1. The following is material that is not all Dr
The following is material that is not all Dr. Ciorciari's original thoughts and not fully referenced to give credit to all information cited. Further this is not considered an authoritative source but suggestions and perspectives that may aid in guiding your art of medicine

2. Sodium Disorders: Hyponatremia
William Harper, MD, FRCPC
Endocrinology & Metabolism
Assistant Professor of Medicine
McMaster University

4. Normal Serum [Na] (135-145 mEq/L) Closely Guarded
ADH
(pM)
↓ ECFv
Thirst 5
130
135
140
145
PNa (mEq/L)

5. What is Appropriate Urine Concentration?
Complete DI
Defective osmoreceptor, normal AVP release to ECFv contraction
High-set osmoreceptor: AVP release is sluggish/delayed
AVP release at normal Posm but subnormal in amount

6. Osmolality Plasma Osmolality: Posm = 2 (Na) + glucose + urea
Normal = 2 (140) = 290 ( mM)
Urine Osmolality:
Normal: mM
Maximal dilution mM (USG )
Maximal concentration mM (USG )
Concentrated Urine: > 500 mM (at least!), USG > 1.017
i.e. UOSM > POSM is not enough to R/O Diabetes Insipidus

7. Urine Specific Gravity USG
Estimates solute concentration of urine on basis of weight as compared with an equal volume of distilled water
Normal Posm is % heavier than water so PSG =
Each ↑ in UOSM mM ↑ USG by 0.1% (0.001)
Therefore, USG of ~ UOSM mM
Larger MW urinary OSM (glucose, radiocontrast, carbenicillin) if present will falsely elevate USG
Nothing falsely lowers USG

8. Hyponatremia Serum OSM Low Normal High *Note: all have ↑ADH ECFv * Low
Marked hyperlipidemia
(lipemia, TG >35mM)
Hyperproteinemia
(Multiple myeloma)
Hyperglycemia
Mannitol
Hypotonic
Hyponatremia
*Note: all have ↑ADH
SIADH: inappropriate
Rest: appropriate
ECFv *
Low
High
Normal
CHF
Cirrhosis
Nephrosis
Hypothyroidism AI
SIADH
Reset Osmostat
Water Intoxication
1° Polydipsia
TURP post-op
Renal loss (UNa > 20)
Diuretics
Thiazide
K-sparing
ACE-I, ARB
IV RTA, Hypoaldo
Cerebral salt wasting
Extra-renal loss (UNa <10)
Bleeding
Burns
GI (N/V, diarrhea)
Pancreatitis

9. Rx Hyponatremia When do you need to Rx quickly?
Na deficit = 0.6 x wt(kg) x (desired [Na] - actual [Na])
(mmol)
When do you 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
“Quickly”: 3% NS, 1-2 mEq/L/h until:
Symptoms stop
3-4h elapsed and/or Serum Na has reached 120 mEq/L
Then SLOW down correction to 0.5 mEq/L/h with 0.9% NS or simply fluid restriction. Aim for overall 24h correction to be < mEq/L/d to prevent myelinolysis

10. Rx Hyponatremia (Example)
Na deficit (mmol) = 0.6 x wt(kg) x (desired [Na] - actual [Na])
60 kg women, serum Na 107, seizure recalcitrant to benzodiazepines.
Na defecit = 0.6 x (60) x (120 – 107) = 468 mEq
Want to correct at rate 1.5 mEq/L/h: 13/1.5 = 8.7h
468 mEq / 8.7h = 54 mEq/h
3% NaCl has 513 mEq/L of Na
54 mEq/h = x
513 mEq L
x = rate of 3% NaCl = 105 cc/h over 8.7h to correct serum Na to 120 mEq/h
Note: Calculations are always at best estimates, and anyone getting hyponatremia corrected by IV saline (0.9% or 3%) needs frequent serum electrolyte monitoring (q1h if on 3% NS).

