Renal Handling of Na, CL, Water Week 2 Flashcards
Explain filtration, secreiton and reabsorption of water and Na Cl
Freely Filtered
Almost entirely reabsorbed
No secretion
Generalization about Na Cl H2O
FIRST : Na+ reaborption is mainly active through the transcellular routeand powered by the Na-K-ATPase (on the basolateral membrane).
SECOND : Cl- reaborption is passive (paracellular) and active (transcellular).Regardless of route, it is directly or indirectly linked to Na+ reaborption. In most cases, parallel Cl- reabsorption is implied when describing Na+ reaborption.
THIRD : H20 reaborption is by osmosis and is secondary to reabsorption of solutes, particularly Na+ and those dependent on Na+ reabsorption.
What is the main pathwway of Na+ excretion> What are others?
HOw much of ingested Na+ do we excrete
Main is urine although we lose 10mM through feces and 10mM through sweat. We excrete about 80% of digested Na+ through urine. BUt this still means that 99% is reabsorbed
Break down of salt reabsorption in parts of nephron
Proximal- 65%
Descending- none
Ascending- 25%
Distal- 5%
CD- 4-5%
Lose about 1% in urine– not that since so much is filtered that a small change in reasbroption can make a large change in the mount excreted.
Explain Cl- reabsoprtion
What does it follow?
Na+- this is bcause of the electronegativity rule. For any volume the number of anions has to equal cations. For any volume of fluid (no membranes separating things here), the fluid will contain equal numbers of anions and cations. In our case, if the filtrate contains ~140 mEq of Na+ then it will also contain ~140 mEq of anions.
Cl reasbsorption
Proximal- 65
How many Cl- routes of transport are there in the proximal tubule
explain them
- Paracellular throught the not so tight, tight junctions down it’s electrochemical gradient
- Transcellular- uses energy stores in Na+ gradient to move Cl- into the apical membrane and once in the cell it can move out the basolateral side(facilitated with K+) down it’s gradient
Body’s response to low water intak
High water intake
Your body’s response to drinking a large volume of water is to produce a large volume of dilute urine. Dilute here means urine with an osmolarity less than that of plasma. To do this, the kidneys excrete water in excess of salt. Your body’s response to drinking too little water is to produce a small volume of concentrated urine.
Concentrated means urine with an osmolarity more than that of plasma. To do this, the kidneys excrete salt in excess of water.
Two sources of body water
how can we lose water
Food/drink and metabolically produced water.
Lost via GI tract, skin, lungs and kidney.
Skin/lungs(insensible water loss because you are usually not aware of it)
Break down of water reabsoprtion
proximal tubule-65% (just like Na+
L of H Descending- 10% (Na at ascending at 25%) more Na+ than water
Dital tubule- No water (5% Na+)
CD- 4-25%
Ways that water is transported
- Down its osmotic gradient
2, aMay dffuse through the bilayer
- May difuse through tight junctions
How quickly it moves depends on A. the size of the gradient B. The relative H20 permeability of different pathways
Explain the difference in permeability in basolateral and apical
Basolateral through the whole nephonr is highly permeable to water because of the presence of aquaporins
Apical Membrane tight junction permeability Varies
- Proximal and Descending are highly permeable to H20
- Ascending and Distal are NOT permeable to H20
- Tight Junctions of CD also NOT permeable ut can’t be regulated
Explain Obligatory water loss
- The kidney can produce urine concentrated up to 1400mmoles/L almost 5x the plasma concentrtation.
- We have to excrete about 600mmoles/day of solute urea
- So the minimal concentration is 600/1400 ~.43L/day- so we have a minimal loss of .43L of water in urine a day
*** this number may vary- fasting may result in some tissue catabolism releasing excess solute that must be excreted and thus this would increase the obligatory water loss.
Why can’t we drink sea water
Sea water has 2400mml/L so it would take 2400/1400 1.7 L
Minimun urine osmalality– 50 mmol
Average osmalitly 500-800 mmol
Fasting/overnight osmalality- 900mmol/L
Explain Na+ reabsoprtion at the proximal tubule
Changes in CL, HCO3, GLucose and AA osmolarity
1, At the beginning the Na-H-antiporter moves Na+ into the cell and H+ out.
- HCO3- follows, this isn’t actulally filtered bicrab but what is reformed int he cell– since it’s reasbrobed HCO3 levels drop alon the length of proximal tubule
- Cl- rise intially because it is HCO3 that leaves with Na+ for electronegativity and since water is leaving, Cl- osmolarity increases. — eventually when HCO3 levels drop Cl- follows Na+ and will drop as well
- The proximal tubule is highly H2O permeable. Thus, even a tiny trans-tubular osmotic gradient is sufficient to drive H2O out of the proximal tubule. Indeed, 65% of filtered water is reabsorbed from the proximal tubule in exactly this situation. Fluid reasorbing locally lowers tubule osmolarity and increases interstitum an this is enough for water to follow through the tight junctions.
Explain iso osmotic volume reasborptoin
the volume of the tubular fluid decreases but its overall osmolarity remains relatively constant. The point here is that every little bit of solute reabsorbed drives a little bit of H2O to be reabsorbed. The result is that, at each point along the proximal tubule, nearly equal proportions of solute and H2O are reabsorbed
Hence why Na+ has a straight unchanging line for osmolarity in the proximal tubule although it is heavily reabsorbed. It’s the most abundant solute so it mirros tubular fluid
Explain osmotic diursis
An increase in urine flow—-An osmotic diuresis occurs when the tubular fluid contains a substantial amount of solute that is either incompletely reabsorbed or not reabsorbed at all. The presence of this extra “trapped” solute increases the osmolarity of the tubular fluid and retards H2O reabsorption from the proximal tubule (and in more distal regions of the nephron as well).
