Water Balance Flashcards
What is the normal range of plasma osmolality?
- The normal range of plasma osmolality in healthy subjects is 287±7 mOsm/kgH2O (a spread of ± 2%).
- However, this spread is mainly due to person-person variation, and in any given individual Plosm is maintained with a remarkable precision of < 0.5%.
What is the acute response to changes in cell volume due to osmolality changes? Why can’t every tissue use this acute response?
- The fine control of plasma osmolality is necessitated by the fundamental need for preserving constant cell volume.
- The main challenge to cell volume is a change in tonicity of the extracellular fluid. Therefore, all cells are equipped with volume regulatory mechanisms.
- The inherent response of a cell to osmotic swelling is the extrusion of cellular electrolytes, whereas cell shrinkage leads to the uptake of extracellular electrolytes.
- However, acute cell volume regulation in the whole body is limited to a few organs, because extrusion or uptake of electrolytes in every tissue would dramatically change the electrolyte composition of the “bath water”, i.e. the ECF.
- Since the main intracellular cation is K+, acute cell volume regulation in the whole body would result in adverse changes in extracellular [K+].
What two organs are allowed to regulate their volume in acute situations through the extrusion of electolytes? Why do each require acute response mechanisms?
- only two privileged: the intestines and the brain.
- Intestines are exposed to large sudden changes in osmolality following water intake
- the brain is enclosed in the cranium with finite space.
- Volume regulation in these organs takes place at the expense of other organs, mainly muscle, which compensate by absorbing or releasing the required K+.
Why is cell volume regulation (acute response) in the brain limited? How do brain cells adapt long-term?
- changes in excitability that result from transmembrane ion fluxes.
- brain adapts to an abnormal osmolality through small organic molecules that do not disturb cell function, such as taurine, betain, sorbitol, myo-inositol.
- “long-term” regulation takes several days to produce these small organic molecules
What other organ uses this long-term response?
the renal medulla
What is the main atom/molecule responsible for tonicity?
• osmoregulation can be equated with the regulation of plasma Na concentration.
o An abnormal [Napl] is corrected NOT by altering the amount of Na in the body, but rather by adjusting the amount of water.
o water content of the body changes much more readily than the amount of Na.
Explain how hyponatremia and hypernatremia are water problems, not salt problems.
o hyponatremia is a sign of relative water excess (overhydration) and NOT an indication of Na deficit.
• It typically arises because the kidney’s ability to excrete water is compromised.
o Similarly, high [Napl] (hypernatremia) is NOT a sign of too much Na in the body, but rather it is an indication of H2O deficit (dehydration).
o It occurs if water intake is inadequate;
When does one see inadequate water consumption clinically?
o In clinical practice it is seen in patients who cannot drink or signal thirst (infants, or people with altered mental states or disability).
o (Also seen in diarrhea and vomiting patients)
Why are clinical manifestations of hypo and hyper-natremia dominated by neurological symptoms?
• Since a change in [Napl] initiates an immediate cell volume regulatory response that alters intracellular ion concentrations, it is not surprising that the symptoms of hypo- and hypernatremia are dominated by changes in neuronal activity.
o Signs of mild dysnatremia include apathy, lethargy, nausea, vomiting and headache, while in moderate to severe cases disorientation, confusion, stupor, seizures and coma may develop.
• Besides the direct neuronal effects, the physical shrinkage and swelling of the brain can also lead to life-threatening conditions.
o Brain shrinkage, by stretching cerebral blood vessels, may cause brain hemorrhage, while hyponatremia-induced brain swelling and the resulting increase in intracranial pressure shifts structures within the skull resulting in tentorial or tonsillar herniation.
Why are changes in urine output associated with hypo- and hyper-natremia variable (i.e. poly or oligouria), depending whether the cause of the disturbance is renal or extrarenal?
• Hyponatremia is typically associated with oligouria (low urine volume), although the expected physiological response to overhydration is polyuria.
o hyponatremia kidney excretion of water is compromised, thus oligouria is the cause and not the consequence of hyponatremia.
• hypernatremia due to genuine dehydration is associated with oligouria while hypernatremia due to a renal concentrating defect is accompanied by polyuria.
In summary, why are both hypo- and hyper-natremia associated with oligouria?
• Oligouria is the cause of hyponatremia (inability to excrete water), where as oligouria is the symptom of hypernatremia (dehydration).
