Control and Abnormalities of Body Water Flashcards
How is the osmolarity of the ECF adjusted?
There are just two ways to change the concentration of a solution
Add/remove solute
Add/ remove water
The osmolarity of the ECF is adjusted by adding or removing water, not solute
This is accomplished by the kidney and the thirst mechanism
The kidney controls the fractional reabsorption of water from the tubular fluid
How does the renal tubule control osmoregulation?
Ability to vary amount of solute-free water in the urine through two important factors: -Concentration of interstitial fluid in medulla -Dilution of urine in ascending limb and distal tubule Urine concentration (and hence water excretion) can be varied between these limits
What is ADH, what does it do, and what situation would result in maximal ADH levels?
ADH is the osmoregulatory hormone
Urine entering the collecting duct is maximally dilute
Osmotic gradient for water reabsorption is large, but in the absence of ADH the collecting duct is impermeable to water
Maximally dilute urine is excreted (c. 50 mOsm/kg)
ADH is required to unlock the water permeability of collecting duct
With low levels of ADH, some water will be reabsorbed
Urine osmolality >100 mOsmol/kg is considered to signify the presence of ADH (albeit at low level)
Maximal ADH levels:
Limit of water reabsorption is set by osmolality of medullary interstitial fluid
This is the maximum urine concentration (and hence minimum water excretion) that can be achieved
What is the mechanism of ADH action?
Vasopressin V2 receptors on principal cells of CD
The receptor activates a cAMP second messenger system
Leads to an insertion of aquaporin 2 water channels into membrane through exocytosis of storage vesicles with those aquaporin-2 channels
V1 receptors on vascular smooth muscle – vasoconstriction but only significant with very high ADH levels
How does ADH defend against dehydration?
Net water loss increases ECF osmolarity
Normal range 285-295 mOsm/kg
Changes detected by osmoreceptors in anterior hypothalamus
Project to magnocellular neurons of paraventricular and supraoptic nuclei of hypothalamus
PVN and SON neurons release ADH from their axon terminals in posterior pituitary
Threshold for ADH release is 280-285 mOsm/kg
Above this range small changes in osmolality produce large changes in ADH secretion
ADH also stimulated by large (10-15%) decreases in blood volume/pressure
How does the mechanism of thirst defend against dehydration?
Net water loss increases ECF osmolarity
Normal range 285-295 mOsm/kg
Changes detected by osmoreceptors in anterior hypothalamus
Project to centres mediating thirst, drinking
Strong desire to drink when plasma osmolality ≥295 mOsm/kg
Oropharyngeal and upper gastrointestinal receptors reduce thirst on drinking
Thirst is also stimulated by
Large (10-15%) drops in blood volume/pressure
Angiotensin 2 acting on hypothalamus
Why is plasma [Na+] the main determinant of ECF osmolality?
Na+ is the main cation in ECF (135-145 mmol/L)
Principle of electroneutrality dictates that a molar equivalent number of anions must be present
Mainly Cl-, significant amount HCO3-, small contribution from other inorganic and organic anions
Contribution of Na+ to ECF osmolality is 2 x plasma [Na+]
e.g., 140 mmol/L Na+ + 140 mmol/L A- = 280
Plasma osmolarity in mOsm L-1 can be estimated from:
2[Na+] + 2[K+] + [glucose] + [urea]
How does disturbances of water balance show as disturbances of plasma [Na+}?
Water deficit
ECF osmolality increases (hyperosmolality)
Hypernatremia (Na > 145)
Water excess
ECF osmolality decreases (hypoosmolality)
Hyponatremia (Na < 135)
What is hypernatremia?
Remember: hypernatremia does not mean too much Na; it means too little water!
The total amount of Na in the body may be the same, or it may be decreased or it may be increased. The increase in Na concentration means there is a relative water deficit
Hypernatremia (Na > 145) always means hyperosmolality of ECF (too little water)
What are the causes of hypernatremia?
Logically there are just two possibilities:
Gain of sodium (rare)
Loss of water (common)
Iatrogenic- an unintended consequences of medical treatment e.g. incorrect administration of IV
Excess ingestion (rare)
Excess mineralocorticoid activity
-e.g., primary hyperaldosteronism (Conn’s)
-Hypernatremia, if present, is usually mild
How can loss of water cause hypernatremia?
Can occur in various conditions associated with fluid loss (but loss of water must be relatively greater than loss of Na)
Extra-renal losses:
Dehydration
Infection (increased losses via skin e.g. sweat and lungs)
Renal losses:
Osmotic diuresis e.g. in diabetes mellitus- glucose remaining in the urine(TF) means the dilution of the tubular fluid in the DT is going to be impaired and consequently the osmotic gradient and water reabsorption
Diabetes insipidus
What is diabetes insipidus?
Lack of effective ADH either
Renal water loss (inability to concentrate the urine)
Lack of effective ADH, either
Central (failure of secretion)
Nephrogenic (lack of renal response)
Presents with polydipsia (copious thirst) and polyuria ( a large volume of dilute urine)
The thirst mechanism alone is normally enough to prevent significant hypernatremia
But hypernatremia will rapidly develop if access to water is restricted
What is hypoosmotic hyponatremia?
Sometimes considered ‘true’ hyponatremia
‘Pseudo’ hyponatremia occurs when some other solute is present in sufficient quantity that the proportional contribution of sodium to plasma osmolality is reduced
True hyponatremia is associated with hypoosmolality: it signifies water excess
We will consider true (hypoosmotic) hyponatremia
How can ADH cause hyponatremia?
Continued ingestion of water without reducing ADH secretion will always lead to hyponatremia
Syndrome of inappropriate ADH secretion (SIADH)
Hyponatremia (reduced plasma osmolarity)
High urine osmolarity
Many causes, e.g.,
CNS damage/disease
Ectopic ADH production by tumour
Under normal conditions the function of ADH is osmoregulation
However, a large drop in arterial pressure is also a powerful stimulus for release of ADH interpreted as a low blood volume
In the hypovolemic state maximal renal water retention will dilute the ECF
Low volume/pressure signal over-rules osmotic signals
How can hypovolemia cause hyponatremia?
Can occur when total sodium is increased, but total water increased more
Example: congestive heart failure
CO is impaired sufficiently so adequate tissue perfusion is no longer possible
RAAS ‘thinks’ body is hypovolemic
RAAS promotes Na/water retention (volume expansion)
Volume expansion is ineffective because perturbed Starling forces (excess capillary filtration): oedema
If low volume signals activate ADH hyponatremia will ensue
