UCD

Maintain stable plasma osmolarity

What is the kidney's role in relation to plasma osmolarity?

Adjusting free water excretion

How does the kidney respond to changes in water and solute intake or loss?

Formation of concentrated urine (more concentrated than plasma)

What does increased plasma osmolarity lead to in terms of urine concentration?

Diluted plasma osmolarity

What leads to the excretion of dilute urine?

Antidiuretic hormone (ADH)

What is the critical hormone determining whether the kidney produces concentrated or dilute urine?

Simple linear relationship

What is the relationship between the concentration of ADH in the blood and plasma osmolarity?

Around 285 to 288 mOsm/L

What is the normal set point for plasma osmolarity?

Low resting ADH concentration

What ADH concentration is associated with the normal plasma osmolarity set point?

To defend against dehydration

What is the ADH system calibrated to defend against?

A large potential to increase

What potential does increasing plasma osmolarity have on ADH levels?

Doesn't allow for a large decrease from its resting point to almost no ADH

What limitation exists regarding ADH levels during overhydration?

About a 1% deviation

How small of a change in osmolarity can alter the rate of ADH secretion?

Body's volume status

What else does the sensitivity of the ADH secretion mechanism depend on besides osmolarity?

Steeper (more sensitive)

How does low volume status affect the ADH secretion curve?

Less sensitive

How does high volume status affect the ADH secretion curve?

A small peptide produced by the posterior pituitary

What is the chemical nature and source of ADH?

The hypothalamus

What part of the brain controls ADH production?

Supraoptic and paraventricular nuclei

What specific nuclei in the hypothalamus contain cell bodies that make ADH?

Posterior pituitary

Where is ADH stored before release into the bloodstream?

Neurosecretion

What process leads to ADH release into the bloodstream?

Osmoreceptors and baroreceptors

What are the two main types of receptors involved in the control of ADH release?

Hypothalamus

Where are osmoreceptors located?

Changes in neuron volume

What do osmoreceptors respond to?

Patient's volume status

What information do baroreceptors provide?

Osmoreception

Normally, what is the system most sensitive to in controlling ADH release?

About 10%

By how much must extracellular volume decrease for baroreceptors to become a very strong independent driver of ADH secretion?

Increased plasma osmolarity or independently by a low volume state

What are the two main drivers of ADH secretion?

Decrease water excretion

What is the effect of increased ADH on renal water excretion?

Lower plasma osmolarity and increases total body water

How does decreased water excretion help in regulating plasma osmolarity and body water?

Along the nephron and collecting duct

Where can the effect of ADH be observed in the kidney?

Proximal tubule, descending and ascending loops of Henle, distal convoluted tubule, and cortical and medullary collecting ducts

What are the segments of the nephron along which tubular urine travels?

Basically no change in osmolarity regardless of ADH levels

What happens to the osmolarity in the proximal tubule with varying ADH levels?

Does not directly contribute to varying urine concentration

Why doesn't the proximal tubule play a direct role in varying urine concentration based on ADH?

Increases

What happens to the osmolarity of the fluid in the descending thin limb of Henle's loop?

Much greater in the presence of high ADH compared to low ADH

How does the presence of high ADH affect the increase in osmolarity in the descending thin limb?

Very water permeable, so the osmolarity inside reflects the osmolarity of the medullary interstitium

What permeability characteristic defines the descending thin limb, and what does its fluid osmolarity reflect?

Greatly increases medullary interstitial osmolarity

What effect does high ADH have on medullary interstitial osmolarity, contributing to the descending thin limb's function?

Decreases, becoming quite dilute (hypotonic) compared to plasma

What happens to the osmolarity of the fluid as it ascends the ascending limb of Henle's loop?

The diluting segment

What is the ascending limb of Henle's loop known as?

Very low water permeability

When ADH levels are low, what is the water permeability of the collecting duct system?

Remains dilute

When ADH is low, what happens to the hypotonic fluid entering the distal nephron as it passes through the collecting duct?

Very high water permeability

When ADH levels are high, what is the water permeability of the collecting system?

Osmotic water reabsorption back into the hypertonic medulla

What occurs in the collecting duct when ADH levels are high?

Retains water in the body and concentrates the urine

What are the consequences of osmotic water reabsorption in the collecting duct?

Increasing water permeability in the collecting duct

What is a major effect of ADH on the collecting duct?

How ADH leads to high medullary osmolarity and how it varies the water permeability of the collecting duct

What are the next steps in understanding urine concentration and dilution related to ADH?

The tubules

What does the existence of a hypertonic medulla depend on?

Countercurrent multiplication system

What is the system involving tubules that creates a hypertonic medulla called?

Vascular mechanism

Maintaining the hypertonic medulla involves what type of mechanism?

Countercurrent exchange

What is the vascular mechanism that maintains the hypertonic medulla called?

The loop of Henle and the collecting duct

What are the main tubular structures involved in the countercurrent multiplier?

Opposite directions

In the loop of Henle, in what direction does tubular urine flow in the descending and ascending limbs?

Ability to create a difference in osmolarity of about 200 mOsm at any horizontal level of the loop of Henle

What is the single osmotic effect?

The process where the single osmotic effect is multiplied due to the countercurrent flow, leading to the piling up of solute at the tip of the tube and a four-fold difference in osmolarity between the cortex and medulla

What is countercurrent multiplication?

