Physio II: Regulation of Extracellular Fluid

Why is the regulation of water and electrolyte levels important?

It is is critical for maintaining homeostasis.
Many bodily systems will not properly if water or electrolyte levels increase or decrease beyond their normal limits.
Fluid balance is implicitly linked to electrolyte balance. Electrolytes establish osmotic

How is body water regulated?

1. fluid intake, which is controlled by factors that affect thirst.
2. excretion of water by the kidneys.

What would be the effect of urine when the kidneys can excrete a dilute urine?

The urine would be hypo-osmotic to plasma.

When would it be advantageous for the kidney to excrete a dilute urine?

Ingestion of large quantities of water

What would be the effect of urine when the kidneys can excrete a concentrated urine?

The urine would be hyper-osmotic to plasma.

When would it be advantageous for the kidney to excrete a concentrated urine?

Dehydration

What substances are controlled?

ECF sodium concentration and osmolarity are controlled.
Fluid and salt intake are controlled.

What is required for the kidney to be able to excrete urine of varying osmolarity?

Solute to be separated from the water at some point in the nephron.

What is required for excretion of dilute or concentrated urine?

Normal function of the loop of Henle.

What does ADH do?

Increases permeability of distal tubule and collecting ducts and medullary ducts to water so urine volume decreases (increases the reabsorption of water)

Does ADH alter the rate in which solutes are excreted?

ADH does not alter the rate in which solutes are excreted.

What is the effect of high ADH?

What is the effect of low ADH?

What is the effect of alcohol on ADH?

It inhibits it.

Dilute urine would be _______.

Hypo-osmotic
Therefore, Concentrated urine would be hyper-osmotic.

Excess water is eliminated by the kidneys by formation of urine that is _______ to plasma.

Hypo-osmotic

Nephron must reabsorb solute from _______ fluid and not allow water to _______.

Nephron must reabsorb solute from TUBULAR fluid and not allow water to FOLLOW.

What happens to levels of ADH when forming dilute urine?

ADH is LOW

What happens in the proximal tubule in regards to NaCl and water?

In the proximal tubule, active NaCl transport is followed by the passive movement of water.
Therefore, fluid entering the descending limb of the Loop of Henle from the proximal tubule will be iso-osmotic with respect to plasma.

Describe the permiablility of water, NaCl, and urea in the descending limb of the Loop of Henle?

It is highly permeable to water but not very permeable to NaCl or urea.

What happens to water in the tubular fluid as it move down the medulla?

Water leaves the tubule by osmosis due to an osmotic gradient in the ISF.

What would be the osmolarity of the tubular fluid at the bend of the loop?

The osmolarity of the ISF (higher than 300 mOsm/L)

What are the relative composition of the tubular fluid and the interstitial fluid in the descending limb of the Loop of Henle?

i. [NaCl] greater than ISF
ii. [urea] less than than ISF

Describe the permiablility of water, NaCl, and urea in the ascending limb of the Loop of Henle?

It is impermeable to water (under all conditions) but
permeable to NaCl and urea.

What happens as tubular fluid moves up the thin ascending limb?

NaCl is passively reabsorbed (NaCl in tubule > ISF, so NaCl levels decrease in tubule
Urea passively moves into the tubular fluid because urea levels in the ISF > tubular fluid
Volume stays the same

Will the tubular fluid become diluted or concentrated?

NaCl movement out > urea movement in so becomes diluted.

Describe the permiablility of water and urea in the thick ascending limb of the Loop of Henle?

It is impermeable to water (under all conditions) and urea.

What happens to NaCl in the thick ascending limb of the Loop of Henle?

NaCl levels in tubular fluid decrease because active reabsorption using the Na?/2Cl?/K? cotransporter

Describe the fluid leaving the thick ascending limb of the Loop of Henle in relation to plasma?

Fluid leaving this segment is hypo-osmotic with respect to the plasma.

What happens in the late distal tubule and cortical portion of the collecting duct?

