47) Control and abnormalities of body water

Question 1

Describe the movement of water when water is added to the ECF?

Answer 1

• When water is added to the ECF (e.g. when we drink water) it will cause the ECF to expand and also will dilute the salts within the ECF
• This sets up an osmotic gradient which causes water to enter the cell via osmosis causing the ICF to expand

Question 2

Describe the movement of water when water is removed from the ECF?

Answer 2

• When water is removed from the ECF the salts become more concentrated and ECF would decrease
• As a result this creates an osmotic gradient and water by osmosis out of the cell from the ICF to the ECF

Question 3

Describe the movement of water when salt and water is added?

Answer 3

• First the ECF expands however with no change in concentration as salt and water is added
• As a result there is no osmotic gradient forming and so the added volume will be retained within the ECF causing it to expand

Question 4

How is water balance maintained in the body?

Answer 4

• Water intake must equal water loss

Question 5

What happens when there is water excess?

Answer 5

• When the intake of water is greater than water excretion it will decrease body fluid osmolality

Question 6

What happens when there is water deficit?

Answer 6

• When the intake of water is less than water excretion it will increase body fluid osmolality

Question 7

How is osmolarity of the ECF adjusted?

Answer 7

• The osmolarity of the ECF is adjusted by adding or removing water

Question 8

Where is water loss regulated in the body?

Answer 8

• Water loss is regulated at the renal tubules. This adjustment of water loss from the tubules allows for water balance to occur
• The amount of solute-free water excreted by the kidney can be varied.
• If water is in excess it will be corrected by increasing the amount of water in the urine resulting in a large volume of dilute urine
• If water is in deficit it will be corrected by decreasing the amount of water in the urine resulting in a small volume of concentrated urine

Question 9

Where is the urine/tubular fluid diluted/concentrated in the kidneys?

Answer 9

• Tubular fluid is concentrated in the medulla

- Tubular fluid is diluted in the ascending limb and DT

Question 10

Why is dilution and concentration of tubular fluid important?

Answer 10

• Tubular fluid eventually becomes urine
• If we want to conserve water we must concentrate the tubular fluid (and hence the urine) which is done in the medulla
• If we want to excrete water we must dilute the tubular fluid (and hence the urine) which is done in the ascending arm and DT

Question 11

How is the concentration of interstitial fluid in the medulla controlled?

Answer 11

• The counter-current mechanisms within the Loop of Henle and vasa recta
• Permeability to water in the descending limb
• Ion transporters in the ascending limb

Question 12

What happens to tubular fluid in the descending limb?

Answer 12

• The tubular fluid is more concentrated as it descends down the descending limb.
• This is because the descending limb is more permeable to water and so lets allows water to leave the tubules

Question 13

What happens to tubular fluid in the ascending limb?

Answer 13

• The tubular fluid becomes more diluted as it moves up the ascending limb
• This is because there are many active transport mechanisms of solutes out of the fluid leaves only the water behind
• However the ascending limb is impermeable to water so is retained in the tubular fluid

Question 14

How is osmolarity of the urine controlled?

Answer 14

• ADH is the osmoregulatory hormone
• As dilute urine from the collecting duct passes through the medulla it meets a strong osmotic gradient
• This causes the absorption of water from the tubule into the interstitial fluid
• In the absence of ADH the collecting duct becomes impermeable to water and so despite the osmotic gradient it is not reabsorbed
• Hence the urine excreted is maximally diluted
• An increase in ADH causes an increase in water permeability within the collecting duct
• This in turn causes an increase in water reabsorption in the collecting ducts which causes the urine excreted to be increasingly concentrated

Question 15

What is the mechanism by which ADH works?

Answer 15

• When ADH (vasopressin) is present in circulation (in the blood) it binds to vasopressin (V2) receptors
• cAMP activates intracellular secondary messengers which mobilises stored aquaporin from storage vesicles
• These are inserted into the liminal membrane of the principle cells within the collecting duct which allows water to enter the cell
• Due to the osmotic gradient water moves into the cell and from here enters general circulation in the plasma

Question 16

How is the number of aquaporin channels affected by concentration of plasma ADH?

Answer 16

• ## The amount of ADH binding to receptors regulates the amount of aquaporin channels present in the luminal membrane of the principle cells within the collecting duct

Question 17

What are V1 receptors?

Answer 17

• V1 receptors are a type of vasopressin receptors found on vascular smooth muscles which causes vasoconstriction
• However this effect only occurs at high levels of ADH

Question 18

What detects changes in extracellular fluid osmolarity?

Answer 18

• Osmoreceptors found in the hypothalamus

Question 19

How does ADH defend our body against dehydration?

Answer 19

• Net water loss causes increased osmolality in ECF.
• When this change in extracellular fluid concentration surpasses a threshold it is detected by osmoreceptors in the anterior hypothalamus
• They send these signals to magnocellular neurones of paraventricular and supraoptic nuclei of the hypothalamus
• The paraventricular and supraoptic nuclei release ADH from their axon terminals which are located in the posterior pituitary
• This ADH enters circulation of the blood stream

Question 20

How does plasma osmolality affect ADH?

Answer 20

• As ECF/plasma osmolality increases the amount of ADH secreted also increases

Question 21

How does hypovolemia affect concentration of ECF and urine?

Answer 21

• In a hypovolemic state (i.e. during haemorrhage or blood loss) there is a decrease in blood volume and pressure
• As blood pressure decreases a powerful stimuli will be fire which will increase the amount of ADH secreted
• This causes the urine to be concentrated and the ECF to be diluted
• This is considered the last line of defence against volume depletion

Question 22

How does thirst defend the body against dehydration?

