Regulation of Body Fluid Flashcards

1
Q

What determines CO?

A

ECFV determines the plasma volume. Plasma volume determines the circulatory filling pressure and therefore the cardiac output.

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2
Q

What determines the ECFV?

A

the total body Na content

ECFV= Amount of ECF Na+/ [Pna]

where [Pna]= plasma Na conc.

So, at constant plasma Na concentration, ECFV is proportional to total body Na.

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3
Q

Why doesnt plasma Na concentration reflect the ECFV?

A

because plasma Na is always kept constant by ADH-mediated regulation of water reabsorption in the kidney.

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4
Q

T or F. Plasma Na is altered only when gain or loss of Na exceeds the thirst mechanism and kidney’s ability to correct it.

A

T.

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5
Q

Therefore, in order to maintain a constant ECFV, we need to maintain a constant total body Na content. How do we do this?

A

To maintain a constant total body Na content we need to match daily Na intake with daily Na output.

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6
Q

What is the daily Na+ intake?

A

8-15g/day or

150-250 mEq.

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7
Q

What happens if you do not match Na intake with its output from the body?

A

If you retain 150 mEq of Na in the body, you will retain 1 L of water in the body to maintain isotonicity.

This will increase the BW by 1 Kg or 2.2 lbs. Thus, a change in BW over a short period is an indicator of change in Na balance.

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8
Q

The patients with renal failure and under dialysis are required to monitor their BW on a daily basis.

A

In fact, one can use the values of BW changes to calculate how much dialysis might be required.

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9
Q

So, the daily Na intake needs to be matched with equal amount of Na output from the body. How is this done?

A

80-90% of daily intake of Na is excreted in the urine. This is tightly regulated by homeostatic mechanism.

0.5-10% is excreted in the feces. This output is higher under conditions of diarrhea or vomiting.

0-20% is excreted via skin by sweat and insensible perspiration.

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10
Q

What things can cause Na+ imbalance?

A

Pathophysiologic conditions such as diarrhea, excessive sweating and drugs such as diuretics

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11
Q

How much Na (mEq/day) is filtered through the glomerulus daily?

A

180 L/day of GFR times 139 mEq/L of plasma Na concentration is equal to 25,000 mEq of Na/day

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12
Q

How much Na is reabsorbed in the PT? Ascending limb of the LOH? DCT?

A

64% is reabsorbed which is approximately 16,000 mEq/day.

7000 mEq is reabsorbed in the ascending limb of LOH and 2000 mEq in the DCT.

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13
Q

How much Na is reabsorbed in the CD?

A

About 1750 mEq absorbed from the CD.

So, 150-250 mEq/day is excreted in the urine which is equal to 150-250 mEq of daily intake.

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14
Q

How can changes in the ECFV be monitored?

A

By monitoring vital signs in the clinic.

Hypovolemia is associated with hypotension both systolic and diastolic, especially orthostatic hypotension. The pulse is increased and low body temperature. Burn patients also show hypovolemia due to increased endothelial permeability and edema

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15
Q

What things can cause ECFV expansion?

A

hypervolemia may be caused chronic renal failure, heart failure due to excessive salt and water retention

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16
Q

Edema due to ECFV expansion requires how much volume retention?

A

2-3L

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17
Q

What are some other signs of ECFV expansion?

A
  • presence of S3 gallop

- Distension of EJV

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18
Q

Can edema occur under conditions of normal or low ECFV? How?

A

Yes,

Hypoalbuminemia caused by liver disease or nephrotic syndrome can cause edema without change in ECFV.

Other conditions such as burn injury may increase endothelial permeability and flux of whole plasma into ISF compartment.

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19
Q

What is the site of albumin synthesis?

A

Liver is the site of albumin synthesis, which is compromised in liver disease.

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20
Q

The body rapidly responds to changes in plasma osmolarity. Explain

A

Following ingestion of 1 L of water the osmolarity of plasma and urine, urine flow rate and urinary solute excretion were measured.

Immediately after water consumption the plasma osmolarity is slightly reduced. The urine flow rate (more so) and solute output are quickly increased resulting drop in urine osmolarity.

The normal plasma osmolarity is restored back to normal by about 2 hours after water ingestion.

Thereore, water intake leads to diuresis and water balance and plasma osmolarity are restored very quickly

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21
Q

T or F. Unlike the renal water excretory response, renal Na excretory response is relatively slow and takes several days (2-4) to fix total body Na content.

A

T.

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22
Q

Explain why renal Na excretory response is relatively slow and takes several days to fix total body Na content.

