Regulation of Body Fluid Osmolarity Flashcards

1
Q

T or F. a change in TBW is uniformly distributed in different body fluid compartments resulting in uniform change in fluid osmolarity in different compartments

A

T. Because cell membranes are highly permeable to water,

So an excessive water intake would increase TBW resulting in a decrease in body fluid osmolarity in different compartments and vice versa

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2
Q

How does the kidney respond to a decrease in fluid osmolarity?

A

by increasing water excretion in the urine.

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3
Q

How does the kidney respond to a change in fluid osmolarity?

A

This is a centrally regulated process.

ADH secreted by the pituitary gland regulates water reabsorption in kidney. Thirst center regulates water intake.

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4
Q

What is the normal intake/production of water daily?

A

Normal daily water intake is about 2000 ml (1500 drinking and 500 food) and 400 ml is produced in the body during metabolic processes.

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5
Q

What is the normal distribution of water output daily?

A

urine-1500ml
breathing-400ml
skin-400ml (burn can drastically increase)
feces-100ml

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6
Q

Does the kidney have a high capacity to excrete water?

A

Yes, Excessive water driniking or lack of ADH may increase GFR by 10% which is equal to 18 L/day.

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7
Q

Eqn for plasma osmolarity

A

2[Na+] + glucose concentration in mg/dl divided by 18 + BUN in mg/dl divided by 2.8.

normal is ~285mOsm
Na 137, glucose 100, and BUN 15

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8
Q

Changes in osmolarity is sensed by what?

A

osmoreceptors. The Osmoreceptors on supraoptic and paraventricular nuclei of the hypothalamus are stimulated by an increase in body fluid osmolarity.

Increase in osmolarity also stimulates osmoreceptors in the thirst center I the hypothalamus. The result is change in behavior encouragig to drink more water.

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9
Q

What does activation of the supraoptic and paraventricular nuclei of the hypothalamus cause?

A

Activation at the cell body of supraoptic nerves transmits signal to the nerve ending that is located in the posterior pituitary gland. The final cellular signal in the nerve ending is increase in intracellular calcium. Elevated intracellular calcium stimulates membrane fusion of ADH containing vesicles resulting in exocytosis of ADH into ECF.

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10
Q

What does ADH do?

A

ADH acts on the CD epithelial cells and increases water reabsorption.

Increase in water reabsorption corrects the osmolarity back to normal.

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11
Q

What is the composition of ADH?

A

small peptide consisting of 9 amino acids with a MW of 1100 daltons.

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12
Q

T or F. The basolateral membranes of the CD epithelial cells have the receptors for vasopressin

A

T.

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13
Q

How is ADH released from the pituitary transported to the kidney?

A

By circulation. It binds to vasopressin receptors on the BL membrane and activates the intracellular signaling. It first activates the adenylate cyclase that converts ATP into cAMP.

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14
Q

What does increased cAMP in the CD epithelial cells stimulate?

A

cAMP activates protein kinase A which phosphorylates vesicles containing aquaporin-2 in their membranes and makes them fuse to plasma membrane on the luminal side, thus increases water permeability of the cells.

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15
Q

How quick is this whole process?

A

This is a rapid process, takes less than 10 min to increase water permeability once the plasma ADH level is increased

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16
Q

What are the types of vasopressin receptors?

A

There are 3 types of vasopressin receptors, V1, V2 and V3. It is the V2 receptors on the basolateral membrane that is involved in cAMP production and aquaporin translocation to luminal membrane.

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17
Q

What do V1 and V3 do?

A

V1 and V3 receptors are G-protein coiupled receptors. V1 receptors seem to present in the luminal membranes, but its function is unclear at this point.

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18
Q

What happens to ADH once it functions?

A

ADH released by stimulation of hypothalamus is rapidly degraded in the PT and liver, thus avoiding sustained presence of high plasma ADH. Rapid degradation help bring the ADH level back to normal.

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19
Q

Does increase in plasma osmolarity lead to concentrated or diluted urine?

A

concentrated. Make sure you know how

Urinary osmolarity can go as high as 1200 mOM.

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20
Q

Describe the relationship between plasma AVP (y) and plasma osmolality (x).

A

up to pOsm of 270, AVP is negligible. Above 270 mOsM osmolarity ADH level increases proportionally to reach maximum of 18 pM at 290 mOsM plasma osmolarity. Above this plasma osmolarity, AVP levels will not increase any more.

21
Q

In addition to plasma osmolarity, ADH secretion is also regulated by plasma volume. How?

