6: Basic Renal Processes for Sodium, Chloride, and Water

Question 1

If you give a patient a hypertonic saline bolus, how does this affect its intracellular osmolality?

Answer 1

increases

water will shift from IC space to the EC due to the osmotic pull from the hypertonic saline in the IV space

Question 2

If your patient has hemorrhagic gastroenteritis will large volume of vomiting and diarrhea, how does this affect its intracellular osmolality

Answer 2

Increases

vomitus and diarrhea is hypotonic - left-over osmoles increase the IV and interstitial osmolality and pull water from the IC space

Question 3

If you give your patient a D5W infusion, how does this affect its IC volume?

Answer 3

increases - water will distribute evenly through IC and EC space

Question 4

What percentages of sodium are rabsorbed in the proximal tubule, the loop of Henle and the distal convoluted tubules?

Answer 4

• 65%
• 25%
• 10%

Question 5

compared to the filtered sodium load, what percentage remains in the final urine?

Answer 5

less than 1%

Question 6

What are the major anions absorbed with sodium in the tubules to maintain electroneutrality?

Answer 6

• Chloride
• Bicarbonate

Question 7

Where is most bicarbonate reabsorbed?

Answer 7

In the proximal tubules (90%)

Question 8

What are the two sources of body water?

Answer 8

• water intake (drinking/eating)
• water production during carbohydrate oxidation

Question 9

What are the 4 ways of bodily water loss?

Answer 9

• urination
• gastrointestinal losses
• exhalation
• skin evaporation

Question 10

Is the luminal or basolateral membrane of tubular cells more permeable to water?

Answer 10

basolateral membrane
high number of aquaporines –> cytosolic osmolality close to that of the interstitium

Question 11

describe the luminal water permeability of tubular cells in the following nephron segments:
* proximal tubules
* loop of Henle
* distal convoluted tubules
* collecting ducts

Answer 11

• proximal tubules - highly water permeable with aquaporines and permeable tight junctions - reabsorption here is isotonic
• descending thin loop of Henle early parts still very permeabel to water
• ascending thick loop of Henle relatively water impermeable - higher Na than water fraction reabsorbed –> tubular fluid leaving here will be hypotonic (osmolality 1/3 of plasma)
• distal convoluted tubules little to no water reabsorption/very low permeability
• collecting ducts permeability is highly variable and adjusted depending on body water status

Question 12

What does obligatory water loss mean?

Answer 12

the minimum water needed to excrete sufficient amounts of urea, sulfate, phosphate, and other waste products

Question 13

Why does starvation decrease one’s ability to survive without water?

Answer 13

• starvation leads to a catabolic state –> releases excess solutes and waste products –> increases the obligatory water loss
• If no food intake –> no water production from carbohydrate oxidation
• no protein intake –> not enough urea to achieve sufficient osmolality of the inner medullary interstitium

Question 14

How is most Na reabsorbed on the apical/tubular side of the poximal tubular cells?

Answer 14

via the NHE-3 antiporter
Sodium-hydrogen-exchanger 3

Question 15

Name 3 solutes that are reabsorbed in the proximal tubules and are sharing a symporter with Na

Answer 15

• Amino acids
• glucose
• phosphorous

Question 16

How does Na exit the cell on the basolateral tubular cell membrane?

Answer 16

Na-K-ATPase
Na/HCO3- symporter

Question 17

Explain how Chloride is reabsorbed in the proximal tubules

Answer 17

• Cl/Base antiporter on luminal membrane and Cl-channel + K-Cl symporters on basolateral membrane
• paracellular through tight junctions

Question 18

Fill the gaps

Answer 18

Question 19

Explain how organic bases and H+ protons are recycled in the poximal tubules

Answer 19

Hydrogen ions leave the tubular cells in exchange for Na entering (NHE-3 antiporter)

Base leaves the tubular cell in exchange for a Cl- ion entering (antiporter)

The H+ and base can then unite and are able to diffuse into the cell as Hbase –> will split in the cell and are able to facilitate further Na and Cl absorption

Question 20

What percentage of water and and NaCl are reabsorbed in the loop of Henle?

Answer 20

25% of filtered NaCl
10% of filtered water

Question 21

What is the Na concentration of tubular fluid at the end of the loop of Henle?

Answer 21

1/3 of plasma –> ~ 50 mEq/L

Question 22

What parts of the Loop of Henle expresses aquaporins?

Answer 22

Only the descending limb

Question 23

How are Cl and Na reabsorbed in the THIN ascending loop of Henle?

Answer 23

tubular fluid has a higher Na and Cl concentration because of water reabsorption in the descending limb –> creates concentration gradient favoring absorption

Cl is absorbed via Cl channels on both apical and basolateral membranes

Na follows paracellularly through tight junctions

Question 24

How are Cl and Na reabsorbed in the THICK ascending loop of Henle?

