Lecture 12: Renal III Aspects of Renal Water Excretion and Conservation

Why is creatinine always expected in urine?

because 100% of filtered creatinine is excreted

Water intake sources

the water we drink and food we eat

What do we lose fluid to?

- Metabolic production

- Insensible loss and sweat

- The bulk of fluid loss is from urine and fecal waste

Why do we need to concentrate urine?

Humans are not surrounded by water at all times therefore we need to conserve water, we can do so by concentrating urine.

The longer the loop of Henle,

the more concentrated urine is

2 types of nephrons

cortical (85%)

juxtamedullary (15%)

Countercurrent mechanism

Occurs when fluid flows in opposite directions in two adjacent segments of same tube with hair pin turn

Countercurrent multiplier

interaction of filtrate flow in ascending/descending limbs of nephron loops of juxtamedullary nephrons

- Multiply the osmolality within the loop of Henle

Countercurrent exchanger

blood flow in ascending/descending limbs of vasa recta

Role of countercurrent mechanisms

- Establish and maintain osmotic gradient (300 mOsm to 1200 mOsm) from renal cortex through medulla

- Allow kidneys to vary urine concentration

Loop of Henle: descending limb

- Freely permeable to H2O

- H2O passes out of filtrate into hyperosmotic medullary interstitial fluid

- Filtrate osmolality increases to ~1200 mOsm

Loop of Henle: ascending limb

- Impermeable to H2O

- Selectively permeable to solutes

- Filtrate osmolality decreases to 100 mOsm

Solute permeability of ascending

Na+ and Cl- actively reabsorbed in thick segment; some passively reabsorbed in thin segment

What region of nephrons creates the osmotic gradient?

Long nephron loops of juxtamedullary nephrons

The countercurrent multiplier depends on which three properties of the nephron loop to establish the osmotic gradient.

- Fluid flows in opposite directions (countercurrent) through two adjacent parallel sections of a nephron loop.

- The descending limb is permeable to water, but not to salt.

- The ascending limb is impermeable to water, and pumps out salt.

There is a constant ___mOsm difference between the two limbs of nephron loop and between the ascending limb and interstitial fluid

200mOsm

Countercurrent multiplier and mOsm difference

difference is usually 200mOsm and gets 'multiplied' along length of loop to ~900mOsm

As water and solutes are reabsorbed, what does the nephron loop do?

it first concentrates the filtrate and then dilutes

Passage of filtrate through nephron loop - step 1

Filtrate entering the nephron loop is isosmotic to both blood plasma and cortical interstitial fluid.

Passage of filtrate through nephron loop - step 2

Water moves out of the filtrate in the descending limb down its osmotic gradient.

This concentrates the Filtrate.

Passage of filtrate through nephron loop - step 3

Filtrate reaches its highest concentration at the bend of the loop.

Passage of filtrate through nephron loop - step 4

Na+ and Cl- are pumped out of the filtrate. This increases the interstitial fluid osmolality.

Passage of filtrate through nephron loop - step 5

Filtrate is at its most dilute as it leaves the nephron loop. At 100 mOsm, it is hypoosmotic to the interstitial fluid.

Role of countercurrent exchanger

Preserve medullary gradient

- Prevent rapid removal of salt from interstitial space

- Remove reabsorbed water

Where is the countercurrent exchanger located?

vasa recta

From where does water enter the ascending vasa recta?

- Descending vasa recta

- reabsorbed from nephron loop and collecting duct

The volume of blood at the end of vasa recta is ___ than the beginning

greater

What structure preserves the osmotic gradient?

Vasa recta through the countercurrent exchanger

Permeability of the vasa recta

The entire length of the vasa recta is highly permeable to water and solutes

Because the vasa recta is permeable to both water and solutes what can we say about it and the vasa recta?

the vasa recta and its surrounding interstitial fluid, the blood within the vasa recta remains nearly isosmotic to the surrounding fluid

- does NOT undo the osmotic gradient

At the beginning of the vasa recta descending limb osmolarity = 300mOsm but at the end of the ascending limb osmolarity = 325mOsm why?

because oxygen and nutrients are brought in while metabolic waste is removed

Why is blood flow to the inner medulla so low? (0.3%)

The inner medulla houses the tip of the loop of Henle where urine is the most concentrated. We have little blood flow here to prevent 'wash out' of this region.