11. Rx Hyponatremia Rx slowly (correct < 0.5 mEq/L/h, 10-12 mEq/L/d)
Symptomatic/Acute: rapid Rx has resolved symptoms and brought serum Na up to 120 mEq/L
Asymptomatic, mild, chronic hyponatremia
Want to prevent myelinolysis
Increased risk: Women, alcoholics, malnourished
ECFv contracted
Bolus NS until BP, HR, JVP stable
Then correct slowly with 0.9% NS or po salt
ECFv Normal or ECFv Overloaded
Fluid Restriction alone (exception: SAH, HI, post-neurosurgery)
i.e. they do NOT need any IV or po salt!

12. SIADH Ddx Intracranial disease Pulmonary disease
Chest wall disorder (surgery, VZV)
Severe pain or emotional distress
Severe N/V
Ectopic ADH: Small cell lung cancer
Drugs: opiods, carbamazepine, chlorpropamide, cyclophosphamide, cisplatin, vincristine, vinblastine, amitriptylline, SSRI, neuroleptics, bromocriptine, ecstasy (MDMA)

13. SIADH Diagnosis Treatment Normal ECFv (or slightly increased)
Hypothyroidism & AI ruled out
↓ serum Na/OSM
UOSM > 100 mM, UNa > 40 mEq/L
Low plasma uric acid (< 238 umol/L) (1 mg/dL=59.48 µmol/L)
Treatment
Fluid Restriction
Oral Salt, Hi-protein diet or Urea (30 g/d): promote solute diuresis
Lasix 20 mg po od-bid: Loop direct diminishes medullary gradient
Demeclocycline mg bid (can be nephrotoxic)
Lithium (induces NDI)
IV salt solution:
Rarely if ever needed (i.e. only if symptomatic with SZ/coma)
Solution given must be of greater OSM than UOSM or in long run will just make hyponatremia worse (often IV NS not sufficient)

15. SIADH: Example UOSM fixed 600 mM due to ADH action
1L NS given: 300 mM (154 mM each of Na and Cl)
All sodium will be excreted as renal sodium handling is intact in SIADH.
300 mmoles of osmols given excreted in 500cc urine (300mmoles/500mL = 600 mM)
Therefore net gain of 500 cc free water!
1L 3% saline given: 1026 mmoles
Excreted in 1.7L to keep UOSM 600 mM
Therefore net loss of 700 cc free water!
NOT advocating use of any IV NS (0.9% or 3%) in SIADH unless absolutely neccesary (i.e. SZ, coma). Most SIADH hyponatremia is chronic and should be corrected slowly with fluid restriction ONLY.

16. Reset Osmostat 25-30% of circumstances which cause SIADH
Downward resetting of the threshold for both ADH release and thirst.
Mild asymptomatic hyponatremia (Na mEq/L)
Distinguish from SIADH by observing response to water load (10-15 mL/kg po or IV)
Normal subjects and those with reset osmostat will secrete the entire water load over 4h without any worsening of the hyponatremia
Attempts to correct hyponatremia in reset osmostat are not needed and will cause severe thirst

17. Cerebral Salt Wasting Cerebral disease (particularly SAH)
Mimics SIADH with hyponatremia except primary defect is salt wasting not water retention.
Circulating factor which impairs renal tubular fn.
Atrial natriuretic peptide?
Brain natriuretic peptide?
Endogenous ouabain?
Plasma urate variable (normal or even lower than SIADH)
Treatment is NS to correct ECFv contraction

18. SIADH v.s. Cerebral Salt Wasting
CSW
Serum Na ↓
ECFv
Normal
UNa ↑ ↑↑
UOSM
Urine volume
N or ↓
Serum urate
Urine urate
N or ↑

19. Rx Hyponatremia: acute SAH/Head injury
May have SIADH, CSW or Both!
Often difficult to tell which
Fluid restriction inappropriate for CSW as may exacerbate ECFv contraction and precipitate cerebral vasospasm and subsequent cerebral infarction
IV NS inappropriate for SIADH if UOSM > 300 mM (will make hyponatremia worse)
Rx with IV NS:
Start with 0.9% NS (as per hypervolemic therapy to prevent cerebral vasospasm)
If hyponatremia worsens on 0.9% NS (due to an SIADH component to hyponatremia) consider switch to 3% NS
Goal: 0.5 mEq/L/h (only if symptomatic 1-2 mEq/L/h)
Fludrocortisone
mg/d
May also be beneficial in recalcitrant cases to alleviate CSW.

