Extracellular Volume and Osmoregulation Flashcards
When sodium AND water are both ingested d in a concentration similar to plasma water. . .
. . . there is NO CHANGE in osmolality.
Water balance is unaffected, though volume status will increase. This excess sodium and water (i.e., volume) can promptly be excreted by the kidneys unless there is a stimulus to retain salt and water.
Why is sodium multiplied by 2 in the osmolarity equation?
To represent chloride! (and any other negative ion, but basically chloride)
Pseudohyponatremia
Measurement of hyponatremia resulting from a laboratory artifact. Measuring the serum osmolality can assess this. Normally, the serum osmolality changes in parallel with the serum sodium concentration
The same volume of diluent is always used; the degree of dilution is estimated under the assumption that the serum contains 7% solid-phase particles. When the fraction of solid-phase particles is larger (because of very high levels of triglycerides, cholesterol or plasma proteins), the same amount of diluent results in a greater dilution.
Hormonal changes associated with increasing sodium intake
Fluids excreted from our bodies (sweat, vomit or gastrointestinal secretions) are . . .
. . . either hypoosmotic or isoosmotic
Chronicity in treatment of hyponatremia
Any time period longer than 24 hours is considered “chronic”. This is because there has been time for adaptation.
The rapid correction of hyponatremia can result of rapid changes in neuronal cell size which can cause permanent neurologic damage. As such, the correction of asymptomatic chronic hyponatremia should be slow and monitored closely.
Increased extracellular fluid will increase ___
Increased extracellular fluid will increase both the volume of the plasma and the interstitial fluid (this can result in high blood pressure and edema)
Fundamentally, vasopressin promotes _____ water reabsorption, and so ____.
Fundamentally, vasopressin promotes isotonic water reabsorption, and so cannot influence osmolarity of serum.
Hyperosmolar hyponatremia
This occurs when there is an “effective osmole” which is contributing to the total serum osmolality and this has led to movement of water from the cells into the extracellular space. The most common cause of this phenomenon is hyperglycemia from insufficient insulin or insulin resistance.
When this is caused by hyperglycemia, once the hyperglycemia is corrected, water will return to the cells and the serum sodium will rise.
One of the most common causes of nephrogenic DI
Lithium! Even normal levels of lithium may be responsible in some individuals.
Lithium enters the principal cells via the ENaC and accumulates in the cells. Several mechanisms may be at work including decreased expression of the ADH receptor and decreased transport of the aquaporins from the cytosol to the luminal membrane of the collecting duct.
Evaluation of polyuria
- What is in the urine?: If it is very dilute, then the polyuria represents a water diuresis. If there a large amount of solute, then it is considered a solute diuresis.
- Is the diuresis appropriate?: A water diuresis may occur when an individual drinks a large amount of water. This also may occur if a patient is ADH deficient (diabetes insipidus). A solute diuresis may represent diabetes mellitus.
Summary of osmotically active hormones
Sodium gain (with water) leads to ___
edema and hypertension
Sodium loss (with water) results in ___
volume depletion and hypotension
Hyponatremia cannot occur from ___.
Hyponatremia cannot occur from sodium loss, only water gain.
Osmolality is measured in the laboratory by ___
Osmolality is measured in the laboratory by freezing point depression
More on ADH
Polypeptide that is synthesized in the supraoptic and paraventricular nuclei in the hypothalamus.
Rapidly metabolized in both the liver and kidney with a half-life of only 15-20 min. Vasopressin binds to V1 receptors on the vasculature to cause vasoconstriction and to the V2 receptors on the basolateral side of the collecting duct in the kidney. V2 binding activates adenylyl cyclase, and downstream AQP2 insertion.
ADH alone will not correct ___
ADH alone will not correct hypernatremia
It will only limit further losses of water. This is because water is reabsorbed with an isotonic level of sodium. In order to restore normal osmolality, consumption of water or other dilute fluids is required.
Similarly, if an individual has hyponatremia in the presence of ongoing ADH release, their serum sodium level will not continue to decline if there is no additional dilute fluid intake.
Intracellular fluid compartment
~2/3 total body fluid
For chronically hyponatremic patients, sodium level should be increased by no more than . . .
. . . 6-8 mEq/L
When water is ingested without sodium . . .
. . . the water will distribute in all compartments. The serum sodium (and serum osmolality) will decrease.
This will lead to an increase in cell size through water movement INTO all cells until the osmolality is the same in both the ECF and ICF. If the individual is not volume depleted, there is no stimulus for ADH. ADH has a short half-life so the individual will promptly excrete this water load as dilute urine and the serum osmolality will return towards normal.
Stimuli of thirst
- Hyper-osmolality
- Hypotension
- Hemorrhage
Plasma osmolarity equation
Calculated plasma Osm = 2 x SNa+ + glucose/18 + BUN/2.8
Aldosterone mechanism
Aldosterone increases sodium reabsorption via the epithelial Na+ channel (ENaC) in the cortical collecting duct.
Aldosterone also plays a role in acid-base homeostasis and potassium (K+ ) balance.
Even if the kidney is acting as strictly as it can to preserve water, some will still be lost. Where is this lost to?
- The volume of water absolutely necessary for waste excretion
- Sweat
- Breathing
Effective osmolarity
This term refers to whether the introduction of a particular substance to a fluid will induce a change in osmolality of that fluid and a change in cell size (i.e. tonicity). This does not always occur because some substances may move and equalize between compartments.
For example, urea moves freely between the intracellular and extracellular spaces and is therefore an “ineffective” osmole (exept in the kidney)
Evaluation of polyuria
ADH in response to osmolality change and volume change
Cellular response to acute hyper- and hypo-osmolar stresses
Assessing ADH
Note that the right option represents SIADH
Causes of SIADH (expanded list)
Not on here explicitly, but don’t forget TB!
Bodily osmolality sensor
The body only needs one osmolality sensor, as osmolality is the same throughout the body. Osmoreceptor functions of the OVLT (organum vasculosum laminae terminalis) nuclei and supraoptic nuceli control thirst and vasopressin release, respectively.
In response to hyperosmolar-induced cell shrinkage, specialized mechanical-stretch TRPV cation channels are activated, allowing the influx of positive charges and consequent cell depolarization. The convserse is also true.
So, the body uses cell size as an approximation of osmolality.
Types of fluid we can infuse
Vasopressin secretion is not very sensitive to ___, but is extremely sensitive to ___.
Vasopressin secretion is not very sensitive to changes in blood pressure, but is extremely sensitive to changes in plasma osmolarity.
Additionally, on the receptor level, V2 receptors on the collecting duct are saturated at much lower concentrations of aldosterone than V1 receptors on the vascular smooth muscle.
Causes of SIADH