What is the typical amount of daily water turnover (the amount that one eat, drinks and excretes and evaporates)?
- The typical daily turnover of water in a temperate environment with a sedentary life-style is about 2.5 L.
- Roughly 1.5 L is excreted as urine, ~200 ml is lost via the GI tract and the rest is lost via evaporation from the lungs and skin (this latter component is called insensible water loss).
- To achieve water balance, we drink ~1200 ml and take up an additional ~1L water with food.
- The remaining ~300 ml is generated by metabolism.
What is the total amount of water that the kidneys can excrete everyday?
• The KD can produce up to 25 L of very dilute urine/day.
What is the maximum about of water that the KD can conserve if we are under-hydrated?
• Reduced water intake leads to the formation of less (~500 ml) but more concentrated urine, the maximum amount of water we can conserve by renal regulation is only ~1L.
Why can’t we rely on regulated skin evaporation as a source of water regulation? How much do we have to sweat in order to surpass the amount of water concentration by the kidney (in other words, what is the amount of sweat that forces us to drink water)?
- Since evaporation by sweating is critical for heat regulation, the amount of water lost via the sweat can by far exceed the amount of water that can be conserved by the kidneys.
- Thus, when evaporative water loss is >1L/d, we can remain in water balance only by increasing water intake
What are the two major water balance regulations for the overall body system?
• Maintenance of water balance requires dual regulation
o The behavioral response of thirst determines water intake
o ADH regulates renal water excretion by altering the water permeability of the collecting duct (CD).
Stimulation prompting thirst and ADH release originate from where (what organ has sensors)?
• Both responses originate from stimulation of osmoreceptors in the CNS.
Wait. If the brain monitors blood osmolality, how does the blood brain barrier factor into that? What hormones also affect the brain osmol sensors?
- Most regions of the brain are partially protected from changes in blood composition by the blood-brain barrier and by being bathed in cerebrospinal fluid whose composition is not identical to that of plasma.
- Therefore osmoreceptors are located in two areas of the brain where this barrier is “leaky”: the subfornical organ and the organum vasculosum of the lamina terminalis (OVLT).
- The lack of a barrier allows these neurons to fully sense the Na concentration of plasma, and also enables them to respond to circulating hormones such as angiotensin II and ANP.
Explain the difference between the thirst and ADH sensors in the brain. Why does it make sense that the threshold for ADH is lower than the threshold for thirst? (long version here, summary as next question).
- The osmoreceptors that regulate thirst and ADH release are located in separate regions of the brain and have different sensitivities to changes in tonicity.
- The threshold for ADH secretion is lower than what triggers thirst, and therefore under normal conditions water balance is maintained by regulating ADH secretion and thus water excretion.
- The thirst mechanism operates at a slightly higher tonicity. As mentioned above, with excessive water loss such as during exercise, fever or in a hot climate, the kidneys’ ability to conserve water becomes exhausted, and the maintenance of H2O balance depends almost exclusively on the thirst mechanism.
- The body also needs to protect itself against rapid changes in osmolality that might result from excessive water intake. Since the rate at which we can consume water greatly exceeds the rate at which water can be absorbed, regulating water intake solely by osmoreceptors is insufficient, since by the time plasma osmolality declines, more water had entered the GI tract than necessary to correct the deficit. This is undesirable since a potential overshoot is dangerous.
In Summary, why the different thresholds of ADH vs Thirst Receptors in the brain?
- ADH can regulate faster and more accurately. Thirst is only needed when the KD have exceeded their water retention maximum (1L).
- If thirst were the lower threshold, it would have lower accuracy because we can drink more water than needed… because it take time to absorb the water through the intestines.
What sensors have we developed to mitigate the danger of over drinking?
- cold receptors in the mouth
- stretch receptors in the esophagus and stomach.
- Activation of these receptors temporally inhibits the sensation of thirst and thereby prevents over-hydration.
Normally, maintaining osmolality is the priority, but in the case of extreme hypovolemia or hemorrhagic shock what happens?
- Under normal conditions the regulation of cell volume takes precedence over the regulation of ECFV. However, with extreme disturbances of ECFV, like in hypovolemic or hemorrhagic shock, the body changes priorities, and is willing to tolerate changes in plasma osmolality as a price of preventing circulatory collapse.
- This volumetric control of ADH and thirst is mediated by signals arriving to the osmoreceptors from cardiovascular control centers.
