LOH, Distal Tubule and Cortical Collecting Duct Flashcards
What are the two types of nephrons based on LOH size and location? Which do we care about?
justamedullary nephrons and cortical nephrons
we care about juxtamedullary nephrons because their loops dip deep into the medulla
What happens to the extracellular fluid osmolarity as you do deeper into the medulla?
It increases in osmolarity drastically - from 300 mOsm at the corticomedullary junction to nearly 1400 mOsms at the lowest point
How does this increase in osmolarity of the extracellular fluid mean for the function of the descending loop of henle?
It’s primary purpose is for H2O reabsorption - the high osmolarity sucks the water out thorugh aquaporins
Is there also solute movement into the extracellular space from the descending loop of henle?
nope - just water
If there is no solute movement form the descending loop of henle, what happens to the osmolarity inside the loop?
It also goes up drastically - reaching 1400 mOsms in balance at the base
What is the function of the ascending loop in comparison to the descending loop.
In the ascending loop there are channels and pumps for solute movement, but no aquaporins. So here solutes are reabsorbed, but water isn’t
What’s the new pump found on the luminal membrane of the ascending limb of the LOH?
the Na+/K/2Cl co-transporter
What happens to the Na+ that’s pumped into the cell by the Na+/K/2Cl co-transporter?
It’s pumped out to the extracellular fluid via the Na/K atpase
What happens to the K+ that’s pumped into the cell by the Na+/K/2Cl co-transporter
It builds up and then gets either pumped into the extracellular fluid with the K+Cl- symporter or some leaks back into the luminal fluid via a K channel
What happens to the 2 Cl_ that are pumped into the cell by the Na+/K/2Cl co-transporter
Some of it goes into the extracellular fluid via the K+/Cl- symporter and some diffuses down its concentration gradient via Cl channels
There is another way for Na+ to get to the extracellular fluid from the lumen in the ascending limb. How?
Goes through tight junctions (remember that the Na+, K+ and 2 Cl- balance the charge transport through the cotransporter, but some K+ leaks back into the lumen, making the lumen a bit too positively charged for Na+’s liking.)
What percentage of NaCl filtered load is reabsorbed in the ascending limb?
about 20%
What happens to the osmolarity of the extracellular fluid outside of the ascending loop?
What happens to the osmolarity of the filtrate inside the ascending loop?
the osmolarity increases in the extracellular fluid because there’s only solute reabsorption and no H2O reabsorbtion
the osmolarity of the filtrate goes down because of the same reason
What is the osmolarity of the filtrate once you reach the top of the ascending loop?
only 100 mOsms
Loss of function of any transport component in the ascending limb will result in what syndrome/
Bartter’s syndrome
What happens in Bartter’s syndrome?
salt wasting - you don’t get salt reabsorbtion, so you excrete too much Na and Cl. Water follows solute so you also have diuresis and hypovolemia
What drug will essentially cause a Bartter’s syndrome/
loop diuretics = furosemide or bumetanide
What is the brand new transporter in the early distal convoluted tubule/
the luminal NaCl symporter
uses secondary active transport with Na moving down it’s concentration gradient and bringing Cl with it
What blocks the luminal NaCl symporter in the early distal convoluted tubule?
thiazide diuretics
Loss of function of the NaCl symporter causes what syndrome? Symptoms?
Gitelman’s syndrome?
salt wasting and hypovolemia - but not nearly as bad as Bartter’s syndrome because only 5% of NaCl is reabsorbed here instead of the 20% from the ascending limb
Moving on to the late distal convoluted tubule and the cortical collecting duct….How much Na is reasbored there?
It’s variable! Ranges from 0 to 4.9%
How is Na+ reabsorbtion in the cortical collecting duct regulated?
aldosterone-sensitive principal cells are located in this area
aldosterone promotes Na reabsorbtion
If the range of Fractional Excretion of Na ranges from 0.1% to 5%), and a total filtered load of Na being 25,000 mM/day, what is the normal range of Na excreted in the urine?
25 mM/day to 1250 mM/day
used to keep us in Na balance. If we eat a lot of sodium, Aldosterone release goes down and we excrete more sodium
About how much Na is reabsorbed from the medullray collecting duct?
about 5%
Where is aldosterone secreted from?
the adrenal cortical cells = zona glomerulosa
What are the triggers for aldosterone secretion?
low sodium or high potassium
also angiotensin II, which is increased when renin is released (triggered by low Na+, hypovolemia or increased sympathetic nervous system)
How does aldosterone work?
it’s a steroid, so it binds to the receptor and the aldosterone receptor complex translocates to the nucleus and binds to steroid response elements on the DNA to increase transcription, translation and insertion of necessary channels and transporters
What channels and transporters are increased with aldosterone?
- luminal Na+ channels (ENaC)
- luminal K channels
- basolateral Na/K ATPases
- basolateral K channels
What is the name of the aldosterone-sensitive luminal K channels?
the renal outer medullary K channel = ROMK
What happens in Type 1 pseudo-hypoaldosteronism?
it’s loss of function of the luminal ENaCs in the principal cells. This means you don’t get Na reabsorbion and you have salt wasting and hypovolemia
What happens in Liddle’s syndrome?
An issue with transporter trafficking where the cell can put ENaCs up when aldosterone is high, but it can’t receycle them away frm the membrane when aldosterone is low, so you just constantly reabsorb salt
you get salt-sensitive hypertension, hypervolemia and edema
What are the triggers for Renin release from the juxtamedullary cells of the afferent arteriole? There are 4…
- low Na+ sensed at the juxtamedullary apparatus
- hypovolemia sensed at the afferent arteriolar baroreceptors (the juxtamedullary cells again)
- high symapthetic nerve activity (induced by other baroreceptors from hypovolemia)
- low circulating angiotensin II
What are the 5 things angiotensin II does?
- stimulates aldosterone secretion
- vasoconstrictor
- proximal Na+/H+ exchange to reabsorb more Na+
- Vasopressin release to increase H2O reabsorption
- increases sympathetic nervous activity
ultimately, it wants to save salt, save water, save volume and save BP
If angiotensin II is too high for the situation, what happens?
it starts to act like a growth factor, specifically, you get left ventricular hypertrophy and glomerular sclerosis
What happens to GFR as salt intake increases?
it also increases - higher salt means high plasma volume, which means higher pressure in the glomerulus with higher GFR and higher creatinine clearance
What happens to Na excretion with increased salt intake? How about serum sodium concentration?
excretion increases, but serum concentration actually doesn’t change that much = Na balance!
What happens to body weight with increased slat intake?
increases - because extracellular fluid volume increases (edema)
What happens to renin activity with increast salt intake?
decreased
What happens to plasma aldosteron with increased salt intake?
decreased
What happens to systolic and diastolic BP with increased salt intake?
nothing much at all - so sodium doesn’t have much effect on epople who don’t have HTN or salt-sensitivity
Does intracellular fluid go up with increased NaCl intake?
nope - remember - Na/KATPase
So…what are the four major renal mechanisms to stay in Na+ balance?
- GFR and hence the filtered load of Na+ - will increase with increased salt intake
- principal cells have aldosterone directed increases in Na+ reabsorption
- Proximal Na/H antiporer activity increases in direct responseto renin-angiotensin system and sympathetic nerves or NE
- ANP and BNP cause increased Na excretion (dilates afferent arteirole to increase GFR and filtered load of Na)