Answer 22

• Net water loss causes increased osmolality in ECF.
• When this change in extracellular fluid concentration surpasses a threshold it is detected by osmoreceptors in the anterior hypothalamus
• Hypothalamic osmoreceptors can mediate a thirst sensation by projecting impulses to different centres (from those involved in the release of ADH)
• These centres give us a strong urge to drink
• Thirst can also be caused by a drop in blood volume/pressure or angiotensin 2 acting on the hypothalamus
• Thirst sensation is reduced by oropharyngeal and upper GI receptors when we drink

Question 23

How does body water levels cause hyponatremia and hypernatremia?

Answer 23

• If there is a water deficit ECF osmolality increases (called hyperosmolality) leading to hypernatremia
• If there is a water excess ECF osmolality decreases (called hypoosmolality) leading to hyponatremia

Question 24

How is the number of cations and anions in the ECF linked?

Answer 24

• Na+ is the main cation in ECF
• The principle of electroneutrality dictates that a molar equivalent of anions must also be present. This is mainly Cl- and HCO3-

Question 25

How do we calculate contribution of Na+ to ECF osmolality?

Answer 25

Contribution of Na+ to ECF osmolality = 2 x plasma [Na+]

This accounts for the anions that go with the Na+

Question 26

How can plasma osmolality be estimated?

Answer 26

plasma osmolality = 2[Na+] + 2[K+] + [glucose] + [urea]

Question 27

What is hypernatremia?

Answer 27

• (It does not mean too much Na+) It means too little water
• An increase in the Na+ concentration means there is too much Na relative to H2O (i.e. there is a water deficit)
• Hypernatremia means hyperosmolality of the ECF
• It is caused by any condition that is linked to fluid loss (as long as water loss is greater than loss of sodium)

Question 28

What are the two sub-types of the causes of hypernatremia?

Answer 28

• Extra-renal loss: Loss that does not occur through the kidney
• Renal loss: Loss that occurs through the kidney

Question 29

What are the causes of hypernatremia?

Answer 29

• Gain of Na+ (rare)
• Loss of water (common)
• Dehydration (Extra-renal loss)
• Infection: Can lead to increased loss via skin and lungs (Extra-renal loss)
• Osmotic diuresis (Renal loss)
• Diabetes insipidus (Renal loss)

Question 30

How does a gain in sodium lead to hypernatremia?

Answer 30

• Iatrogenic (caused by medical treatment)
• Excess ingestion (rare)
• Excess mineralocorticoid (aldosterone) activity (e.g. hyperaldosteronism) however causes mild hypernatremia

Question 31

How does dehydration cause hypernatremia?

Answer 31

• Lack of water intake can cause an excessive loss of water leading to hypernatremia

Question 32

How does infection lead to hypernatremia?

Answer 32

• Infection can cause excessive water loss via the skin and lungs
• Diarrhoea is not a cause of hypernatremia as in most cases water and salt is lost in equal amounts

Question 33

What is osmotic diuresis?

Answer 33

• When an osmotically active solute in the tubular fluid prevents the tubular fluid from being as dilute as it would normally be
• This impairs the osmotic gradient leading to a lack of water reabsorption

Question 34

How does diabetes insipidus cause hypernatremia?

Answer 34

• There is increased renal water loss as there is an inability to concentrate the urine
• This is caused by ineffective ADH.
• It can be classed as central diabetes insipidus (failure of secretion) or nephrogenic diabetes insipidus (lack of renal response)
• The symptoms are polydipsia (excessive thirst) and polyuria (excessive urination)
• Thirst mechanism is normally sufficient to prevent significant hypernatremia
• However hypernatremia will rapidly develop if access to water is restricted

Question 35

What is hyponatremia?

Answer 35

• It is too little water compared to Na+ and is always associated with hyperosmolarity of the ECF
• Continued ingestion of water without reducing ADH secretion will lead to hyponatremia

Question 36

What is hypoosmotic hyponatremia?

Answer 36

• It is sometimes considered ‘true’ hyponatremia
• ‘Pseudo’ hyponatremia occurs when other solutes are present in sufficient quantity that the proportional contribution of sodium to plasma osmolality is reduced

Question 37

How is Hyponatremia caused?

Answer 37

• Continued ingestion of water without reducing ADH secretion
• Syndrome of inappropriate ADH secretion (SIADH)

Question 38

What is Syndrome of Inappropriate ADH secretion (SIADH)?

Answer 38

• It is caused by damage to the CNS or ectopic production of ADH by a tumour
• It leads to hyponatremia and high urine osmolarity
• Because there is an inappropriate secretion of ADH too much water will be reabsorbed causing it to be highly concentrated

Question 39

How does hyponatremia also occur in a hypovolemic situation?

Answer 39

• When total Na+ increases and water is increased even more then we get hyponatremia in a hypovolemic state (e.g. congestive heart failure)

Question 40

How does congestive heart failure cause hyponatremia in a hypovolemic state?

Answer 40

• Perfusion of tissues is impaired and so the RAAS ‘thinks’ the body is hypovolemic leading to increased activation of RAAS
• This will increase Na+ and water retention leading to volume expansion (hypovolemia)
• Starling’s forces are altered as failing cardiac output will cause blood to back up at the venous end of the circulatory system thus raising central venous pressure
• This means net capillary filtration pressure will increase causing excess capillary filtration
• This excess filling will occupy interstitial fluid rather than plasma leading to oedema
• If the low volume signal is activated it will trigger ADH release which will dilute the ECF (hyponatremia)

Question 41

What is congestive heart failure?

Answer 41

• Congestive heart failure is a progressive condition where the left ventricle is increasingly unable to maintain cardiac output