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As a recap, list the percentages of the fluid compartments.

BODY WATER: 60% of the body weight

INTRACELLULAR WATER (ICFV): 40% of the body weight
EXTRACELLULAR WATER (ECFV): 20% of the body weight

Osmosis determines the movement of fluid between the ICFV and the ECFV.


What do changes in the plasma [Na] suggest?

Assuming there is no change in total body Na+, it suggests an excess or deficit of body water.


What is osmolality (and the difference between it and osmolarity)?

Osmolality relates to the number of particles per unit volume of fluid.

Osmolality: per kg of water
Osmolarity: per litre of solution


What is the relation between plasma [Na] and osmolality?

Plasma [Na] is 135-145 mmol/L
Plasma omsolality is 275-295 mOsm/kg

Hypernatremia always means hyperosmolality.
Hyponatremia (usually) means hypo-osmolality body fluids.

NOTE: hypernatremia doesn't mean too much Na, it means too little water. Total body Na is the same; it's the deficit of water that increases [Na].


How is the osmolality of the ECFV adjusted?

It is adjusted by osmoreceptors. They are sensory receptors located in the hypothalamus; they sense changes in osmolality of the ECFV.

An increase in osmolality stimulates:
- thirst
- secretion of ADH


Describe how ADH (vasopressin) acts as the osmoregulation hormone.

It regulates plasma osmolality primarily by controlling water excretion and reabsorption (rather than sodium excretion/ reabsorption).
The excretion of water is normally regulated independently of the excretion of solute.

This means that the kidney must be able to excrete urine that is either hyperosmotic (retaining water) or hypo-osmotic (excreting water) with respect to the ECF.


Describe the mechanism of action of ADH in the distal tubule and collecting duct.

1) Vasopressin binds to the membrane receptor.
2) The receptor activates the cAMP secondary messenger system.
3) The cell inserts AQP2 water pores into the apical membrane.
4) Water is absorbed by osmosis into the blood.


ADH secretion is regulated by two major physiological mechanisms.
What are they?

- baroreceptor input


What are the abnormalities of water balance?

- excessive water intake
- impairment of renal water excretion

- insufficient water intake
- impairment of renal water absorption


Continued water intake with failure to suppress ADH can lead to water overload and hyponatremia.
List some examples of such a scenario.

- vomiting, diarrhoea
- certain drugs (MDMA, 'ecstasy' promotes ADH secretion)
- ectopic secretion of ADH (syndrome of inappropriate ADH secretion, SIADH)
- hypocortisolism
- primary adrenal insufficiency (Addison's Disease)


Describe the Syndrome of Inappropriate ADH secretion (SIADH), and list some of its major causes.

Excessive ADH reduces the urinary excretion of water. This results in a state of water excess and:
- low plasma sodium
- low plasma osmolality
- high urine osmolality

Some major causes would be:
- TUMOUR: ectopic production of ADH, such as a small cell carcinoma of the lung
- CNS DISTURBANCE: enhanced ADH release, stroke, trauma, infection
- DRUGS: enhanced release of ADH or response to ADH, such as carbamazepine, Prozac, etc.


Describe the different instances in which water depletion (dehydration) can occur.

Water depletion from decreased intake of water can occur in:
- infants
- elderly (demented, stroke, etc)
- individuals in coma
- individuals with no access to water

Water depletion from increased loss of water through the kidney can occur in:
- diabetes mellitus
- impairment in ADH release and/or action


List some causes of Diabetes Insipidus.

Central Diabetes Insipidus (lack of secretion of ADH):
- genetic mutations
- head trauma
- disease of the hypothalamus/ pituitary region

Nephrogenic Diabetes Insipidus (impaired response to ADH):
- mutation of the ADH receptor
- mutation of the ADH-dependant H2O channels
- renal disease
- drugs, eg. lithium

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