Control & Abnormalities of Body Water

Question 1

How much of the body’s weight is composedof water?

Answer 1

60% body weight = body water

Question 2

How much of the body water is composed of ICF and ECF?

Answer 2

Intracellular water: 40% body weight (ICFV)
Extracellular water: 20% body weight (ECFV)
60 40 20 rule

Question 3

How does osmoregulation occur?

Answer 3

Osmosis determines movement of fluid between ICFV and ECFV

Question 4

What does a change in body [Na] suggest?

Answer 4

Changes in plasma [Na] suggest excess or deficit of body water

Question 5

What is hyponatremia?

Answer 5

Decreased [Na] < 140

Question 6

What is hypernatremia?

Answer 6

Increased [Na] > 140

Question 7

Which electrolyte determines the ECFV osmolarity?

Answer 7

Plasma [Na] (with associated anions) is the main determinant of ECFV osmolality

Question 8

What is osmolality?

Answer 8

Osmolality relates to the number of particles per unit volume of fluid [technical note]

Question 9

What is the difference between osmolality and osmolarity?

Answer 9

osmolality: per kg water
osmolarity: per litre solution

Question 10

How can we estimate the plasma osmolality?

Answer 10

Plasma osmolarity in mOsm L-1 can be estimated from:

2[Na] + 2[K] + [glucose] + [urea]

Question 11

What is the normal plasma osmolality?

Answer 11

Normal plasma osmolality 275-295 mOsm kg-1

Question 12

In terms of osmolality what is hypernatremia?

Answer 12

Hypernatremia always means hyperosmolality

Question 13

How does hyponatremia affect osmolality?

Answer 13

Hyponatremia (usually) means hypo-osmolality body fluids

hypernatremia does not mean too much Na; it means too little water - deficit of water causes increase in [Na]

Question 14

What are osmoreceptors?

Answer 14

sensory receptors located in hypothalamus sense changes in osmolality of ECFV

Question 15

What does an increase in osmolality stimulate?

Answer 15

Thirst

Secretion of vasopressin (ADH)

Question 16

What is ADH?

Answer 16

ADH - vasopressin is the osmoregulation hormone

Question 17

What is the role of ADH?

Answer 17

Regulates plasma osmolality primarily by controlling water excretion and reabsorption (rather than sodium excretion/reabsorption)

Question 18

How is the excretion of water and solutes carried out?

Answer 18

Excretion of water is normally regulated independently of solute excretion

Question 19

What is the lowest [urine] able to be secreted?

Answer 19

The weakest [urine] that can be excreted will always equal the [fluid] reached at the DCT as no ADH present to insert water channels - CD impermeable to water

Question 20

What effect does ADH have on the collecting duct?

Answer 20

ADH makes the collecting duct more permeable to water

Question 21

Explain how ADH allows more water to be reabsorbed?

Answer 21

ADH binds to TYpe 2 basolateral receptors
Aquaporin channels are inserted in the luminal cell membranes allowing water to be reabsorbed - small volume of concentrated urine formed

Question 22

Where is ADH secreted?

Answer 22

distal tubule and collecting duct

Question 23

Outline the mechanism of ADH action

Answer 23

1. ADH binds to Type 2 basolateral membrane receptors
2. Receptor activates cAMP secondary messenger system
3. Cell inserts AQP2 water channels into apical membrane
4. Water is reabsorbed by osmosis back into blood
5. Small volume of conc urine produce

Question 24

What 2 major physiological systems, regulate the secretion of ADH?

Answer 24

Via osmoreceptors due to changes in osmolality 
or via (short term) baroreceptors due to large drops in arterial BP

Question 25

How do osmoreceptors regulate ADH secretion?

Answer 25

Osmoreceptors in hypothalamus are constantly monitoring plasma and ICF osmolarity They send signals to neurosecretory cells of hypothalamus releasing ↑↓ADH

Question 26

What can cause blood volume depletion?

Answer 26

haemorrhage, loss of BP sufficient to stimulate ADH

Question 27

What is the first line of defence against dehydration?

Answer 27

Thirst is the first (and highly effective) line of defence against dehydration

Question 28

What are the 2 thirst responses?

Answer 28

``` Hyperosmotic thirst (↑osmolarity) Hypovolemic thirst (drop in BV) ```

Question 29

What is the plasma osmolality maintained by the kidneys?

Answer 29

Normally, the vasopressin system (hypothalamo-piuitary renal) can maintain plasma osmolarity at about 285 mOsmol L-1 (275-295) during variable water intake

Question 30

What is the solute load?

Answer 30

metabolic waste product in solute form excreted by kidneys | Estimated as 10 x BW in kg (e.g., 600 mOsmol for 60 kg person)

Question 31

How does volume of urine effect the solute load excreted?

Answer 31

High concentration requires small vol. | Low concentration requires a large volume of urine to excrete the same amount

Question 32

What can cause excess water?

Answer 32

Excessive water intake | Impairment in renal water excretion

Question 33

How does water depletion occur?

Answer 33

Insufficient water intake | Impairment in renal water reabsorption

Question 34

How does abnormal body water volume lead to hyponatremia?

Answer 34

Continued water intake with failure to surpress ADH can lead to water overload and hyponatremia

Question 35

Give examples of conditions causing hyponatremia

Answer 35

Vomiting, diarrhoea Certain drugs (MDMA, ‘ecstacy’ promotes ADH secretion) Ectopic secretion of ADH (syndrome of inappropriate ADH secretion, SIADH) Hypocortisolism Primary adrenal insufficiency (Addison’s disease)

Question 36

What is Addison's disease?

Answer 36

primary adrenal failure

Question 37

What does Addison's disease cause a loss of?

Answer 37

Cortisol Androgens Aldosterone High ACTH

Question 38

What may be the cause of primary adrenal failure?

Answer 38

Causes are usually autoimmune

Question 39

What is the consequence of a loss of cortisol in Addison's disease ?

Answer 39

Lack of –ve feedback by cortisol => high CRH levels CRH ↑ VP secretion -> plasma dilution If severe hypotension (lack of effective circulating volume) VP secretion stimulated in response to arterial pressure drop, again diluting plasma This is why adrenal failure typically associated with hyponatremia.

Question 40

What is the consequence of excessive ADH secretion?

Answer 40

Excessive ADH reduces urinary water excretion Results in a state of water excess and: Low plasma sodium Low plasma osmolality High urine osmolality

Question 41

What are the major causes of inappropriate ADH secretion?

Answer 41

Tumour - ectopic production of ADH; small cell carcinoma of the lung CNS disturbance - enhanced ADH release; stroke, traume, infection Drugs - enhanced release of ADH or response to ADH, carbamazepine, prozac

Question 42

When may dehydration occur?

Answer 42

``` Water depletion from decreased intake of water can occur in Infants Elderly (demented, stroke etc.) coma patients Individuals with no access to water ```

Question 43

What can cause increased water loss via kidneys?

Answer 43

Diabetes mellitus | Impairment in ADH release and/or action

Question 44

What is Polydipsia & Polyuria ?

Answer 44

Complaint of frequent urination and drinks large volumes of water frequently Plasma sodium 140 - 150 mmol/L Urine Osmolality < 100 mosmol/Kg

Question 45

What is central diabetes insipidus?

Answer 45

Central DI - lack of ADH secretion Genetic mutations Head trauma Hypothalamus / pituitary region injury

Question 46

What is nephrogenic diabetes insipidus?

Answer 46

``` Nephrogenic DI - impaired response to ADH ADH receptor mutation Mutation of ADH- dependent H₂O channels Renal Disease Drugs; e.g. Lithium ```