporter activity
How does GFR respond to high Na?
Hi Na intake> GFR/filtered load of Na increase> Increase Na EXCRETION.
How does aldosterone respond to high Na?
Hi Na intake> aldosterone levels fall> Na reabsorption falls> Na EXCRETION increases
How does the proximal Na/H antiporter activity respond to high Na intake?
Hi Na intake> renin, angII, NE fall> proximal Na/H antiport activity decreases> Na reabsorption falls> Na excretion increases
How do ANP and BNP help to maintain Na balance?
Both cause increased Na excretion
High salt intake> distension of atria/increased EDV> ANP/BNP secretion increase> aff arteriole dilation/inhibition of renin secretion/direct tubular actions> GFR/filtered load of Na increase> Na reabsorption falls> Na excretion increases
Where do ANP and BNP come from?
ANP- atria
BNP- ventricles
How do you calculate RPF?
Flow in Aff arteriole x plasma Na
How do you calculate the filtered load of Na?
GFR x plasma Na
How do you calculate the concentration of Na in the eff plasma flow?
Eff flow x conc of Na
How do you calculate the Na reabsorptive rate?
Filtered load of Na- Na excretion rate
How do you calculate the Na excretion rate?
Urine flow x urine Na concentration
How do you calculate FENa?
Na excreted/ Total filtered load of Na
How do you calculate Na clearance?
Excretion rate/ concentration of Na in the plasma
