L41 | Renal Water Balance

Describe the mechanism of action of vasopressin and where it acts

• Vasopressin increases water reabsorption in the kidney by making the collecting duct more permeable to water.

• Vasopressin (ADH) acts on V2 receptors in the collecting duct to insert aquaporin-2 channels

Explain how the properties (physical juxtaposition, placement in the renal medulla, and transport characteristics) of the ascending and descending limbs of the loops of Henle allow them to contribute to producing a concentrated urine

• The loop of Henle can concentrate urine because:

  • limbs sit right next to each other and flow opposite directions (countercurrent)

    • This layout allows each limb to influence the other, multiplying small differences in osmolarity into a large osmotic gradient—the countercurrent multiplier.

  • They run deep into the high-osmolarity medulla

    • Because the loop is physically located in this gradient, it can:

    • (1) Pull water out of the descending limb (where water can move)

    • (2) Pump salt out of the ascending limb (where salt can move)

  • The descending limb loses water, and the ascending limb pumps out salt

    • Ascending limb pumps salt out → makes medulla hyperosmotic

    • Descending limb loses water → fluid becomes concentrated

• Together, these characteristics generate the medullary osmotic gradient needed to produce concentrated urine.

• _______________ → urine flow above usual levels

• _______________ → urine flow below usual levels (hyperosmotic urine)

• diuresis → urine flow above usual levels

• antidiuresis → urine flow below usual levels (hyperosmotic urine)

_________ → detect plasma osmorality

Osmoreceptors → detect plasma osmorality

When osmolarity increases, ADH ______________ to conserve water.

When osmolarity increases, ADH secretion increases to conserve water.

Low arterial pressure → _________ baroreceptor firing → __________ ADH secretion

Low arterial pressure → decrease baroreceptor firing → increase ADH secretion (more water reabsorption)

Sweat is a _______________ solution, meaning it has ______ water than solutes

Sweat is a hypoosmotic solution, meaning it has more water than solutes

Sweating removes dilute fluid (hypoosmotic), causing ECFV to ____________ and the osmolarity of body fluids ___________

Sweating removes dilute fluid (hypoosmotic), causing ECFV to decrease and the osmolarity of body fluids increase

What are the mechanisms by which the kidneys respond to sweating to decrease excretion of both salt and water

After sweating, the kidneys conserve water via ADH and conserve salt via RAAS (renin → angiotensin II → aldosterone), while reducing GFR to minimize both water and Na⁺ loss.

Compare the stimuli for thirst with the stimuli for vasopressin secretion

Both thirst and ADH (vasopressin) are triggered by ↑ osmolarity and ↓ blood volume

An _________ in angiotensin II can stimulate thirst

An increase in angiotensin II can stimulate thirst

The body regulates the loss of water mainly through __________

The body regulates the loss of water mainly through urine

Because output of water is greater than input during prolonged heavy exercise, your body increases its ___________ to consume more water

Because output of water is greater than input during prolonged heavy exercise, your body increases its thirst to consume more water

T/F: Kidney’s control of H₂O excretion is dependant on Na+, K+, urea

False; Kidney’s control H₂O excretion independently of Na+, K+, urea

____________ is always open and present in the membranes for H₂O to be permeable for nephrons

AQP1 is always open and present in the membranes for H₂O to be permeable for nephrons

Where is water permeable when ADH is low?

• proximal tubule

• thin descending limb of Henle

Where is water permeable when ADH is high?

• proximal tubule

• thin descending limb of Henle

• collecting duct 

• Hypoosmotic urine → more _______________

• Hyperosmotic urine → more _______________

• Hypoosmotic urine → more diluted

• Hyperosmotic urine → more concentrated

What are the requirements for production of concentrated urine? Why does it work?

• (1) Hyperosmotic medullary interstitium

  • Serves as osmotic equilibrating device

• (2) antidiuretic hormone (ADH =AVP)

  • ADH dependent water channels, AQP2

  • Passive reabsorption of water by osmosis

• Why it works?

  • descending loop of Henle is not permeable to solutes, but permeable to H₂O

  • ascending loop of Henle is not permeable to H₂O, but permeable to solutes

What causes concentrated urine?

High ADH → AQP2 insertion → collecting duct becomes water-permeable → water leaves tubule via osmosis into salty medulla → concentrated urine.

How does urine become diluted?

Urine becomes dilute as it moves through ascending limb of loop of Henle due to Na⁺ reabsorption & H₂O impermeability

What are the stimuli for ADH release?

• osmoreceptors

• baroreceptos

What makes the collecting duct water-permeable?

ADH makes the collecting duct water-permeable by inserting AQP2 channels into the luminal membrane so water can leave the tubular fluid and be reabsorbed.

1. ADH travels in the blood and binds to V₂ receptors on the basolateral membrane of collecting duct cells (side facing interstitial fluid/blood).

2. Binding of ADH activates Adenylate Cyclase, converting ATP → cAMP, which activates Protein Kinase A (PKA).

3. PKA causes phosphorylation of proteins → vesicles containing AQP2 channels move and fuse with the apical (luminal) membrane. AQP2 is the only regulated aquaporin.

4. Now that AQP2 is inserted, water moves down its osmotic gradient from the urine in the lumen → into the collecting duct cell.

5. On the basolateral membrane, AQP3 and AQP4 are always present and open (not regulated by ADH). Water exits the cell through these channels into the interstitial fluid → blood.

AQP2 is regulated by ______________

AQP2 is regulated by ADH

With ADH → AQP2 inserted → water reabsorbed → ____________ urine

With ADH → AQP2 inserted → water reabsorbed → concentrated urine

What is the flow of water through the collecting duct to be reabsorbed back into the blood?

Tubular lumen → AQP2 → inside cell → AQP3/4 → interstitial fluid/blood

_________ and ___________ are always present, located on the basolateral membrane, but are not regulated by ADH

AQP3 and AQP4 are always present, located on the basolateral membrane, but are not regulated by ADH

What are the tubular actions of ADH?

• o   (1) AVP/ADH binds V₂ receptor

  • basolateral membrane

• o   (2) Insert Aquaporin 2 – (AQP2)

  • luminal membrane

___________ and/or _____________ require antidiuresis 

Water restriction and/or severe sweating require antidiuresis 

____________ requires diuresis

high water intake requires diuresis

_____________ are the most important stimulus for thirst under most physiological conditions

Osmoreceptors are the most important stimulus for thirst under most physiological conditions

Why severe sweating triggers ADH release through two different pathways? (How does your body defend against dehydration?)

• Osmoreceptor Pathway

  • increase plasma osmolarity

  • increase ADH

  • decrease water excretion

• Baroreceptor Pathway

  • decrease plasma volume

  • increase ADH

  • decrease water excretion