A

A decrease in ECFV by 1.5 L (from normal) has only a little effect on ADH level. But, further decrease in ECFV increases plasma ADH concentration, which can be as high as 50 pg/ml.

Therefore, the threshold for ADH secretion by reduction in ECFV is very high.

22
Q

Greater than 10-15% decrease in ECFV is required to have a strong increase in plasma ADH.

A

Second, a 25% decrease in ECFV can increase plasma ADH level to 50 pg/ml, which is almost 3 fold higher than the highest concentration achieved by osmolarity changes.

23
Q

Can osmolarity and volume be reduced at the same time?

A

Yes, A clinical condition that may reflect such a situation is of severe decline in ECFV due severe diarrhea, but with reduced plasma osmolarity due to loss of salts in diarrhea.

Based on osmolarity there should reduced plasma ADH causing diuresis. But, that would result in further reduction of volume. On the other hand, reduction of plasma volume should increase plasma ADH and increase water reabsorption. So, which effect prevails?

Under condition of severe loss of ECFV its effect on ADH release overrides osmolarity effect on ADH secretion. In other words, it does not matter what the osmolarity is at low ECFV, the AVP level rises high.

24
Q

How does excessive vomiting lead to hypoatremia?

A

Assume the lid loss in vomit is isotonic.

The ECFV depletion (but not osmolarity because we assume no change) is large enough to stimulate ADH release.

ADH indcues concentration of urine and dilution of plasma.

Therefore body water is conserved and the ECFV is increased.

The result is reduced osmolarity and hyponatremia

25
Q

What are some clinical signs of hyponatremia?

A

lethargy, hyporeflexia and mental confusion

26
Q

Treatment for persistent vomiting?

A

infusion of isotonic saline.

27
Q

A common symptom of decreased ability to concentrate urine is what?

A

A common symptom of decreased ability to concentrate urine is nocturia, that is frequent urination during night

28
Q

The ability of kidneys to dilute or concentrate urine depends on what?

A

the rate at which they excrete water in relation to solute.

So, to assess the ability of kidney to concentrate or dilute urine requires us to first quantitate the rate of excretion of solute. The parameter used for this is osmolar clearance

29
Q

What is the eqn for osmolar clearance?

A

Cosm= UF*(Uosm/Posm)

30
Q

What is normal osmolar clearance?

A

2 ml/min +- 0.5

Represents the rate at which solute is removed from plasma and excreted in urine

31
Q

What is water clearance?

A

Water clearance is how much water is cleared in urine at a given time. The difference between osmolar clearance and water clearance is the “free water clearance.

32
Q

Eqn for free water clearance.

A

Ch20= UF-Cosm

So if urine osmolarity is less than plasma osmolarity, there will be a positive free water clearance, that is dilution of urine and plasma osmolarity increases

On the other hand, if urine osmolarity is greater than plasma osmolarity, there will be a negative free water clearance, which means urine is being concentrated and reduction of plasma osmolarity

33
Q

Here is a numerical example of free water clearance under condition of hypo-osmolar plasma

A

Assume plasma is dilute: 270 mosml/L (plsma AVP is undetectable) and RPF is 0.69 L/min

Mass osmolar flow is 0.69 x 270 = 186.3 mOsmol/min

Assume urine is dilute: 50 mOsml/L and urine flow is 12 ml/min

Mass osmolar flow is 0.012 x 50 = 0.6 mOsm/min

Renal venous flow:
RPF = 690-12 = 678 ml/min
Osmolar flow = 186.3-0.6 = 185.7 mOsm/min

Venous plasma osmolarity = 185.7/0.678 = 274 mOsM that is plasma osmolarity is increased by 4 mOsM

The free water clearance is 12 ml/min of UF times (1 minus 50 mOsm/L of urine osmolarity divided by 270 mOsm/L plasma osmolarity); 9.78 ml/min.

34
Q

Here is a numerical example of free water clearance under condition of hyper-osmolar plasma

A

Assume plasma is hyperosmolar: 300 mosml/L (plsma AVP is high) and RPF is 0.69 L/min
Mass osmolar flow is 0.69 x 300 = 207 mOsm/min

Assume urine is concentrated: 1200 mosml/L and urine flow is 0.5 ml/min
Mass osmolar flow is 0.0005 x 1200 = 0.6 mOsm/min

Renal venous flow:
RPF = 690-0.5 = 689.5 ml/min
Osmolar flow = 207-0.6 = 206.4mOsm/min
Venous plasma osmolarity -= 206.4/0.6895 = 299.3 mOsM that is decrease by 0.7 mOsM

The free water clearance is 0.5 ml/min of UF times 1 minus 1200 mOsm/L of urine osmolarity divided by 300 mOsm/L plasma osmolarity; -1.5 ml/min.