20. Indications for 3% NaCl Symptomatic hyponatremia (SZ, coma)
Acute severe hyponatremia (<24h, < 120 mEq/L)
SAH with hyponatremia worsening on 0.9% NaCl

21. Sodium Disorders Hypernatremia
William Harper, MD, FRCPC
Endocrinology & Metabolism
Assistant Professor of Medicine
McMaster University

22. GI losses: Secretory diarrhea (cholera, VIPOMA, etc) don’t get hypernatremic as diarrheal fluid is isotonic to plasma, but the more common diarrheas due to viral/bacterial infections or osmotic diarrhea is hypotonic to plasma and therefore does cause hypernatremia
Mineralcorticoid excess syndrome: they have persistent mild volume expansion which resets the osmostat regulating antidiuretic hormone release and thirst upward by several mEq/L. As a result, patients with primary aldosteronism usually have a stable plasma sodium concentration between 143 and 147 mEq/L.

23. Diabetes Insipidus Ddx Polyuria: > 3 L/d + Polydipsia: > 3.5 L/d
Diabetes Mellitus
Hypercalcemia
Solute diuresis:
Volume expansion 2° saline loading
High-protein feeds (urea as osmotic agent)
Post-obstructive diuresis
Diabetes Insipidus:
Central (CDI)
Nephrogenic (NDI)
Primary (Psychogenic) Polydipsia

24. Diabetes Insipidus Ddx
Central (CDI)
Idiopathic
autoimmune
Neurosurgery, head trauma
Cerebral hypoperfusion
Tumor
Craniopharyngioma, pituitary adenoma, suprasellar meningioma, pineal gland, metastasis
Infiltration
Fe, Sarcoid, Histiocytosis X
Nephrogenic (NDI)
X-linked recessive
Hypokalemia
Hypercalcemia (2° to HPT in particular)
Renal disease: after ATN, postobstructive uropathy, RAS, renal transplant, amyloid, Sickle cell anemia
Sjogren’s
Drugs:
Lithium, 20% of chronic users
Demeclocycline, amphotericin, colchicine

25. What is Appropriate Urine Concentration?
Complete DI
Defective osmoreceptor, normal AVP release to ECFv contraction
High-set osmoreceptor: AVP release is sluggish/delayed
AVP release at normal Posm but subnormal in amount

26. Intact thirst & access to water
Diabetes Insipidus
Intact thirst & access to water
Hi-normal serum sodium ( mEq/L)
Polydipsia (crave cold fluids)
Polyuria, Nocturia  sleep disturbance
1° treatment is pharmacological
Impaired thirst or access to water:
Hypernatremia
Insufficiently concentrated urine
1° treatment is free water (enteral or IV D5W)

27. Diabetes Insipidus Healthy out-patients
DI with Intact thirst or access to water
Hi-normal serum sodium ( mEq/L)
Polydipsia (crave cold fluids)
Polyuria, Nocturia  sleep disturbance
1˚ Psychogenic Polydipsia
Low-normal serum sodium ( mEq/L)
Anxious middle-aged women
Psychiatric illness, phenothiazine (dry mouth)

28. 1˚ Polydipsia

29. 1˚ Polydipsia: “What came first?”
The Polyuria or the Polydipsia?
The Chicken or the Egg? (Egg)