Answer 24

• Na-K-ATPase on baselateral side –> creating concentration gradient for Na flux (like everywhere)
• Na-K-2Cl symporter –> apical membrane –> movement into cell
• to prevent K depletion in the tubular fluid - K channel moves K down cc gradient out of the cell back into the lumen (K recycling)
• Cl exits on the basolateral side via Cl channels and K-Cl symporter
• paracellular Na movement achieves electroneutrality (otherwise too much Cl- would be absorbed alone)

Question 25

Where does the thick ascending limb of the loop of Henle start?

Answer 25

at the junction between inner and outer medulla

Question 26

Where does the aldosterone-sensitive part of the nephron start?

Answer 26

second half of the distal convoluted tubule

Question 27

How do the distal convoluted tubules further dilute the tubular fluid?

Answer 27

NaCl reabsorption with little water absorption * basolateral Na-K-ATPase * luminal Na-Cl symporter * luminnal electrogenic sodium channels * K and Cl leave on the basolateral side via individual channels + K-Cl symporter

Question 28

What class of diuretics work in the distal convoluted tubules

Answer 28

Thiazide diuretics

Question 29

Where in the nephron do the principal and intercalated cells start and what is their proportion?

Answer 29

connecting tubule 70% principal cells - rest intercalated

Question 30

What is the main task of principal versus intercalated cells?

Answer 30

principal cells - water and Na reabsorption intercalated cells - Cl, K, acid/base transport

Question 31

What is the tubular and interstitial osmolality in the cortical collecting ducts?

Answer 31

interstitium in cortical region always same osmolality as plasma (high blood flow, i.e., ~ 300 mOsm/kg) tubular osmolality low because of preceeding diluting segments (~ 100 mOsm/kg)

Question 32

What percentage of the filtered water load reaches the collecting ducts?

Answer 32

25%

Question 33

Give the primary Na transporter or channel for these segments (give percentage of total Na reabsorption for each) * proximal tubule * thick ascending limb of the loop of Henle * distal convoluted tubule * collecting duct

Answer 33

* Na-H-antiporter (65%) * Na-K-2Cl symporter (25%) * Na-Cl symporter (5%) * eNaCs (5%)

Question 34

How does ADH increase luminal water permeability?

Answer 34

ADH binds to the vasopressin type 2 receptors --> activates adenylate cyclase --> catalyzes intracellular cAMP production --> induces migration of intracellular vesicles containing aquaporin 2 to the luminal membrane aquaporin 2 will be removed by endocytosis if ADH is absent

Question 35

What solutes achieve the high medullary interstitial osmolality?

Answer 35

Na and urea - about half each (Na really just a quarter but accompanied by anion for electroneutraly --> Na x 2 = osmolality contribution)

Question 36

How high does the medullary interstitial osmolality get?

Answer 36

As high as 1400 mOsm/kg

Question 37

Explained how the high Na concentration in the medullary interstitium is achieved

Answer 37

* thick ascending loop of Henle absorbs NaCl (NaK2Cl symporter) at higher magnitude than thin descending loop absorbs water --> deposits hyperosmolar fluid in the interstitium * vasa recta in medulla - parallel blood vessels with slower blood supply --> don't remove solutes from medullary interstitium as effectively as in the cortex * countercurrent exchange of the vasa recta: ascending vasa recta with fenestrations and ability to diffuse solutes back into the descending vessel --> prevents loss of solutes

Question 38

Other than making the collecting duct more permeable to water, how does ADH affect water reabsorption?

Answer 38

* ADH increase will cause vasoconstriction of the vasa recta (by constricting the pericytes surroung descending vasa recta) --> even slower blood flow --> medullary interstitial osmolality can increase even more * ADH raises urea permeability in the inner medullary collecting ducts (ADH-sensitive isoforms of urea uniporters) --> increases medullary osmotic gradient further

Question 39

Explain how the high urea concentration in the medullary interstitium is achieved

Answer 39

* all urea freely filtered * proximal tubule: 50% reabsorbed * descending thin loop of Henle --> 50% urea gets back into tubular fluid (coming from high medullary interstitial cc) --> restores AMOUNT but cc keeps going up because of almost all water being reabsrobed until reach medullary collecting ducts (50x plasma cc) * inner medullary collecting ducts --> half urea absorbed through urea uniporters (driven by high tubular to interstitial cc gradient)

Question 40

Explain the medullary washout

Answer 40

overhydration --> less ADH --> less cortical and outer medullary collecting duct water reabsorption --> tubular fluid does not get as concentrated by the time it reached the inner medullary collecting duct ---> urea concentration gradient does not cause urea reabsorption or even causes secretion + high internstitial osmolality causes much of the excess water to be reabsorbed --> diluting the interstitium