RENAL: Salt & Water Balance Flashcards
Define osmoregulation
Regulation amount of water in body to maintain constant ECF osmolarity
Define volume regulation
Regulation of blood volume and pressure to ensure effective circulating volume
Accomplished by regulating total amount (not concentration) of Na in ECF
Describe the role of RAAS in regulating blood volume
RAAS activated by:
- Reduced renal perfusion
- Increased sympathetic activity
Both are interpreted as a fall in blood volume
Aldosterone secretion is increased by:
- RAAS
- Increased plasma (K+)
Describe the effect of aldosterone in volume regulation
Acts on principal cells lining CD:
- Increases Na/K ATPase
- Increases expression of ENaC channels on luminal membrane
Results in:
- Increased Na+ reabsorption
- Increased K+ secretion
Acts on intercalated cells of CD:
- Increases H+ ATPase
Results in:
- Increased H+ secretion
- Increased HCO3- reabsorption
What mechanism is the principal volume regulation system?
RAAS!
RAAS:
- Normal, continuous adjustment of Na excretion and ECF volume
- Can reduce Na excretion tov ery low levels in hypovolemia
ADH:
- Last line of defence against volume depletion
- ADH primary regulator of osmoregulation, so if osmolarity is too large or too small, ADH is the primary response
- Non-osmotic ADH secretion if BP drops by 10-15% - This means ADH secretion has been increased by low BP, and not due to osmoregulation purposes. This is to further increase blood volume
- RAAS is already fully activated
Discuss the role of osmotic forces in determining the distribution of water
Add pure water ECF:
- Water distributes both ECF and ICF
- ECF and ICF both expanded
- Dilution of ECF results in osmotic gradient from ECF to ICF, which distributes water across both compartments until osmotic eqm restored
- Changes in osmolarity of ECF result in shifts of water b/w ECF and ICF, hence blood volume changes
How is osmolarity of the ECF adjusted?
- Add/remove water
This means that too little water (dehydration) will show as an increase in ECF osmolarity and too much water (overhydration) will show as a decrease.
Describe the role of sodium in ECF volume
Total amount of sodium in ECF determines ECF volume
For example, if isotonic solution (equal amounts salt + water) added to ECF, salt + water is retained in ECF as the cell membrane is impermeable to salts. Therefore, there’s no change is osmotic gradient, so the volume of this compartment expands only. Starling forces will then ensure the distribution of the volume b/w plasma and interstitial compartments, increasing the effective circulating volume.
How is blood volume linked to blood pressure?
- Increase ECF = Increase blood volume
- Increase venous return (Starling forces)
- Increased filling
- Increased CO (Starling’s law)
- Increase BP
MABP = CO x TPR
How is ECF volume sensed?
- Atrial stretch receptors, baroreceptors, afferent arteriole, NaCl delivery to DT
- This triggers RAAS or ANP (have opposing effects)
- Change in renal sodium and water excretion
- Change in ECF volume
This is a loop
How is renal Na excretion controlled?
Most filtered salt + water reabsorbed in PT - this fraction increases with RAAS
Much smaller, variable fraction reabsorbed from DT and CD
- Reabsorption of Na and solute-free water are separated
- Aldosterone-mediated Na reabsorption increases plasma osmolarity, which is then adjusted by pure water reabsorption via ADH system
- Result is increased Na and water in ECF with little or no change in plasma [Na] or osmolarity
Describe renal tubule mechanisms of osmoregulation
Ability to vary amount of solute-free water in urine:
- Concentration of interstitial fluid in medulla
- Dilution of urine in ascending limb and distal tubule
Urine concentration (hence H2O excretion) can be varied b/w these limits
Describe the action of ADH
Urine entering collecting duct is maximally dilute. Osmotic gradient for water reabsorption is large, but in absence ADH, CD impermeable to water
Low levels ADH - Some water reabsorbed
Maximal ADH levels - Limit of water reabsorption is set by osmolality osmolality of medullary interstitial fluid, this is max urine concentration (hence minimum water excretion)
ADH:
- Changes detected osmoreceptors in anterior hypothalamus
- Project to magnocellular neurones of paraventricular and supraoptic nuclei of hypothalamus
- PVN and SON neurones release ADH from their axon terminals in posterior pituitary
- ADH binds to V2 receptors on basolateral membrane, this forms new aquaporins but also opens existing aqauporins on apical membrane, which allows water to move into cells and out of CD via osmosis through basolateral into interstitial fluid, and then into blood
- 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. This is an additional, non-osmoregulatory role for ADH when severe drop in BP.
