Disorders of Renal Concentration and Dilution Flashcards
What do ECF volume expansion and depletion imply about Na levels?
ECF volume depletion -> total body Na deficit. Think about it like this -> if you have a normal amount of water in the body, but sodium is relatively depleted in the ECF compartment, the water will redistribute to the ICF
ECF volume expansion -> total body Na excess
However, this does not necessarily correlate with [Na+] in extracellular fluid, which may be high or low
How is total body Na content estimated?
Based on clinical parameters on physical examination (not Na+ concentration)
Includes: skin turgor, mucous membrane moisture, edema / ascites, JVP, PCWP, etc
What parameter estimates the WATER CONTENT of extracellular and intracellular fluid compartments and how does it do this?
Plasma osmolality -> does this by assuming that except for some kidney tubules, osmolality will equilibrate across cell membranes in the body
What is osmolality in units, and what would a low osmolality imply about total body Na content and water content?
It is moles solute / kg solvent (Water)
Low osmolality -> high relative water content (compared to solutes)
Low osmolality implies a high total body water content, but it implies nothing about the ECF volume (corresponds to total body Na content, since most Na exists in ECF and pulls water towards it).
How does plasma osmolality relate to plasma Na concentration, conceptually?
Directly proportional. Thus, total body water content can be estimated by Na concentration, but ECF volume cannot be estimated by Na concentration (needs total body Na, a clinical assessment)
What is the formula for calculating plasma osmolality? Give the normal value?
2*Na + (glucose / 18) + (BUN / 2.8)
Na in mmol/L - because each Na is accompanied by an anion
Glucose in mg/dL
BUN in mg/dL
Normal value is around 290 mOsm / kg water
What is the difference between water depletion and volume depletion? What is dehydration talking about?
Water depletion - depletion of total body water (increased Na concentration / osmolality) -> dehydration refers to this
Volume depletion - depletion of ECF volume - total body Na. Dehydration should not refer to this, but sometimes sloppily applied
What are sources of total body water gain?
Drinking fluids
IV fluids which are hypoosmotic to plasma
Bladder irrigation
Enemas
What are sources of total body water loss?
Respiration, sweat (hypo-osmotic to plasma), GI tract (emesis, feces)
Renal - urine production
What are the two cases when plasma osmolality is NOT proportional to plasma [Na]?
Pseudohyponatremia:
- Artifactual hyponatremia
- Hyperosmolal hyponatremia
How does artifactual hyponatremia occur and what are two disorders responsible for this?
Since Na only dissolves in the plasma water content, and not the 7% of undissolved solids, situations where there are elevated undissolved solids can make the measured Na+ be low relative to the whole volume of plasma pulled from the lab, while the Na+ / plasma WATER is relatively normal.
Examples:
Hyperlipidemia
Hypergammaglobulinemia (i.e. multiple myeloma)
How would plasma osmolality be affected in artifactual hyponatremia?
Unaffected -> osmolality is a collagative property. Measured solutes dissolved per kg of WATER -> does not count the undissolved solids into the volume for the calculation
What is the concentration of injected normal saline and why?
154 mmol/L, since all the NaCl is dissolved in pure water.
154*0.93 = 140 mmol/L, the concentration we are used to, since 7% of plasma is normally undissolved solids
What is hyperosmolal hyponatremia and when does it occur? How can this be corrected?
In hyperglycemia due to uncontrolled diabetes mellitus, plasma osmolality truly rises because insulin is not present to bring glucose into the cells. As water exits cells into the ECF, the ECF [Na] goes down, causing pseudohyponatremia. Na cannot simply move across the membrane.
When the hyperglycemia is corrected with insulin, the [Na] will renormalize.
For a patient with a plasma glucose of 1,000 mg/dL, what is their true plasma [Na] after correction if their current [Na] is 120 mg/dL?
For every 100 mg/dL above 200 mg/dL, the plasma [Na] will go up 1.6 mM
(1,000-200)/100 = 8
8*1.6 = 12.8
12.8 + 120 = 132.8 mmol/L
Thus, this patient’s Na would still be low, and the patient would have excess TBW.
How will elevation of BUN in chronic renal failure affect plasma Na concentration?
No effect, since urea will increase plasma osmolality but not alter Na concentration because it doesn’t stay confined to one compartment (i.e. distributes equally to both compartments)
What three factors will stimulate thirst?
- Increase in plasma osmolality by 2-3%
- Decrease in blood volume
- Decreased blood pressure
What area of the brain regulates plasma osmolality? How do they relate to the BBB? how do they work? What are the osmoreceptors type?
Subfornical organ (beneath hippocampus) and organum vasculosum of lamina terminalis (OVLT)
Outside of BBB, have TRPV1 osmoreceptors and angiotensin II receptors
How will ADH release be affected by drinking?
Release will be decreased by the simple act of drinking (even before Posm decreases)
How does OVLT signal ADH secretion?
Signals thru the magnocellular neurons of the supraoptic and paraventricular nuclei of the hypothalamus. They transport ADH thru the pituitary stalk and release via neurophysin storage + release, increasing ADH secretion
Other than angiotensin II, low BP, low blood volume, and high plasma osmolality, what other factors stimulate ADH release?
Other stress-related stimuli:
Nausea
Hypoxia
Hypercapnia
Pain (nociceptors)
-> keep these all in mind as causes of normal ECV hyponatremia
Where is blood pressure sensed and how does this relate to ADH secretion?
Low pressure baroreceptors - sense stretch in response to changes of filling volume. Located in cardiac atria and pulmonary vessels
High pressure baroreceptors - aortic arch and carotid sinus, in arterial areas, sense high pressure
They relay via the 9th and 10th cranial nerves, and when they fire they inhibit ADH secretion. When they stop firing they disinhibit ADH release.
How does the sensitivity and effect size of the baroreceptors relate vs osmoreceptor control of ADH? How do they interact?
Baroreceptors - lower sensitivity (need 10% drop in blood volume to stop firing and stimulate ADH release) but more steep effect
Osmoreceptors - higher sensitivity (1% change in osmolality) but lower slope
How do the baroreceptors / osmoreceptors interact to control ADH?
The baroreceptors modify the rate of rise of ADH release based on blood volume. I.e. if blood volume is very high, a rise in plasma osmolality will not as greatly increase ADH levels
Likewise, if the blood volume is low enough, ADH secretion can be increased greatly even if plasma osmolality is low (baroreceptors have a greater effect despite lower sensitivity)