Like in diabetics they have glucose that is not reabsorbed so water follows causing osmotic diurtic
Like in mannitol which works to reduce intracranial pressure- it is filtered but not reabsorbed so increases urine and decrease extracellular fluid volume and termpoarilty reduces cranial pressure
Explain difference in water and Na+ in the loop of Henle
what does this meanf or the tubular osmolarity
Unlike the proximal tubule, the loop of Henle (over its entire length) always reabsorbs proportionally more Na+ (~25% of its filtered load) than H2O (~10% of its filtered load). Thus, the fluid leaving the loop is always more dilute (hypo-osmotic) compared to the fluid entering it.
H20 is in descending- The H2O reabsorption that occurs in the descending limb concentrates lumenal fluid and this favors the passive Na+ reabsorption in the thin ascending limb of the loop (probably via the paracellular route).
Na+ is in the ascendng- passive in thin and active in thick
Explain the transport of Na+ at the thick ascening loop
- Active Na/K= pump at the basolateral
- Secondary from energy stored in gradient uses Na/K/Cl at the apical membrane
3, This apical is a targer of loop diuretic like furosemid or lasix
IN order the Na?K/2Cl to work all three need to present so there is an apical channel for K+ to reenter the lumen to be cycled back out
Since it only absorbs Na+ (no h20)at the ascening loop the end product is hypo-osmotic to the plasma
Explain the distal convuluted tubule Na+
imperable to water and reabsorbs 5% of Na+
- Active Na/K pump as basolateral
- Na/Cl symporter pump at apical that uses Na+ gradient- seconday transort
- This Na/Cl symporter is blocked by thiazide drus
- THe apical membrane of the distal also has Ca2+ channels that are controlled by parathyroid hormone
Is the distal diluting or concentration segment
Diluting- it reabsorbs Na but not water so it make tube more hypoosmotic compared to water and delivers that to the collecting duct
Explain the two cell types in the CD
Principle- handle H20 and Na+
Intercalated handle Cl- and acid base balance
Explain the steps of Na+ reabsorbed in the CD
- Na/K pump in the basolateral
- Na+ apical channel (different from those in muscles and nerves)
- These channels can be blocked by amiloride TTX
These Na+ channels on the apical CD membrane are regulated by aldosteron
Usualy water permeability is very low in the CD bt under hormonal control of ADH
What are 4 important facts about ADH
- Normal permeabilti to water
- Inner medulla changes
- Is it all or non
- What does it do
- Normally water has low permeability at the CD and is hormonal rgulated/increased by ADH
- The CD in the inner most medulla has some permeability even in the complete asbanse of ADH so some water is always absorbed there
- ADH is not all or none. Add low ADH we increase water permeability by a little
- ADH triggers mirgration of intracellulr vesciesl to the apical membrane- aquaporin channels that increase permeability- when ADH is gone these channels are withdrawn with endocytosis
What happens when there is no ADH
The filtrate enter is hypo osmotic so with no ADH there is no water reabsorption and it will reamin hypoosmtic in the cortex and outter medulla. IN the inner medulla there is finite reabsoprtion of water bcause of the hyperostomic interstitum but overall H20 reabsorbed is too little to change the hypoosmotic urine
What happens when ADH is present
Water is rapidly reabsorbed from the hypoosmotic fluid in the cortical CD because here the intersittum is like te plasma so there is a osmotic driving force. Water moves until iso osmotic with the interstitum. As it moves down the medulla more water is reabsorbed because the medulla is so hyper osmotic
So with ADH we have a low volume of concentration (hyperosmotic) urine
3 essentials in creating the high osmalrity of the medulla
- The active Na+ reabsorption by the thick ascending limb of loop of Henle.— remember the thick ascending Loop reabsrobs Na+ but no water so it is dilutingthe tube while concentrating the interstitum. It also has the Na/K/Cl symporter and if this is completley blocked we lose osmoalarity gradient of the medulla
- The unique arrangement of peritubular capillaries (vasa recta) in medulla. - medulla has slower blood flow which allows solute to accumulate. Doesn’t cause the gradient but helps to presevrve it. Also the countercurrent exchange (next card)
- The recycling of urea between collecting duct and loop of Henle.
Explain how the loop struture of vasa recta and how it helps maintain medulla high osmolarity. What’s it called?
Vasa recta are like a loop so
- Blood descending becomes hyperosmotic-loses water to medulla
- As it comes back up it returns backt o it’s orginial
This is called the countercurrent exchange system
Exlpain the urea cycle
- Freely filtered in BC then 50% reabsorbed at proximal, then about same as the 50% is secreted at the loop. It stays like that until the inner medulla of the CD where about 50% can be reabsorbed.
When we need to conserve water the permeability of CD is high and urea becomes highly concentrated and potentially could create a driving force for reasbroptino of urea.
When we are over hydrated, H20 permeabilty of CD is low and tubular flow is fast and urea concentration will not rise before it reaches the inner medulla CD. Some urea can be reabsorbed if tubular concentration is ghigher than intersititum but in CD it can only be secreted if lower than that in the interstitum.
