6: Basic Renal Processes for Sodium, Chloride, and Water Flashcards
If you give a patient a hypertonic saline bolus, how does this affect its intracellular osmolality?
increases
water will shift from IC space to the EC due to the osmotic pull from the hypertonic saline in the IV space
If your patient has hemorrhagic gastroenteritis will large volume of vomiting and diarrhea, how does this affect its intracellular osmolality
Increases
vomitus and diarrhea is hypotonic - left-over osmoles increase the IV and interstitial osmolality and pull water from the IC space
If you give your patient a D5W infusion, how does this affect its IC volume?
increases - water will distribute evenly through IC and EC space
What percentages of sodium are rabsorbed in the proximal tubule, the loop of Henle and the distal convoluted tubules?
- 65%
- 25%
- 10%
compared to the filtered sodium load, what percentage remains in the final urine?
less than 1%
What are the major anions absorbed with sodium in the tubules to maintain electroneutrality?
- Chloride
- Bicarbonate
Where is most bicarbonate reabsorbed?
In the proximal tubules (90%)
What are the two sources of body water?
- water intake (drinking/eating)
- water production during carbohydrate oxidation
What are the 4 ways of bodily water loss?
- urination
- gastrointestinal losses
- exhalation
- skin evaporation
Is the luminal or basolateral membrane of tubular cells more permeable to water?
basolateral membrane
high number of aquaporines –> cytosolic osmolality close to that of the interstitium
describe the luminal water permeability of tubular cells in the following nephron segments:
* proximal tubules
* loop of Henle
* distal convoluted tubules
* collecting ducts
- 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
What does obligatory water loss mean?
the minimum water needed to excrete sufficient amounts of urea, sulfate, phosphate, and other waste products
Why does starvation decrease one’s ability to survive without water?
- 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
How is most Na reabsorbed on the apical/tubular side of the poximal tubular cells?
via the NHE-3 antiporter
Sodium-hydrogen-exchanger 3
Name 3 solutes that are reabsorbed in the proximal tubules and are sharing a symporter with Na
- Amino acids
- glucose
- phosphorous
How does Na exit the cell on the basolateral tubular cell membrane?
Na-K-ATPase
Na/HCO3- symporter
Explain how Chloride is reabsorbed in the proximal tubules
- Cl/Base antiporter on luminal membrane and Cl-channel + K-Cl symporters on basolateral membrane
- paracellular through tight junctions
Fill the gaps
Explain how organic bases and H+ protons are recycled in the poximal tubules
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
What percentage of water and and NaCl are reabsorbed in the loop of Henle?
25% of filtered NaCl
10% of filtered water
What is the Na concentration of tubular fluid at the end of the loop of Henle?
1/3 of plasma –> ~ 50 mEq/L
What parts of the Loop of Henle expresses aquaporins?
Only the descending limb
How are Cl and Na reabsorbed in the THIN ascending loop of Henle?
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
How are Cl and Na reabsorbed in the THICK ascending loop of Henle?
- 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)
Where does the thick ascending limb of the loop of Henle start?
at the junction between inner and outer medulla
Where does the aldosterone-sensitive part of the nephron start?
second half of the distal convoluted tubule
How do the distal convoluted tubules further dilute the tubular fluid?
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
What class of diuretics work in the distal convoluted tubules
Thiazide diuretics
Where in the nephron do the principal and intercalated cells start and what is their proportion?
connecting tubule
70% principal cells - rest intercalated
What is the main task of principal versus intercalated cells?
principal cells - water and Na reabsorption
intercalated cells - Cl, K, acid/base transport
What is the tubular and interstitial osmolality in the cortical collecting ducts?
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)
What percentage of the filtered water load reaches the collecting ducts?
25%
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
- Na-H-antiporter (65%)
- Na-K-2Cl symporter (25%)
- Na-Cl symporter (5%)
- eNaCs (5%)
How does ADH increase luminal water permeability?
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
What solutes achieve the high medullary interstitial osmolality?
Na and urea - about half each (Na really just a quarter but accompanied by anion for electroneutraly –> Na x 2 = osmolality contribution)
How high does the medullary interstitial osmolality get?
As high as 1400 mOsm/kg
Explained how the high Na concentration in the medullary interstitium is achieved
- 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
Other than making the collecting duct more permeable to water, how does ADH affect water reabsorption?
- 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
Explain how the high urea concentration in the medullary interstitium is achieved
- 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)
Explain the medullary washout
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
