2. TBW=2/3(ICF)+1/3(ECF)=0.6* LBW in Male,0.5*LBW in females
ECF =INTRAVASCULAR(plasma water)+INTERSTITIAL(extravascular)
with ratio of 1:3 to 1:4
Normal plasma osmolality-275-290 mosmol/kg
Maximal urine osmolality our kidney can attain -1200 mosmol/kg
Minimal urine osmolality our kidney can attain-50 mosmol/kg
requiring 12ltr/day urine output.
Minimum urine output required to excrete daily solute
load(amount of salt consumed per day i.e. Roughly 600 to 800
mOsm/day) is 600/1200=500ml/day.
General Principle
3. Major ECF electrolyte =Sodium (85-90%)
Change in sodium concentration reflects-disturbed water homeostasis .
Contd.
Water lost in stool=200ml/day and produced by metabolism=250-350
ml/day.
Insensible losses=400 to 500ml/day (increase by 100-150ml/day for each
1 degree C rise above 37 degree C.
4. WATER BALANCE:-
Water intake-Thirst by Osmorecepotors with threshold
>295mosm/kg, in anterolateral hypothalamus(ineffective osmoles like
Urea-no role in thirst)
Water excretion-ADH with major stimulus for its secretion is
hypertonicity with threshold of 280-290mosmol/kg Nonosmotic
stimuli for ADH release-Arterial Effective circulating
volume,nausia,pain,stress,hypoglycemia, Pregnancy,numerous drugs.
5. SODIUM BALANCE :-
INTAKE:- In Western Diet 150 mmol of NaCl/Day normally exceeds
basal requirements-ECF Volume expansion promotes enhanced
Na+ excretion to maintain balance.
EXCRETION:-Multiple factors
Change in effective circulatory volume ➡️ Parallel change in GFR
Major regulator of Na+ is Tubular Na+ reabsorption.
(2/3 approx absorbed electro neutrally and iso oosmotically in
PCT.)
Rest 1/3 absorbed in Thick ascending Loop of Henle via apical
Na+K+2Cl- Co Transporter as an electro neutral active process.
DCT reabsorption 5% mediated by thiazide sensitive Na+Cl-
Cotransporter.
Final reabsorption in medullary and cortical CD.
6. Na+<135meq/l (primarily water balance or distribution disorder.)
Symptoms:- Primarily neurogenic- Related to Osmotic intracellular
water shift ➡️ Cerebral edema.
Severity
Acute condition(<2 Days) :-
Nausea and Malaise with Na+125
<125-Headache,Lethargy,Confusion and Obtundation
<115-Stupor,Seizures and coma
HYPONATREMIA
Magnitude of Hyponatremia
Rapidity of disease
7. Contd.
Chronic condition(>3 days) :-Osmotic Adaptation tend to
minimise the symptoms
Diagnosis:-History and Physical Examination for ECF Volume status
and Effective ciculatory volume.
8. Hyponatremia
(Too much water not enough salt)
Check Serum Osmolality
(Serum Osmolality =2[Na+]+Glucose/18+BUN/2.8)
Approx =2*[Na]+10
Hypo-osmolar
<280
Iso-osmolar
280-295
(Pseudohypernatremia)
Hyperosmolar
>295
9. Iso osmolar/Pseudohyponatrmia:-
Old lab Artifact
Underestimate level when TG high,Protein high>10,
Hyper-osmolar:-
Infact sodium is normal
High Glucose/Mannitol dilutes Na+
Corrected Na for high Glucose=[Na+] +2.4 for each 100mg/dl increase
in blood glucose.
Rx-Correct glucose
11. HYPOTHALAMUS
Posterior Pituitary
ADH
1. INCREASE IN OSMOLALITY(hypothalamus)
2. DECREASE IN VOLUME(baroreceptor/Vagus)
➕
V1(Squeeze)
V1a and V1b
V2 on P Cell of CD
(GPCR)
Via adenyl cyclise
Aquaporin 2
insertion into luminal
surface.
At high conc
Vasoconstriction
Induce glycogenolysis
Inc ACTH release
12. Hypovolemic Hyposmolar Hyponatremia
Loss of salt more than water
Assess Renal Reaction
(Urine Sodium)
Kidney got this
UNa+ <10
Fault at kidney level
UNa+ >20
GI Loss-Diarrhea,Vomiting
Skin loss-
Sweating,Burns,pancreatitis
Drugs-Ace inhibitors,Thiazide
Other- Nephropathy,Mineralocorticoid
insufficiency,Bicarbonaturia, Ketonuria
Cerebral salt wasting syndrome
(Including Head injury-increased ADH-Increased BNP-
decreased Aldosterone.) also show refractory
hypotension
13. Urinary osmolality
Euvolemic Hypo-osmolar Hyponatremia
<100 mOsm/L
(Appropriate)
>100 mOsmol/l
(Inappropriate)
Primary Polydipsia
Beer Protomania
Post-TURP
SIADH
R/O Hypothyroidism
& Decreased
Cortisol,drugs,stress
UNa+ >20meq/dl
Urine Osmolality is low but
higher than that of plasma
14. SIADH
Characterised by hyponatremia caused by a sustained release of ADH
in absence of osmotic and non osmotic stimuli.