Human kidney is more efficient in clearing water than conservation

35
Q

Renal medullary osmolarity is high surrounding the LOH and there is an osmolarity gradient from the cortical end to the papillary end. What is the significance?

A

Due to the osmotic gradient between the TF and medullary IS, water and NaCl are reabsorbed which then to carried to blood by the vasa recta.

36
Q

How is the hyperosmolarity gradient is developed and maintained in the medulla?

A

The permeability characteristics of different segments of DT play important role in this.

Thin descending limb is highly water permeable, but impermeable to NaCl

Thin ascending limb is impermeable to water. It is permeable to NaCl, but there is no active transport mechanism for it.

Thick ascending limb is also impermeable to water but NaCl is absorbed by active transport mechanism.

The DCT and CD are permeable to water depending on ADH level and Na is transported by active transport mechanism.

The CD in the inner medulla is also highly permeable to urea in addition to being permeable to water depending on ADH level and Na is transported by active transport mechanism.

37
Q

Features of kidney responsible for development of medullary hyperosmolarity

A
  1. Special anatomical arrangement of loop of Henle and vasa recta and peritubular capillaries.
    Loop like arrangement of LOH and vasa recta
  2. Active transport of Na+ and co-transport of K+ and Cl- out of thick ascending limb into medullary ISF
    Capable of creating 200 mOsm gradient between tubule and ISF
  3. Active transport of Na+ out of collecting duct into ISF
  4. Passive diffusion of urea from inner medullary collecting duct into medullary ISF
  5. Diffusion of only small amounts of water from medullary tubules into medullary interstitium
38
Q

Let us say in step 1, the TF and ISF are isoosmolar that is 300 mOsM all over.

In step 2, the active transport mechanism in the thick ascending limb of LOH creates an osmolarity gradient with 200 mOsM TF and 400 mOsM ISF.

In step 3, water is absorbed in the thin descending limb due to the osmotic gradient created by the active of Na, concentrating the TDL.

A

In step 4, as the fluid in the thin descending limb flows downwards an osmolarity gradient is created, as it becomes more concentrated

In Step 5, as the fluid from the descending limb flows upwards into the ascending limb the active transport of Na creates an new gradient between TF and ISF.

In step 6, water is transported in the descending limb to match the new osmolarity gradient.
Repeating the steps 4-6 results in development of a stable osmolarity gradient.

39
Q

Does urea play an important role in maintenance of medullary hyperosmolarity?

A

Yes, it contributes to at least 40% of medullary ISF hyperosmolarity.

40
Q

What segments are permeable for reabsorption of urea?

A

The thin limbs of LOH are only slightly permeable to urea.

The thick ascending limb, the DCT and the cortical CD are impermeable to urea.

So urea is concentrated by the time it reaches the inner medullary CD, which has very high permeability to urea.

41
Q

So how is urea absorbed into the medullary ISF?

A

by simple diffusion.

As the permeability of thin limbs of LOH to urea is low, a high urea concentration is maintained in the inner medullary ISF, which contributes to hyperosmolarity.

42
Q

Why do the medullary capillaries not wash out the medullary hyperosmolarity?

A

First, the medullary blood flow is low.

Only 1-2% of renal blood flow reaches inner medullary region. The flow rate is only 50 ml/min.

Second, due to the loop structure of the vasa recta, it serves in counter current exchange. The plasma osmolarity in the descending vasa recta does increase similar to the medullary ISF osmolarity gradient. But, when the blood flows upwards in the ascending vasa recta the plasma osmolarity drops to normal osmolarity. Therefore, there no net clearance of medullary hyperosmolarity.

43
Q

What does diabetes insipidus result in?

A

High rates of production of dilute urine

NOTE: there are two types- central and nephrogenic

44
Q

What is central DI?

A

Pituitary gland fails to release AVP - rare congenital

Patients get dehydrated very quickly

45
Q

What is nephrogenic DI?

A

Collecting ducts do not respond to AVP

46
Q

Causes of nephrogenic DI?

A
  • V2 receptor mutation
  • Aquaporin-2 mutation
  • Drugs: lithium, tetracycline
47
Q

What is polydipsia?

A

Psychiatric condition characterized by obsession of water drinking leading to hyponatraemia (water intoxication) and potentially coma and death

48
Q

How does nicotine affect ADH?

A

increases it

49
Q

How does alcohol affect ADH?

A

decreases it- plasma osmolarity will increase BUT it is freely permeable through the plasma membrane so it won’t increase it