By dumping solute from inside the tubule into the medullary interstitium, making it more concentrated

How does countercurrent multiplication work to concentrate the medulla?

Thick ascending limb

Which part of the nephron actively reabsorbs sodium chloride and deposits it into the interstitium in countercurrent multiplication?

Sodium-potassium-2 chloride cotransport system

What specific transporter is involved in sodium chloride reabsorption in the thick ascending limb for countercurrent multiplication?

Stimulates this sodium chloride transport in the thick ascending limb

What effect does ADH have on the sodium chloride transport in the thick ascending limb?

Urea

Besides sodium chloride, what is another very important solute in the medullary interstitium?

About 40%

Approximately what percentage of the total solute content in the medullary interstitium does urea make up?

Diffuses out of the medullary collecting duct via uniporters

What happens to urea in the presence of high ADH?

Increases the urea concentration in the medullary interstitium

What is the consequence of urea movement out of the collecting duct?

An effective osmolyte, drawing water out of the water-permeable descending thin limb by osmosis

How does urea in the medullary interstitium contribute to urine concentration?

Sodium chloride and water

What are the main components of the fluid entering the descending thin limb from the proximal tubule?

Becomes more concentrated with sodium chloride

What happens to the fluid inside the descending thin limb as water is drawn out?

A simple diffusion gradient for sodium chloride out of the tubule and into the interstitium

What drives sodium chloride movement out of the ascending thin limb?

Highly sodium chloride permeable but very water impermeable

What are the permeability characteristics of the ascending thin limb?

Further increasing the interstitial osmolarity while water is retained in the lumen

What is the effect of sodium chloride moving out of the ascending thin limb on the interstitial osmolarity and water in the lumen?

Further reduces the sodium chloride concentration in the lumen through active transport

What does the thick ascending limb do to the sodium chloride concentration in the lumen after the ascending thin limb?

Dilute fluid entering the distal nephron

What is the characteristic of the fluid entering the distal nephron after passing through the loop of Henle?

Strongly stimulates both sodium chloride transport in the thick ascending limb and urea transport out of the medullary collecting duct

What effects does ADH have on the thick ascending limb and medullary collecting duct that drive countercurrent multiplication?

Unique anatomy of its microcirculation, specifically the vasa recta

What allows the kidney to maintain a high medullary interstitial osmolarity?

Capillary loops that run parallel with the loops of Henle

What are the vasa recta?

Traps solutes in the medullary interstitium through a process of diffusion

What is the function of the loop arrangement of the vasa recta?

Solutes enter the blood and water leaves by diffusion

What happens to solutes and water as blood flows down the descending vasa recta into the hypertonic medulla?

Solutes diffuse out and water moves in by osmosis

What happens to solutes and water as the now concentrated blood flows up the ascending vasa recta?

Cycling solutes within the medulla

What is the net effect of the countercurrent exchange mechanism in the vasa recta?

More efficient with low medullary blood flow

Under what condition is the countercurrent exchange mechanism more efficient?

Decrease medullary blood flow

What effect do high ADH states have on medullary blood flow?

Wash out the medullary interstitial gradient

What tends to happen to the medullary interstitial gradient in low ADH states due to increased blood flow?

Water reabsorption in the collecting duct

What determines whether the final urine is dilute or concentrated?

ADH

What hormone controls the change from a water-impermeable to a water-permeable epithelium in the collecting duct?

Insertion of aquaporin 2 water channels into the luminal cell membranes of principal cells

What is the mechanism by which ADH increases water permeability in the collecting duct?

Medullary interstitium is very hypertonic

What is the condition of the medullary interstitium when ADH levels are high?

Water moves out of the collecting duct lumen via aquaporin 2

How does water move in the collecting duct when ADH is high?

Concentrate the urine

What is the result of water moving out of the collecting duct lumen when ADH is high?

V2 receptors at the basolateral membrane

Where does ADH bind in the principal cells of the collecting duct?

Cyclic AMP response

What intracellular signaling pathway is triggered by ADH binding to V2 receptors?

Insertion of aquaporin 2 channels in the luminal membrane

What is the downstream effect of the cyclic AMP response in principal cells?

Present at the basolateral membrane all the time

Where is aquaporin 3 located in the principal cells?

At the luminal side with the presence or absence of aquaporin 2

Where does the crucial regulatory step of water permeability occur?

Hypotonic fluid entering the collecting duct remains in the lumen

What happens to the fluid entering the collecting duct when ADH levels are low?

Dilute final urine

What is the result of low water permeability in the collecting duct when ADH is low?

Aquaporin 2 channels are internalized into vesicles within the cell

Why is the luminal membrane impermeable to water when ADH is low?

Facultative reabsorption

What is water reabsorption under ADH control known as?

About 20+ liters per day

Approximately how much water can be reabsorbed daily through facultative reabsorption?

Obligatory water reabsorption

What is water reabsorption in more proximal nephron segments called?

Is not under ADH control

Is obligatory water reabsorption regulated by ADH?

Diabetes insipidus (DI)

What condition results from a completely dysfunctional ADH system?

As much as 20 to 25 liters of water per day

How much water could a person with diabetes insipidus excrete daily?