Renal Handling of Na, CL, Water Week 2

Question 1

Explain filtration, secreiton and reabsorption of water and Na Cl

Answer 1

Freely Filtered

Almost entirely reabsorbed

No secretion

Question 2

Generalization about Na Cl H2O

Answer 2

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.

Question 3

What is the main pathwway of Na+ excretion> What are others?

HOw much of ingested Na+ do we excrete

Answer 3

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

Question 4

Break down of salt reabsorption in parts of nephron

Answer 4

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.

Question 5

Explain Cl- reabsoprtion

What does it follow?

Answer 5

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

Question 6

How many Cl- routes of transport are there in the proximal tubule

explain them

Answer 6

1. Paracellular throught the not so tight, tight junctions down it’s electrochemical gradient
2. 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

Question 7

Body’s response to low water intak

High water intake

Answer 7

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.

Question 8

Two sources of body water

how can we lose water

Answer 8

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)

Question 9

Break down of water reabsoprtion

Answer 9

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%

Question 10

Ways that water is transported

Answer 10

1. Down its osmotic gradient

2, aMay dffuse through the bilayer

3. 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

Question 11

Explain the difference in permeability in basolateral and apical

Answer 11

Basolateral through the whole nephonr is highly permeable to water because of the presence of aquaporins

Apical Membrane tight junction permeability Varies

1. Proximal and Descending are highly permeable to H20
2. Ascending and Distal are NOT permeable to H20
3. Tight Junctions of CD also NOT permeable ut can’t be regulated

Question 12

Explain Obligatory water loss

Answer 12

1. The kidney can produce urine concentrated up to 1400mmoles/L almost 5x the plasma concentrtation.
2. We have to excrete about 600mmoles/day of solute urea
3. 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.

Question 13

Why can’t we drink sea water

Answer 13

Sea water has 2400mml/L so it would take 2400/1400 1.7 L

Question 14

Minimun urine osmalality– 50 mmol

Average osmalitly 500-800 mmol

Fasting/overnight osmalality- 900mmol/L

Question 15

Explain Na+ reabsoprtion at the proximal tubule

Changes in CL, HCO3, GLucose and AA osmolarity

Answer 15

1, At the beginning the Na-H-antiporter moves Na+ into the cell and H+ out.

2. 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
3. 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
4. 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.

Question 16

Explain iso osmotic volume reasborptoin

Answer 16

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

Question 17

Explain osmotic diursis

Answer 17

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

Question 18

Explain difference in water and Na+ in the loop of Henle

what does this meanf or the tubular osmolarity

Answer 18

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

Question 19

Explain the transport of Na+ at the thick ascening loop

Answer 19

1. Active Na/K= pump at the basolateral
2. 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

Question 20

Explain the distal convuluted tubule Na+

Answer 20

imperable to water and reabsorbs 5% of Na+

1. Active Na/K pump as basolateral
2. Na/Cl symporter pump at apical that uses Na+ gradient- seconday transort
3. This Na/Cl symporter is blocked by thiazide drus
4. THe apical membrane of the distal also has Ca2+ channels that are controlled by parathyroid hormone

Question 21

Is the distal diluting or concentration segment

Answer 21

Diluting- it reabsorbs Na but not water so it make tube more hypoosmotic compared to water and delivers that to the collecting duct

Question 22

Explain the two cell types in the CD

Answer 22

Principle- handle H20 and Na+

Intercalated handle Cl- and acid base balance

Question 23

Explain the steps of Na+ reabsorbed in the CD

Answer 23

1. Na/K pump in the basolateral
2. Na+ apical channel (different from those in muscles and nerves)
3. 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

Question 24

What are 4 important facts about ADH

1. Normal permeabilti to water
2. Inner medulla changes
3. Is it all or non
4. What does it do

Answer 24

1. Normally water has low permeability at the CD and is hormonal rgulated/increased by ADH
2. The CD in the inner most medulla has some permeability even in the complete asbanse of ADH so some water is always absorbed there
3. ADH is not all or none. Add low ADH we increase water permeability by a little
4. 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

Question 25

What happens when there is no ADH

Answer 25

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

Question 26

What happens when ADH is present

Answer 26

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

Question 27

3 essentials in creating the high osmalrity of the medulla

Answer 27

1. 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
2. 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)
3. The recycling of urea between collecting duct and loop of Henle.

Question 28

Explain how the loop struture of vasa recta and how it helps maintain medulla high osmolarity. What’s it called?

Answer 28

Vasa recta are like a loop so

1. Blood descending becomes hyperosmotic-loses water to medulla
2. As it comes back up it returns backt o it’s orginial

This is called the countercurrent exchange system

Question 29

Exlpain the urea cycle

Answer 29

1. 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.