Collecting duct role

it tunes how much fluid we absorb/excrete to maintain the Posm at 300.

Urea role

helps form medullary gradient (concentrate urine)

Pathway of urea in the nephron loop

Enters filtrate in ascending thin limb of nephron loop by facilitated diffusion

Cortical collecting duct reabsorbs water; leaves urea

In deep medullary region now highly concentrated urea → interstitial fluid of medulla → back to ascending thin limb → high osmolality in medulla

Source of urea for the body

dietary protein

recycled protein

Where is urea located in relation to the nephron loop?

At the tip of the loop of Henle (to facilitate urine concentration)

If we eat a lot of protein, we excrete ____ urea than if we didn't

more

The collecting duct is naturally ___. Which hormone is responsible for water and urea uptake in the collecting duct?

- constricted

- ADH

Three players of the osmotic gradient

- long nephron loops (countercurrent multiplier)

- vasa recta (countercurrent exchanger)

- collecting ducts (adjust urine osmolality)

What is the maximum osmolality the nephron loop can reach?

1200mOsm

What hormone is secreted when osmolarity of blood rises?

ADH is secreted to bring it back to normal levels

Another name for ADH

Vasopressin

Effect of vasopressin - Step 1

Blood-borne vasopressin binds with its receptor sites on the basolateral membrane of a distal or collecting tubule cell

Effect of vasopressin - Step 2

This binding activated the cyclic AMP second-messenger system within the cell

Effect of vasopressin - Step 3

Cyclic-AMP increases the opposite luminal membrane's permeability to H2O by promoting the insertion of water channels in this membrane. This membrane is impermeable to water in the absence of vasopressin.

Effect of vasopressin - Step 4

Water enters the tubular lumen through the inserted water channels and subsequently enters the blood, in this way being reabsorbed. Water exits the cell through a different water channel permanently positioned at the basolateral border.

Aquaporins

(AQP) channels that allow entry of water

Different types: AQP-3, AQP-4

Body's response to dehydration

- ADH is released to reabsorb more water

- decreased water excretion

- Thirst

What structure does ADH act on? and how?

collecting ducts increases number of water channels in principal cells

When we aren't dehydrated does ADH secretion completely stop?

No, it does decrease but we have a constant low level of ADH

Why do we have basal secretion of ADH?

To keep Posm at 300

ADH depends on what in order to be secreted?

medullary gradient and presence of urea

Consequence for severely malnourished individuals concerning ADH secretion

lack of food = lack of urea

ADH cannot be secreted

Body's response to water intake

ADH secretion is decreased because we don't need to reabsorb more water in this situation

Under what conditions would we produce dilute urine?

overhydration

Making diluted urine

Filtrate at top of ascending limb is dilute due to salt removal

in the absence of ADH the collecting ducts remain impermeable to water & very dilute urine produced

When urine is diluted does the tip of the loop of Henle become concentrated?

No, the mOsm of the tip of henle is less than that of concentrated urine

What does it mean when the tip of the loop of Henle reaches 1200mOsm?

- urine is very concetrated

- dehydration

- NO URINE will be excreted

What are the two triggers of ADH secretion?

decreased plasma volume and increased plasma osmolality

As blood volume decreases, what happens to ADH secretion?

ADH secretion increases

What % of blood volume loss triggers ADH secretion?

10%

What regulates the sodium concentration of the ECF?

ADH and thirst mechanisms

What regulates sodium concentration of the body?

ANP hormone

Renin-angiotensin-aldosterone system

ANP hormone

atrial natriuretic peptide

ANP function

ANP hormone Increases water and sodium excretion