A

If you consume 1 L of isotonic saline the balance is restored by diuresis and natriuresis, but it takes 2-4 days.

Regarding the graph, a subject, maintained in low salt diet was switched to high salt diet and the daily Na output was measured.

The graph shows that daily Na output was increased gradually over few days before the output matches the intake. When this subject was switched back to low salt diet the daily Na output decreased gradually over few days.

The changes in Na output correlated with the changes in the body weight.

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23
Q

Hypertension patients are recommended to cult salt intake, but is important to keep in mind that it will take few days prior to see the result of that.

A

Hypertension patients are recommended to cult salt intake, but is important to keep in mind that it will take few days prior to see the result of that.

24
Q

There are two types of patients: the salt sensitive and salt-insensitive. What happens to salt-insensitive patients who ingest large amounts of salt?

A

The salt-insensitive patients do not develop hypertension as the salt intake is quickly excreted by efficient homeostatic mechanisms.

Whereas salt sensitive patients do not clear the Na well and therfore develop hypertension, and therefore may required treatment with diuretics

25
Q

Many individuals maintain normal BP despite wide variation in their salt intake. Some are more sensitive to changes in Na intake.

A

Salt sensitive hypertensives have greater propensity to retain sodium in the presence of high Na intake and thus expand their ECFV and higher BP

26
Q

Changes in ECFV are sensed by what mechanically?

A

by stretch receptors and baroreceptors present in large veins, atria and arteries

27
Q

Name some stretch receptors that sense changes in ECFV.

A
  • neural stretch receptors
  • atrial stretch receptors
  • arterial baroreceptors
28
Q

How do neural stretch receptors work?

A

These are present in large veins, and they respond to mechanical stretch due to venous distention.

Stimulated nerves sends signal to pituitary gland to suppress ADH secretion into plasma.

29
Q

What does reduced plasma ADH cause?

A

Reduced plasma ADH suppresses water reabsorption in the DCT and CD and Na reabsorption in the thick ascending limb of LOH.

Net result is increased excretion of Na and water in the urine

30
Q

How do atrial stretch receptors work?

A

They are localized in atria and respond to distention. It sends signal via parasympathetic fibers to a variety of centers to suppress ADH secretion, and sends signals via synthetic firing to kidney and cardiovascular centers.

Distention of atria also secrete atrial natriuretic peoptide of ANP. ANP stimulates renal Na excretion.

31
Q

How do arterial baroreceptors work?

A

They are located in arteries and respond to increase in arterial blood pressure. They send signals to pituitary gland and suppress ADH secretion and regulate Na excretion.

32
Q

ECFV is maintained at a normal level by regulating Na excretion in the kidney. Name some regulators of Na excretion.

A
  1. Changes in GFR
    - increased GRF= increased Na+ excretion
  2. Aldosterone = more Na+ reabsorption in DT and CD
  3. ANP= decreased Na+ reabsorption
  4. RAAS: decreased ECFV = Na+ reabsorption
  5. Others: sympathetic nerves, prostaglandins, etc.
33
Q

How does GFR regulate Na excretion?

A

A change GFR can result in proportional change in filtered Na and therefore a significant change in Na excretion in the urine.

Small changes in GFR can be undetectable, but it still has significant impact on Na excretion due to proportional increase in Na load in the LOH.

34
Q

Example of last card.

A

For example, if GFR is increased by 10% the total filtered Na will increase from 25,000 mEq/day to 27,500 mEq/day.

That is 9900 mEq/day instead of 9000 mEq/day of Na delivered into LOH. Therefore, larger amounts passes through DCT and CD.

35
Q

What is pressure natriuresis?

A

A feedback regulatory mechanism for an increase in arterial pressure. If the systolic BP is increased by 50% there will be a 3-5 fold increase in Na excretion in the urine, thus reducing ECFV and reduction of BP.

this is entirely a kidney phenomenon

36
Q

T or F. Smaller changes in BP will not significantly change GFR

A

T, due to auto regulation.

However, an abnormal pressure natriuresis may contribute to chronic hypertension

37
Q

Example

A

Ingestion of large dose of Na+ occurs frequently in the modern diet, ex. pizza. This increase total body Na and therefore ECFV as osmoregulation retain more water and thirst mechanism is stimulated. This would increase arterial pressure. Kidney responds to it by increasing GFR and increase in Na excretion. The result is reversal of ECFV back to normal.

38
Q

Is pressure natriuresis in an isolated kidney quick or slow?

A

slow and gradual (graph is concave up).

Small changes in pressure is unlikely to cause significant change in sodium excretion.

39
Q

Is pressure natriuresis in the intact system quick or slow?