Net water loss increases in plasma (ECF) first detected, ADH increases to counteract. Opp when when water in excess
Describe how thirst impacts osmolality maintenance
- Normal range 285-295 mOsm/kg
- Changes detected by osmoreceptors in anterior hypothalamus
- Projects to centres mediating thirst/drinking
- Strong desire to drink when plasma osmolality ≥295 mOsm/kg
- Oropharyngeal and upper GI receptors reduce thirst on drinking
- Thirst is also stimulated by
- Large (10-15%) drops in blood volume/pressure
- Angiotensin 2 acting on hypothalamus
What is the main determinant of ECF osmolality?
- Na+ - Main cation ECF
- Principle of electroneutrality dictates that molar equivalent anions must be present
- Mainly Cl-, significant amount HCO3-, small contribution from other inorganic + organic anions
- Contribution of Na+ to ECF osmolality is 2x plasma [Na+]
- Plasma osmolarity in mOsm L-1 can be estimated from:
- 2[Na+] + 2[K+] + [glucose] + [urea]
How do disturbances of water balances present as disturbances of plasma [Na]+?
Water deficit:
- ECF osmolality increases (hyperosmolality)
- Hypernatremia (Na >145)
Water excess:
- ECF osmolality decreases (hypoosmolality)
- Hyponatremia (Na <135)
Describe hypernatremia and its causes
Too little water, leading to increase in Na concentration
- Hypernatremia (Na > 145) always means hyperosmolality of ECF
Causes can be:
- Gain of sodium (though this is rare)
- Loss of water (much more common)
- Extra-renal losses
- Dehydration
- Infection (increased losses via skin and lungs)
- Renal losses
- Osmotic diuresis (occurs when fluid in distal tubule is insufficiently diluted, reducing gradient for water reabsorption)
- Diabetes insipidus:
- Renal water loss (inability to concentrate urine)
- Lack of effective ADH, either - Central (failure of secretion), nephrogenic (lack of renal response). Presents with polydipsia and polyuria. Thirst mechanism alone normally enough to prevent significant hypernatermia, but will rapidly develop if access to water restricted
- Extra-renal losses
Describe hyponatremia and its causes
Water excess, associated with hypoosmolality - This is true hyponatremia
‘Pseudo’ hypontremia occurs when some other solute is present in sufficient quantity that the proportional contribution of sodium to plasma osmolality is reduced
Continued ingestion of water w/o reducing ADH secretion will always lead to hyponatremia
Syndrome of inappropriate ADH secretion (SIADH)
- Hyponatremia
- High urine osmolarity
Many causes, e.g.,
- CNS damage/disease
- Ectopic ADH production by tumour
Discuss hyponatremia and ADH
Under normal conditions, function ADH = osmoregulation
However, large drop in BP can stimulate ADH release
In hypovolemic state, maximal renal water retention will dilute the ECF
Discuss hyponatermia and hypervolemia
Can occur when total Na increased, but total water increased more:
- Example, congestive heart failure:
- RAAS - Body thinks it’s hypovolemic
- Na/water retention (volume expansion)
- Volume expansion ineffective bcs perturbed Starling forces (excess capillary filtration) - oedema
- If low volume signals activate, ADH hyponatremia will ensue
If ADH is secreted in the absence of increased osmolarity then dilution of the body fluids will be the result
How does hypernatraemia causes drowsiness and confusion?
- Neuronal cells will lose water and shrink due to hyperosmolarity
What screening value shows activation of RAAS?
Urine sodium levels - RAAS increases Na reabsorption, which will mean Na isn’t being excreted, so levels are low if RAAS is activated
What screening value shows activation of ADH as the primary response?
Urine osmolality - When ADH is in maximal response, urine osmolality will be very high, as the urine will be very concentrated as H2O has been reabsorbed