30. Water Deprivation Test
Hold water intake for 2-3h prior to coming in.
Continue to hold water & Monitor:
Urine volume, UOSM q1h
Serum Na, OSM q2h
If serum OSM/sodium do not rise above normal ranges & UOSM reaches 600  1˚ Polydipsia
If serum OSM reaches mM & UOSM doesn’t ↑
Diabetes Insipidus established
Endogenous ADH should be maximal, check serum ADH
2 green rubber stopper tubes, pre-chilled, on ice, need biochemist
Give DDAVP 10 ug IN
CDI: UOSM ↑ by % (complete CDI), ↑ by 15-50% (partial CDI) with absolute UOSM > 345mM
NDI: UOSM ↑ by up to < 9%, sometimes ↑ as high as 45% but absolute UOSM always < isotonic (290 mM)

31. Diabetes Insipidus Back to in-patients!
Impaired thirst or access to water
Elevated serum sodium/OSM
UOSM < 500 mM, USG < 1.017
If serum sodium/OSM not elevated
Not DI!
UOSM and USG are irrelevant

32. Pituitary Surgery Triphasic response to surgery Phase 1: DI
Axonal injury 2° surgery/swelling
Begins after POD #1 (pre-existing DI can occur earlier)
Lasts 1-5d
Phase 2: SIADH
Axonal necrosis of AVP secreting neurons with uncontrolled AVP release
Lasts 1-5 days
Phase 3: DI
Axonal death with cessation of AVP production
Usually permanent

33. PNa U/O 400 150 100 100 50 50 1 6 11 POD # U/O #1 U/O #2 (mEq/L)
(cc/h)
400
150
U/O #1
100
100 50 50
U/O #2 1 6 11
POD #

34. PNa
(mEq/L)
U/O
(cc/h)
400
Na #1
150
U/O #1
100
100 50 50 1 6 11
POD #

35. PNa
(mEq/L)
U/O
(cc/h)
400
150
Na #2
100
100 50 50
U/O #2 1 6 11
POD #

36. PNa U/O 400 150 100 100 50 50 1 6 11 POD # #1 DI #2 Normal Na #1 Na #2
(mEq/L)
U/O
(cc/h)
400
Na #1
150
Na #2
U/O #1
100
100 50 50
U/O #2 1 6 11
POD #

37. DDAVP: 1ug IV/SC = 10 ug IN = 0.1 mg PO
Treatment of DI
Rx Dehydration
NS initially if ECFv contraction
Then IV D5W or enteral free water to lower serum [Na]
1-2 mEq/h if Na > 160, symptomatic (coma, SZ), acute
Otherwise mEq/h
Insensible losses? (0.5 L/d)
Do NOT replace U/O if giving DDAVP
DDAVP (Desmopressin)
Reduces U/O and therefore simplifies fluid therapy
Long t½: duration 8-12h, up to 24h
Therefore use judiciously
DDAVP 1ug IV/SC x 1
Only repeat if breaks-thru again (i.e. becomes hypernatremic with dilute polyuria)
Once nasal mucosa stable can switch to intranasal
Also oral form DDAVP now available
DDAVP: 1ug IV/SC = 10 ug IN = 0.1 mg PO

38. Treatment of DI AVP, Aqueous vasopressin (Pitressin)
Only parenteral form, 5-10 U SC q2-4h
Lasts 2-6h
Can cause HTN, coronary vasospasm
Chlorpropamide (OHA which stimulates AVP secretion)
mg po OD-bid
Only useful for partial DI, can cause hypoglycemia
HTCZ (induces volume contraction which diminishes free water excretion)
mg OD-bid
Mainstay of Rx for chronic NDI
Amiloride (blunts Lithium uptake in distal tubules & collecting ducts)
5-20 mg po OD-bid
Drug of choice for Lithium induced DI
Indomethacin mg po bid-tid (PGs antagonize AVP action)
Clofibrate 500 mg po qid (augments AVP release in partial CDI)
Tegretol mg po od (augments AVP release in partial CDI)