6 - Urine Concentration and Dilution Flashcards

1
Q

What is the normal response of a human to ingestion of 1 liter of water? What was the urine flow rate prior to consumption?

A

Prior to consumption: UR = 0.1 ml/min of hypertonic urine (600mOscm/L)

After ingestion: initially, small decrease in plasma osmolarity.

Minutes later: marked increase in urine flow rate, and urine osmolarity drops significantly and becomes hypotonic (<200 mOsm/L).

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2
Q

What does not change during the process of reestablishing plasma osmolarity after ingestion of 1L water?

A

Urinary solute excretion rate was barely changed.

This is because the kidney has the ability to separate solute from water through altering the solute concentration (osmolarity) of urine.

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3
Q

How much of the filtered load of water is reabsorbed in the PT? What type of reabsorption is this?

A

~2/3.

This is isosmotic reabsorption

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4
Q

What is the osmolarity in the interstitial space in the renal cortex?

A

300 mOsm/L.

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5
Q

What occurs under conditions when concentrated urine is being formed in terms of osmolarity?

A

A gradient is formed from the border of the cortex and medulla (300 mOsm/L) with a progressive increase in osmolarity in the deeper (further from cortex) portions of the medulla to about ~1200 mOsm/L

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6
Q

What happens when fluid descends the thin descending limb?

A

The fluid is isotonic to the plasma enters a water permeable segment where the interstitial space has a greater and greater osmolarity.

Water therefore leaves, and the tubular fluid reaches an osmotic equilibrium with the interstitial space at each level.

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7
Q

What happens when fluid makes the turn into the thin ascending loop of henle?

A

Sodium passively diffuses out and the tubular fluid in the lumen begins to equilibrate with that in the interstitium.

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8
Q

What happens when the fluid reaches the thick ascending loop of henla?

A

Impermeable to water but has an active Na/K/2Cl transporter.

This segment generates an osmotic gradient of about 200 mOsm/L between the lumen and interstitial space.

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9
Q

Where is the thick ascending limb located? What does the luminal osmolarity be reduced to in this segment?

A

Starts in the outer medulla but transitions into the cortex.

Since it can generate a 200mOsm/L gradient in the cortex where the interstitial, then the luminal osmolarity can be reduced to approximately 100 mOsm/L.

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10
Q

What happens to the tubular fluid in the early distal tubule?

A

It’s impermeable to water, and demonstrates active Na reabsorption by the thiazide-sensitive Na/Cl so-transporter.

Further dilution of tubular fluid can occur here.

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11
Q

What happens to tubular fluid in the late distal tubular and collecting duct?

A

In the presence of ADH, which increases water permeability, water follows the osmotic gradient and reaches osmotic equilibrium at each level of the medulla.

By the end, the fluid (urine) is hypertonic with an osmolarity of 1200 mOsm/L.

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12
Q

What does the process of urine concentration achieve?

A

It turns a large volume of isotonic fluid into a small volume of concentrated fluid.

Enables body to excrete solute while retaining water.

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13
Q

What is countercurrent multiplication? What does it depend on?

A

A method used by the kidney to establish the medullary concentration gradient. Depends on two closely associated segments with differing permeability.

Removal of water in the descending limb and NaCl in the ascending limb to achieve equilibrium causes an accumulation of Na in the medulla.

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14
Q

What else does the medulla have a high concentration of?

A

Urea.

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15
Q

What is the interstitial osmotic gradient composed of?

A

Approximately equal amounts of urea and NaCl.

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16
Q

What happens to urea in the PT?

A

It is passively reabsorbed.

In the distal portions of the PT, urea concentration is equal to that of plasma.

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17
Q

How does the concentration of urea change in the thin descending and ascending limb?

A

In descending limb, water reabsorption causes increased urea concentration.

Carrier-mediated diffusion aids in the secretion of urea in the ascending limb.

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18
Q

What happens to urea in the thick ascending limb to the medullary collecting duct? What about the late distal tubule and collecting duct?

A

Thick ascending and medullary CD impermeable to urea.

In the late distal tubule and collecting ducts urea concentration is elevated because water is reabsorbed.

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19
Q

What occurs with urea in the distal portion of the inner medullary collecting duct?

A

When ADH is present, urea permeability is high.

Urea is reabsorbed in this segment, leading to movement of urea into the medullary interstitial space.

(this is impermeable to urea when ADH is absent)

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20
Q

How do the vasa recta capillaries play a role in formation and concentration or dilution of urine?

A

They provide nutritive blood flow to renal tubular structures and serve and help return reabsorbed water and solute to the plasma.

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21
Q

What would happen if the vasa recta capillary bed was arranged in a standard fashion? Why doesn’t this happen?

A

Their reabsorptive process would lead to a dissipation of the renal medullary osmotic gradient.

Instead their arranged in loops to permit countercurrent exchange of fluid between the descending and ascending vessels.

22
Q

What are the vasa recta permeable to? What does the countercurrent exchange in the vasa recta prevent?

A

Sodium, urea, and water.

Prevents loss of medullary solutes.

23
Q

The formation of concentrated or dilute urine is a function of what?

