Water balance, Concentration, and Control of ECF

What two things contribute to the osmotic gradient in the kidney?

NaCl and urea

What two structural components help cause the medullary hyperosmolarity?

Length of loop on Henle and medullary thickness

What transporter is responsible for creating hyperosmolarity in the medulla?

The NKCC in the thick ascending limb

How is hyperosmolarity maintained in the medulla?

Different NaCl and H2O permeabilities in the loop of Henle

What is secreted in the thin ascending limb?

Urea

To what osmolarity can NKCC produce?

It makes the interstitiam 200mOsm/L more than inside the tubular fluid

What vascular structure is responsible for preserving tubular hypertonicity?

The vasa recta

What is the vasa recta permeable to?

NaCl and H2O

What is the force that created the gradient called?

Countercurrent multiplication

What is the force that keeps the gradient intact called?

Countercurrent exchange

What are the two halves of what concentrates urine?

½ NaCl ½ Urea

What does urea remove from the body?

Ammonia

As water is removed from the thin descending limb what happens to urea concentration?

It goes up

Is the thin descending limb permeable to urea?

No

What are the two urea permeant regions of the nephron?

The thin ascending limb and the intermedullary collecting duct

How does urea increase NaCl reabsorption?

It increases osmolarity in the thick ascending limb and distal tubule to make it easier for NaCl reabsorption

How is urea recycled?

It travels through the TALH and the DT until it leaves the intermedullary collecting duct. It then is put back into the thin ascending limb after leaving the intermedullary collecting duct.

What does ADH do to urea levels?

It increases the amount that is recycled by increasing permeability in the intermedullary collecting duct

How does ADH maximize hypertonicity?

It increases water leaving the collecting duct and urea uptake into the itnerstitium to double increase hypertonicity.

Is most of the urea permeability in the medulla or the cortex?

The medulla

How is ADH released?

1. Osmoreceptors in circumventricular organs sense change

2. Hypothalamus receives signal from osmoreceptors

3. Posterior pituitary receives signal from hypothalamus

   1. Posterior pituitary releases ADH

ADH release impairment is a symptom of what disease?

Diabetes insipidus

Does a decrease in blood volume cause a release in ADH?

Yes, but it takes a large change in volume to make a change while only a small change in osmolarity is required

What are the three effects of ADH release?

1. Thirst

2. Mild pressor effects

3. Increase in aquaporins (most important)

Why are ADH effects quicker that steroid hormone effects?

They do not require transcription

What is the process of ADH increasing the amount of aquaporins in the membrane?

ADH binds extracellularly

cAMP levels rise

Vesicles with pre-synthesized aquaporins fuse to the membrane

During water diuresis is the urine dilute or concentrated?

dilute (there is no ADH)

During antidiuresis is the urine dilute or concentrated?

Concentrated (maximum ADH)

Why does having more principal cells in the medullary region cause a greater concentration of urine?

There are more cells that are responsive to ADH

What is the difference between central diabetes insipidus and nephrogenic diabetes insipidus?

In central the problem is ADH release and in nephrogenic the problem is at the receptor in the nephron

How do you test for diabetes insipidus?

You deprive water. If the subject has DI then ADH will be released and the urine will be more conentrated

How do you test between central and nephrogenic diabetes insipidus patients?

You administer ADH. If water reabsorption is increased then the patient either does not have DI or they have central DI.

If water reabsorption does not occur, then they have nephrogenic DI.

Why is the extracellular concentration of sodium not a good indicator of ECF volume?

Because it is very variable. It you eat pretzels it will go up, if you drink water it will go down

What determines how much sodium is excreted?

The total amount of sodium, not the concentration

What big enzyme system stimulates the release of aldosterone?

RAS

What is a drug that inhibites ENaC

Amiluride

What effect does aldosterone have on Na+

It causes more transcription of ENaC so more absorption

AND it increases the probability an ENaC channel is open

What external stimuli will cause the release of aldosterone?

Stress

If sodium levels are two high what peptide can bring them down?

Atrial Natriuretic Peptid

What is the pathway of Atrial Natriuretic Peptide bringing down ENaC activity?

It stimulates guanylyl cyclase to produce cGMP

cGMP brings down activity of ENaC