2. Physiology
• Sodium is the major extracellular cation- 135-
145mmol/lt.
• The total body sodium content of 70kg male
subject is of 4000 mmol.
• 50% of total body sodium content exists in the
extracellular compartment.
• 40-45% is found in bone, skin and cartilage.
• 5-10% occurring intracellularly.
• The average dietary sodium intake - 150 mmol.
3. INTERSTITIAL vs PLASMA SODIUM
• The extracellular space is subdivided into the
intravascular compartment and the interstitial
compartment.
• Water moves freely across both the
compartment.
• The ionic composition of two compartments is
not identical, because of (a) a difference in
protein concentration (b) the Gibbs-Donnan
effect.
4. Contd.
• Exchangeable sodium- 70% of total sodium,
both intra and extra cellular and part of bone
sodium.
• Non exchangeable sodium- bone, cartilage
and skin.
• The sodium concentration of cartilage is
nearly twice that of plasma.
• Proteoglycans in skin,bone serve as a sodium
reservoir.
7. • High salt diet accumulation of Na in skin
interstitium activation of tonicity
responsive enhancer binding protein (TonEBP)
in mononuclear phagocyte system (MPS) cells
vascular endothelial growth factor-C
secretion by macrophages increased
endothelial nitric oxide synthase (eNOS)
expression.
• Inhibition of these , increases blood pressure.
8. RENAL REGULATION OF SODIUM
EXCRETION
• Each day, the glomeruli filter roughly 25,000
mEq of Na.
• Kidneys typically absorb over 99%.
• Rates of Na reabsorption are greatest in the
proximal tubule.
• The ability to alter Na transport in the proximal
tubule is limited, and highest in collecting duct.
9. Overview of Na+ Reabsorption along the Nephron
65% of filtered Na+ is reabsorbed
from the proximal tubule.
25% of filtered Na+ is reabsorbed
from the thick ascending limb.
5% of filtered Na+ is reabsorbed
from the distal tubule.
4-5% of filtered Na+ is reabsorbed
from the collecting duct.
17. Tubuloglomerular feedback
• Changes in tubular fluid Na+ inversely affect
GFR.
• Uptake of salt by NKCC2 ATP release
broken down to adenosine afferent
arteriolar constriction.
18. Peritubular capillary starling forces
•Rate is the absolute rate of reabsorption.
•Kr is the capillary reabsorption coefficient.
•πc and Pc are the local capillary oncotic and
hydraulic pressures, and πi and Pi are the
corresponding interstitial pressures.
19. Pressure natriuresis
• Renal Na+ and water
excretion are increased
when renal arterial
pressure increases
without change in GFR
• Mechanism is intra-
renal and does not
require neural or
endocrine input
21. Aldosterone
• Alters renal Na+ reabsorption in response
to dietary fluctuations
• Main stimuli for release: Angiotensin II,
hyperkalemia, ACTH
• Main effect: Increases number of open
luminal Na+ channels and activity and
number of basolateral Na+-K+ ATPase
pumps in principal cells of collecting ducts
22. Angiotensin II
• Efferent > afferent arteriolar
constriction (increased FF) results in
changes in peritubular Starling forces
that facilitate Na+ reabsorption
• Direct stimulation of Na+-H+ antiporter
in proximal tubules
• Stimulates aldosterone secretion from
adrenal glands
35. GENERAL GUIDELINES
• Na deficit = 0.6 x wt(kg) x (desired [Na] - actual [Na])
• When do we need to Rx quickly?
– Acute (<24h) severe (< 120 mEq/L) Hyponatremia
• Prevent brain swelling or Rx brain swelling
– Symptomatic Hyponatremia (Seizures, coma, etc.)
• Alleviate symptoms
• Initially treat“Quickly”: 3% NS, 1 mEq/kg/h until:
• Symptoms stop
• 3-4h elapsed and/or Serum Na has reached 120 mEq/L
• Then 0.5 mEq/L/h with 0.9% NS or simply fluid restriction.
• Aim for overall 24h correction to be < 10-12 mEq/L/d to prevent myelinolysis
37. • Calculating volume of infusate
Volume of infusate = {1000 mL x (Change in[Na+])goal}/(Change in
[Na+])
• Calculating rate of infusion
Rate of infusion = volume of infusate/hours of infusion
• Patient’s weightX desired correction rate(mEq/L/hr)= infusion rate
of 3% NaCl(ml/hr)
38. Chronic asymtomatic hyponatremia
• Stop non-essential fluids, medications.
• Cause-specific treatment.
• Fluid restriction.
• In moderate hyponatraemia- increase in serum
sodium >10 mmol/L during the first 24 h and >8
mmol/L during every 24 h thereafter.
39. SIADH
• Severe hyponatremia with hypertonic saline.
• Fluid restriction- 0.5- 1 Lt per day.
• Demeclocycline
• Urea
• Vaptans
41. VAPTANS
• Vasopressin receptor antagonists.
• Use in euvolemic/hypervolemic hyponatremia.
• Not suitable for hyponatremia due to cerebral
salt wasting and psychogenic polydipsia.
• Approved for patient with serum Na
<125mEq/L or >125mEq/L with symptoms of
hyponatremia and resistant to fluid restriction.
42. • Avoided in pregnant women.
• Aquaresis delayed 1-2 h.
• Promotes slow aquaresis.
• Not useful if Sr Cr is >2.5mg/dl.
• Adverse Effects: -
– Thirst 8-16%; dry mouth 4-13%
– Hypernatremia in 5%
53. •Point prevalence of hyponatremia was 13.5% and of hypernatremia was 2%.
•During follow-up of ~5 years, 26% patients developed at least one episode of
hyponatremia and 7% had hypernatremia