Actively reabsorb NaCl but are impermeable to urea.
In the absence of ADH, these segments are impermeable to water.

What happens to tubular fluid in the late distal tubule and cortical portion of the collecting duct?

Because NaCl is reabsorbed without water, tubular fluid is diluted more.

Describe the fluid leaving the late distal tubule and cortical portion of the collecting duct in relation to plasma?

Fluid leaving the collecting duct will be hypo-osmotic with respect to the plasma.

What happens to the concentration of urea?

It increases

What happens in the medullary collecting duct?

The medullary collecting duct actively reabsorbs NaCl. Even in the absence of ADH, this segment is slightly permeable to water and urea. (In the presence of ADH, its water and urea permeability increases.) Consequently, some urea enters the collecting duc

Therefore, as the kidney excretes excess water, what happens to the Urine osmolality as well as the NaCl and Urea concentrations?

Urine osmolality will be low
NaCl and urea concentration will be low

Water is conserved by the formation of urine that is __________ to plasma.

Hyper-osomotic

What is required for the kidney to conserve water?

Requires the removal of water from the tubular fluid, while leaving solute behind.

What is Obligatory urine volume?

Minimum volume of urine required to excrete the solutes formed in the body.

How much urine must be excreted each day?

In a 70-kg man, about 600 mOsm of solute must be excreted each day.

If the maximum urine osmolarity is 1200 mOsm/L, then what must be the volume of urine that must be excreted?

0.5 L.
600 mOsm/day � 1200 mOsm/L = 0.5 L/day

Do you think the obligatory urine volume of a beaver is higher or lower than a human?

HIGHER (500 mosm/L is the highest concentration of urine they can achieve)
They don't have to concentrate their urine as much since they are adapted to water environments.

Do you think the obligatory urine volume of the Australian hopping mouse (a desert dweller) is higher or lower than a human?

LOWER (10,000 mOsm/L is the highest concentration of urine they can achieve)

What are the requirements for excreting concentrated urine (Anti-diuresis)?

1. ADH
2. hyperosmotic renal medulla
3. countercurrent multiplier (thick ascending limb of Loop of Henle) - Within the medullary pyramids; creates the gradient
4. countercurrent mechanism (vasa recta) - maintains the gradient
5. juxtamedullary nephrons (l

What is hyperosmotic renal medulla?

Water can only move passively (driven by osmotic gradient); the kidneys must create a hyper- osomotic environment gradient that drives the removal of water from the tubular flui. The gradient is created in the medullary ISF.

What are the steps in the formation of concentrated urine (Questions 45 to 51)?

Steps 1-4 are similar to formation of dilute urine.
The NaCl that is reabsorbed by the ascending limb of the Loop of Henle is accumulating into the interstitium of the medulla. This raises the osmolarity.
This will provide the osmotic driving force for wa

Why is the fluid reaching the collecting duct is hypo-osmotic with respect to the plasma?

NaCl reabsorption from the thick ascending limb

In the presence of ADH, the collecting duct is permeable to water. So as the fluid continues moving down the duct towards the medulla, what happens?

Water diffuses out of the lumen
Urine osmolarity increases
Urine osmolarity in the cortical collecting duct will maximally be 300 mOsm/L (Osmolarity in the surrounding ISF)

How does the fluid composition change entering the descending limb?

[NaCl] less than fluid that entered the descending limb
Solutes that account for the osmolality creatinine, urea, etc

The outer medullary duct is permeable to water in the presence of ADH, so as the fluid moves through the outer medulla, what happens?

Water diffuses out of the tubule
Urine osmolarity steadily increases
Note: The outer medullary duct is impermeable to urea, so [urea] increases

What happens in the permeability of the inner medullary duct to urea in the presences of ADH?

The permeability of the inner medullary duct to urea and water is increased in the presence of ADH.
The [urea] in the tubular fluid is greater than the surrounding interstitium due to the water reabsorption in the cortex and medulla. Consequently, some ur

What happens to urine in the presence of ADH?