A

In the intact system the pressure effect is dramatically more sinsitive (almost vertical relationship at 100 mm Hg)

Small changes in pressure at physiologic condition results in dramatic change in Na excretion.

This Indicates that there is modulation of pressure natriuresis by some extrinsic factors. Renin angiotensin system is likely involved in this potentiation of pressure natriuresis. When BP is increased, the RAS system is shut down and becomes more sensitive to pressure natriuresis.

40
Q

What does aldosterone do?

A

It stimulates Na+ reabsorption and K secretion in the DCT and CD only.

The effect of aldosterone is slow as it involves changes in gene expression and not likely to play role in rapid changes in Na excretion in response to Na load.

41
Q

What causes aldosterone release from the adrenal cortex?

A

hyperkalemia and angioIIand is inhibited by high PNa+

42
Q

How does aldosterone work?

A

It is permeable to cell membranes and binds to cytoplasmic and nuclear receptors to influence gene expression, namely:

1) Increases no. of open Na+ channels in apical membrane of DCT and CD. Increase NaCl co-transporter
2) Increased synthesis of NKA (increase Na+ reabsorption and K+ secretion)
3) Increased synthesis of the Kreb’s cycle enzymes via increased ATP synthesis

43
Q

Where does ANP work?

A

both the DT and the renal arterioles.

Only 3-5 fold increase in Na excretion

44
Q

What does ANP do specifically?

A

It increases GFR by dilating afferent arterioles and causing constriction of efferent arterioles and inhibits Na+ reabsorption and therefore, increases urinary Na excretion.

It inhibits Na-Cl cotransporter in the DCT and Electrogenic Na channels in CD by phosphorylation resulting in increased excretion of Na in urine.

It also inhibits secretion of aldosterone in adrenal cortex and inhibits secretion of renin, all leading to decreased Na reabsorption and increased Na excretion in the urine.

45
Q

How is the RAS system is regulated and what is its effect on ECFV?

A

Renin-angiotensin system responds to drop in BP and reduction in ECFV.

46
Q

What does a drop in BP and reduction in ECFV do?

A

A drop in ECFV stimulates juxta glomerular cells in the renal arterioles to secrete renin into the circulation.

Renin is a protease and generates angiotensin I by proteolytic action on serum a2-globulin.

47
Q

How does Ang II increase Na reabsorption in the kidney?

A

Two mechanisms:

First it directly activataes NHE in the PT to increase Na reabsorption.

Second it stimulates aldosterone secretion from the adrenal cortex, which in turn increases Na reabsorption via Na channels in the DT.

The net result is expansion of ECFV.

48
Q

There are other factors that may influence renal Na reabsorption and regulation of ECFV. Name some.

A

Kidney is innervated with sympathetic nerve fibers.

Stimulation of sympathetic nerves decreases GFR and increases Na reabsorption in the PT.

49
Q

How do prostaglandins, bradykinin, and dopamine produced in the kidney affect renal Na reabsorption? Ouabain like factor?

A

stimulate diuresis and natriuresis

produced in atrium- same effect

Ouabain like factor inhibits NKA

50
Q

Overall response to hypovolemia

A

Significant hypovolemia stimulates ADH secretion that increases water reabsorption in the kidney. It can also stimulates Na channels in the DT.

Another important regulatory mechanism that responds to hypovolemia is renin-angiotensin system. As mentioned earlier, Ang II increase Na reabsorption in the PT (by decreasing cAMP and activates NHE) and increase aldosterone production.

Eventually- Sympathetic stimulation and norepinephrine release is another regulatory mechanism that targets arterioles and mesangial cells in the glomerulus and JGA causing reduction of GFR. It also increase NA reabsorption in the PT.

51
Q

What does AVP do?

A

activates Enac in DCT and CD and increases Na reabsorption that is important driving water reabsorption by AVP.

52
Q

What does ADH do?

A

activates luminal Na channel in CD and DT to increase Na reabsorption

53
Q

An increase in ECFV by 3L results in edema. A patient with jaundice showed edema event though the neck vein was flat. Explain.

A

liver disease causes decreased albumin synthesis, leading to reduced plasma protein and reduced oncotic pressure

54
Q

A change in BW in a short period of time is an indicator of imbalance in body water content. In a subject, the BW was increased at 24 hr after switching from low to high salt diet. In another subject, there was no change in BW after 24 hrs after ingestion of 2L of water. Why?

A

the body can respond to changes in water much more quickly via ADH within about 1-2 hours

55
Q

A patient is inadvertently given 2L of isotonic saline over a period of 4 hrs. This infusion should cause an increase in what?

A

ANP