What happens to total body water following Na+ infusion?
It shifts (water moves from the ICF to the ECF)
What happens to compartmental water balance following infusion of pure water?
The water redistributes equally to both ICF and ECF (water is freely permeant across membranes)
Why is it important to maintain a relatively constant serum osmolarity?
The brain cannot tolerate small changes in osmolarity (it will swell or shrink)
Consequences of brain shrinkage
Pulls apart from meninges → hemorrhage, meningeal tears, neuronal/glial tears
Consequences of brain swelling
Herniation beyond the tentorium → compression of the brainstem
Why can the brain tolerate minor changes in serum osmolarity?
Blood-brain barrier
Most dysnatremias are [mild, moderate, or severe] and SNa is in the range [#]-[#] mM
Mild; 125-155 nM
What kinds of patients most often have dysnatremias?
Hospitalized, institutionalized, or “polypharmacied” patients
T/F: Dysnatremias are often emergencies and require aggressive treatment
False – most are non-emergent and require only a “tweak” in treatment
Define osmoregulation
Maintenance of constant Sosm (serum osmolarity)
What areas of the brain sense changes in Sosm?
Supraoptic nucleus (SON)
Hypothalamic thirst nucleus
Hypothalamic cells can sense Sosm
changes of [%] once the level is about [#] mOsm
1%; 285-290 mOsm
How do these nuclei respond to increased Sosm? SON Hypothalamic thirst nucleus
ADH secretion
Increase thirst drive
How do stimuli from the baroreceptor and brainstem nuclei affect ADH release?
Lower the threshold for ADH release
Stimuli that can lower the threshold for ADH release from the SON
Decreased PO2
Decreased BP
Decreased ECFV
Pain/stress
Nausea
Drugs
ADH is released from the [anterior or posterior] pituitary
Posterior
Operational definition of euvolemia
Intravascular volume required to maintain the least preload for optimizing stroke volume
How is preload measured?
Swan-Ganz catheter
Practical definition of euvolemia
Intravascular volume that maintains stable BP and HR (lying or standing), without peripheral pitting edema or pulmonary vascular congestion
Diuretics lead to which one? A. Too much water for the amount of salt B. Too little salt for the amount of water C. Too much salt and water, but more water than salt
B. Too little salt for the amount of water
Cirrhosis leads to which one? A. Too much water for the amount of salt B. Too little salt for the amount of water C. Too much salt and water, but more water than salt
C. Too much salt and water, but more water than salt
Molecular mechanism for SON response, leading to decreased ADH release
Decreased Sosm → SON cell swelling → closure of stretch-inactivated cation channels → less depolarization → fewer APs → decreased Ca2+ entry at terminal → decreased ADH release
Molecular mechanism for decreased ADH resulting in decreased urine osmolarity
Decreased ADH binding at V2 receptors in collecting duct → less exocytosis of aquaporins into apical membrane → decreased water permeability → decreased urine osmolarity (urine is more dilute)
Increased renal free water clearance → [increase or decrease] in Sosm
Increase
4 major causes of hyponatremia
Stimulus for inappropriate thirst
Stimulus for massive ADH release
Salt wasting with water replacement
Overactivation of CVMP
Osmolarity of the most dilute urine possible
50 mOsm/L
ADH release is inappropriate if Sosm falls below [#]
280 mOsm
CVMP is a [non-osmolar or osmolar] drive for ADH secretion
Non-osmolar
Methods for determining a patient’s volume status
Weight
Recent photograph
Orthostatic BP changes
Central venous pressure
How can cancer cause hyponatremia?
Paraneoplastic secretion of an ADH-like substance
How can CNS inflammation or injury cause hyponatremia?
Cytokine stimulation of SON neurons → ADH release
How can affective disorders cause hyponatremia?
Psychotic thirst
Antidepressants → non-osmotic induction of ADH release
The urine of a hyponatremic patient should be below [#] mOsm
100 mOsm
How can you measure renal function?
Serum creatinine
The urine of a hyponatremic patient should have UNa below [#] mEq/L
20 mEq/L
A hyponatremic patient should be hyper-osmolar, with Sosm < [#] mOsm