A

The presence or absense of ADH.

High ADH - maximal concentrating

Low ADH - diluting conditions

24
Q

Where does ADH have its effects?

A

It influences water reabsorption in the late distal tubule and the collecting duct.

It also influences urea reabsorption in the inner medullary CD.

25
Q

How does reabsorption in the PT change with ADH present?

A

It does not change.

26
Q

How does reabsorption in the loop of henle change with high and low ADH?

A

Reabsorption differs in the presence of ADH because of the altered medullary interstitial osmotic gradient.

Permeability of the descending limb is unaltered.

27
Q

What occurs in the ascending loop and early distal tubule in the presence of high or low ADH?

A

Reabsorption of NaCl dilutes the tubular fluid to hypotonicity.

28
Q

What effect does ADH have on the distal tubule and collecting duct?

A

ADH present: water is reabsorbed and urine is concentration.

ADH absent: large volume of dilute urine is excreted.

29
Q

Urine concentration problems are often associated with what?

A

Problems of ADH secretion or action, loss of medullary gradient due to changes in blood flow, or when sodium transport in the thick ascending loop is inhibited.

30
Q

What happens when ADH is low?

A

The collecting duct is impermeable to urea.

Medullary urea gradient is lost.

Urine is dilute because tubular fluid was made dilute in thick ascending limb and without ADH no water is reabsorbed along with sodium in the distal nephron.

31
Q

What effect does ADH have on the osmolarity in the tubular fluid?

A

It increases the osmolarity to about 1200 mOsm/L in the medullary collecting duct and allows the excretion of concentrated urine.

32
Q

What type of molecule is ADH and where it it made?

A

Peptide found in the cells of the supraoptic (SO) and paraventricular (PVN) in the hypothalamus.

These cells have projections to the posterior lobe of the pituitary where ADH is secreted into the blood.

33
Q

What are the two main stimuli for the release of ADH? What detects this stimuli?

A

Changes in extracellular osmolarity and changes in extracellular volume.

34
Q

How does the body detect changes in extracellular volume?

A

Osmoreceptors in the anterior hypothalamus near AV3V.

There’s no BBB in this region so changes in blood composition are reflected in the interstitial fluid in the brain.

35
Q

What happens near osomoreceptors when the extracellular osmolarity is increased?

A

The cells will shrink as water leaves the osmoreceptor cells.

Then a signal is sent to the SO and PVN to release ADH.

36
Q

What happens with osmoreceptors when the extracellular osmolatiry decreases?

A

The osmoreceptors swell and release of ADH is inhibited.

37
Q

How does the body detect changes in extracellular volume?

A

Through baroreceptors in the thoracic veins, atria, carotid artery, and aorta.

38
Q

What happens when ECF volume is decreased?

A

A decrease in pressure in the baroreceptors in the thoracic veins and atria, carotid and aortic baroreceptors is sensed.

Signal integrated into the nucleus tractus solitarius, and projections to the SO and PVN lead to an increase in ADH release.

39
Q

What are some factors that decrease ADH secretion? What drugs decrease ADH?

A

Low plasma osmolarity, high blood volume, high blood pressure.

Drugs: alcohol, clonidine, haloperidol.

40
Q

What are some factors that increase ADH?

A

Increased plasma osmolarity, decreased blood volume, decreased blood pressure, nausea, and hypoxia.

Drugs: Morphine, nicotine, and cyclophosphamide.

41
Q

Besides ADH, what else regulates urine output?

A

The sensation of thirst, controlled by osmoreceptors in the AV3V and by input from baroreceptors/cardiopulm receptors via projections in the NTS.

42
Q

Where is the thirst center located?

A

Anteriolaterally in the preoptic nucleus in the hypothalamus.

43
Q

What are factors that increase thirst?

A

Increased plasma osmolarity, decreased blood volume, decreased blood pressure, increased angiotensin II, and dry mouth.

44
Q

What are factors that decrease thirst?

A

Decreased plasma osmolarity, increased blood volume, increased blood pressure, decreased angiotensin II, and gastric distension.

45
Q

What is hypernatremia? What can occur?

A

PNa > 150 mEq/L

  1. loss of extracellular water due to diabetes insipidus or dehydration
  2. Sodium retention and/or excess sodium intake due to excess secretion of aldosterone (causes Na retention)
46
Q

How does plasma sodium change when there is an intact thirst/ADH system? What about when it’s not in tact?

A

About 1-2 mEq/L over a 5-fold range.

When broken, there’s a direct relationship between sodium intake and plasma sodium levels.

47
Q

What is hyponatremia and what can occur?

A

PNa <135 mEq/L

  1. Excess retention and/or intake of water caused by excess ADH secretion
  2. Increased excretion and/or decreased sodium intake due to diarrhea, vomiting, or overuse of diuretics.
48
Q

What is central diabetes insipidus?

A

Failure to produce ADH.

49
Q

What is nephrogenic diabetes insipidus?

A

Failure of kidney to respond to ADH.

50
Q

What is syndrome of inappropriate ADH (SIADH)?

A

Excessive ADH, often from tumors.