Control & Abnormalities of Body Water Flashcards
How much of the body’s weight is composedof water?
60% body weight = body water
How much of the body water is composed of ICF and ECF?
Intracellular water: 40% body weight (ICFV)
Extracellular water: 20% body weight (ECFV)
60 40 20 rule
How does osmoregulation occur?
Osmosis determines movement of fluid between ICFV and ECFV
What does a change in body [Na] suggest?
Changes in plasma [Na] suggest excess or deficit of body water
What is hyponatremia?
Decreased [Na] < 140
What is hypernatremia?
Increased [Na] > 140
Which electrolyte determines the ECFV osmolarity?
Plasma [Na] (with associated anions) is the main determinant of ECFV osmolality
What is osmolality?
Osmolality relates to the number of particles per unit volume of fluid [technical note]
What is the difference between osmolality and osmolarity?
osmolality: per kg water
osmolarity: per litre solution
How can we estimate the plasma osmolality?
Plasma osmolarity in mOsm L-1 can be estimated from:
2[Na] + 2[K] + [glucose] + [urea]
What is the normal plasma osmolality?
Normal plasma osmolality 275-295 mOsm kg-1
In terms of osmolality what is hypernatremia?
Hypernatremia always means hyperosmolality
How does hyponatremia affect osmolality?
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]
What are osmoreceptors?
sensory receptors located in hypothalamus sense changes in osmolality of ECFV
What does an increase in osmolality stimulate?
Thirst
Secretion of vasopressin (ADH)
What is ADH?
ADH - vasopressin is the osmoregulation hormone
What is the role of ADH?
Regulates plasma osmolality primarily by controlling water excretion and reabsorption (rather than sodium excretion/reabsorption)
How is the excretion of water and solutes carried out?
Excretion of water is normally regulated independently of solute excretion
What is the lowest [urine] able to be secreted?
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
What effect does ADH have on the collecting duct?
ADH makes the collecting duct more permeable to water
Explain how ADH allows more water to be reabsorbed?
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
Where is ADH secreted?
distal tubule and collecting duct
Outline the mechanism of ADH action
- ADH binds to Type 2 basolateral membrane receptors
- Receptor activates cAMP secondary messenger system
- Cell inserts AQP2 water channels into apical membrane
- Water is reabsorbed by osmosis back into blood
- Small volume of conc urine produce
What 2 major physiological systems, regulate the secretion of ADH?
Via osmoreceptors due to changes in osmolality or via (short term) baroreceptors due to large drops in arterial BP
How do osmoreceptors regulate ADH secretion?
Osmoreceptors in hypothalamus are constantly monitoring plasma and ICF osmolarity
They send signals to neurosecretory cells of hypothalamus releasing ↑↓ADH
What can cause blood volume depletion?
haemorrhage, loss of BP sufficient to stimulate ADH
What is the first line of defence against dehydration?
Thirst is the first (and highly effective) line of defence against dehydration
What are the 2 thirst responses?
Hyperosmotic thirst (↑osmolarity) Hypovolemic thirst (drop in BV)
What is the plasma osmolality maintained by the kidneys?
Normally, the vasopressin system (hypothalamo-piuitary renal) can maintain plasma osmolarity at about 285 mOsmol L-1 (275-295) during variable water intake
What is the solute load?
metabolic waste product in solute form excreted by kidneys
Estimated as 10 x BW in kg (e.g., 600 mOsmol for 60 kg person)
How does volume of urine effect the solute load excreted?
High concentration requires small vol.
Low concentration requires a large volume of urine to excrete the same amount
What can cause excess water?
Excessive water intake
Impairment in renal water excretion
How does water depletion occur?
Insufficient water intake
Impairment in renal water reabsorption
How does abnormal body water volume lead to hyponatremia?
Continued water intake with failure to surpress ADH can lead to water overload and hyponatremia
Give examples of conditions causing hyponatremia
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)
What is Addison’s disease?
primary adrenal failure
What does Addison’s disease cause a loss of?
Cortisol
Androgens
Aldosterone
High ACTH
What may be the cause of primary adrenal failure?
Causes are usually autoimmune
What is the consequence of a loss of cortisol in Addison’s disease ?
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.
What is the consequence of excessive ADH secretion?
Excessive ADH reduces urinary water excretion Results in a state of water excess and:
Low plasma sodium
Low plasma osmolality
High urine osmolality
What are the major causes of inappropriate ADH secretion?
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
When may dehydration occur?
Water depletion from decreased intake of water can occur in Infants Elderly (demented, stroke etc.) coma patients Individuals with no access to water
What can cause increased water loss via kidneys?
Diabetes mellitus
Impairment in ADH release and/or action
What is Polydipsia & Polyuria ?
Complaint of frequent urination and drinks large volumes of water frequently
Plasma sodium 140 - 150 mmol/L
Urine Osmolality < 100 mosmol/Kg
What is central diabetes insipidus?
Central DI - lack of ADH secretion
Genetic mutations
Head trauma
Hypothalamus / pituitary region injury
What is nephrogenic diabetes insipidus?
Nephrogenic DI - impaired response to ADH ADH receptor mutation Mutation of ADH- dependent H₂O channels Renal Disease Drugs; e.g. Lithium