Urine osmolarity 1200-1400 mOsm/L (the osmolarity of the ISF)
[urea] high (600 mOSm/L - that of surrounding ISF)
Urine volume low (0.5 L/day)

What is urea?

Metabolic by-product of protein metabolism

Urea contributes about __________ of the osmolarity in the medullary interstitium

40-50%

The permeability of most of the tubule involved in urinary dilution or concentration (loop, DT, CD) is low, with the exception of the medullary duct (especially in the presence of ADH). Therefore, what happens to the [urea] as it moves thru the tubule?

Increase

As the fluid reaches the inner medullary duct [urea] is _________?

High

ADH increases the permeability of the duct to urea, so what happens to urea?

Passively diffuse out into the ISF

What is the role of urea transporters?

facilitates transport (increased by ADH)

What happens to urea in the loop of Henle?

Some of the urea diffuses into both limbs of the loop of Henle. The urea is trapped in the tubule until it reaches the medullary duct again. Therefore, urea recycles from the interstitium to the nephron and back into the interstitium. This helps to accumu

What happens when there is excess water in the body?

Urine flow rate higher
Concentration of urea in the inner medullary ducts lower
Diffusion of urea into the medullary interstitium less
ADH levels low
Permeability of ducts to water and urea low

What is the role of Vasa Recta?

A special system for supplying blood flow to the renal medulla is needed so nutrients and oxygen can get
to the tissues, but will not dissipate the osmotic gradient created by countercurrent multiplication.

Is the blood flow in the medulla high or low?

Low

Explain the mechanism of the Vasa Recta in Maintaining the Osmotic Gradient in the Medulla?

The countercurrent exchange mechanism helps to maintain the gradient
a. The vasa recta are permeable to solutes in the blood (except plasma proteins).
b. Solutes diffuse into the vasa recta and water moves out into the interstitium as blood moves toward t

Why does the kangaroo rat have loops of Henle that reach down to the tips of the papillae, while beavers have a relatively short loop of Henle?

Longer the loop, th elonger the vertical osmotic gradient

What is urine specific gravity?

Urine specific gravity is a measure of weight of solutes in a given volume of urine, so it is determined by the number and size of the solute molecules. It is often used clinically to give a quick estimation of urine solute concentration.

What is the relationship between urine specific gravity and the concentration of urine?

The higher the specific gravity, the more it is concentrated

If a person was dehydrated, would they have a high or low urine specific gravity?

High

Why is the Osmolarity of the ECF and the regulation of Na? closely linked?

Because Na? is the major ion in the ECF.

What are the Na? osmolarity ranges?

140 - 145 mEq/L.

Why must Na? and osmolarity be strictly controlled?

Determines the distribution of fluid between ICF and ECF compartments

Plasma osmolarity can be estimated by what plasma ion and what is the equation?

Plasma Na?
Posm = 2.1 x plasma sodium concentration

What happens to plasma osmolarity with a water deficit or excess?

Water deficit ? plasma osmolarity
Water excess ? plasma osmolarity

Osmoreceptors in anterior hypothalamus will do what if plasma osmolarity increases or decreases?

The change in volume of the osmoreceptor cells will cause them to change their firing rate, which affects firing of the impulses to the posterior pituitary.
Shrinkage causes them to fire at a greater rate

What will a change in the number of action potentials transmitted to the posterior pituitary affect?

It will affect the release of ADH stored in nerve endings.

Review what will occur with a water deficit.

Review what will occur with a water excess.

Where is ADH synthesized and stored?

ADH is made in the supraoptic and paraventricular nuclei (SON and PVN) of the hypothalamus. (most is made in the SON)
ADH is transported down the axons of these nuclei to the neurohypophysis where ADH is stored.
Osmoreceptors in the hypothalamus are neuro

What receptors cause a release of ADH?

Afferent stimuli from baroreceptors and receptors in the atria are carried up through CN IX and X with synapses in the nucleus tractus solitarius. Projections to the SON and PVN will affect ADH release.

Review ADH regulation.