Diagnostic criteria are:-
1. Hyponatremia
2. ⬇ plasma Osmolality (<280 mosm/l)
3. Inappropriately increased urine Osmolality (>100 mosm/dl)
4. Urine sodium >20 meq/l (sodium excretion due to increase in ECF
occur because sympathetic nervous system,RAAS and Atrial
natriuretic factor release are preserved)
5. Normal thyroid and adrenal functions
15.
16. Urinary Osmolality low but higher than that of plasma
Low BUN and low serum Uric acid levels (because of
dilution and increased clearance in personae to volume
expanded state)
Glucocorticoids exert a negative feedback on AVP
release by the posterior pituitary so that hydrocortisone
replacement in these patients will rapidly normalize the
AVP response to osmolality, reducing circulating AVP.
17. HYPERVOLEMIC HYPO-OSMOLAR HYPONATREMIA
Fluid overall increase but in wrong space.
Body looks it as hypovolemic.
Assess Kidney function
(kidney should be peeing a diluted urine[RAAS])
Urine Na+ <20meq/l
Kidney working fine
CHF(Dec Renal Perfusion)
Liver Cirrhosis (Dec Intravascular
volume +Splanchnic Vasodilation)
Nephrotic Syndrome
Urine Na+ >20meq/l
Renal Insufficiency
Renal Failure
Rx-Loop Diuretics.In Liver failure Spironolactone / Octreotide
18.
19.
20. TREATMENT
Issues:-
1. Rate of correction
2. The appropriate intervention
3. Presence of other underlying disorder
Rate Of Correction-depends on acuity of its occurrence and
neurological symptoms.
Risk of Rapid overcorrection➡️CPM➡️Quadriplegia
21. B. Chronic Asymptomatic hyponatremia:-
Risks of iatrogenic injury increases actually.
Osmotic adapted brain cells➡️osmotically destabilize after rapid
correction.
Some suggest even modest rate for this i.e. 5-8 mEq/l over 24
hours.
A. Acute Symptomatic Hyponatremia:--
If Severe Use Hypertonic Saline or Saline Hypertonic to Urine of that patient.
Rate of correction should never be >10 to 12 meq/l over the 24 hr.
In Severe Hyponatremia-immediate rise needed should not be > 1-2
meq/l/hr for first 3 to 4 hours
22. ✔ Change in [Na+] after giving 1 litre of fluid is determined by
🔼[Na+]={[iNa+]+[iK+]-[sNa+]}/{TBW +1}
(TBW=0.6✖LBW in Men and 0.5✖LBW in women)
✔ Desired Rate of Correction in meq/l/hr devided by Delta
[Na ] gives us rate of administration of that particular fluid in
l/hr.
23. Example-80kg woman is seizing.Her Na is 108 meq/l.calculate rate
of type of fluid u will use in this case.??
ANS= IV Solution Osmolality Sodium Glucose
D5W 278 0 50
0.45% NaCl 154 77 0
0.9% NaCl 304 154 0
3% NaCl 1024 514 0
RL 274 130 0
RL has 109 meq/l chloride,4 meq/l of
K+,1.5 meq/l of Ca2+ and 28 meq/l
Lactate.
24. Ans 200ml/ hr for 3 to 4 hrs and not more than 1 lt total in a day.
Rate of correction = 1 to 2 meq/l/hr for first 3 to 4 hours
Means of correction = hypertonic saline having Nai➡️513 meq/l
One litre of 3% saline will raise Na+ by
🔼Na= (513-108)/(80✖0.5+1)=10 meq/l
Rate = (2 meq/l/hr)/(10 meq/l per litre of 3%NS) = 200ml/hr for first 3
to 4 hrs
To prevent change of >10 to 12 meq/l over 24 hr, no more than 1ltr
should be given.
25. For Hypovolemic asymptomatic hyponatremia:-Isotonic saline.
For Hypervolemic asymptomatic hyponatremia:-in CHF and
Cirrhosis.Although effective volume is decreased.
Water restriction and increasing water diuresis helps.
Oral intake<Daily urine output.
Use of loop diuretics -Reduce Cortico-medullary osmotic
gradient by decreasing medullary osmolarity hence render ADH
ineffective.[So Free water excretion>Na loss]
Role of Vasopressin # may also be useful in addition to
SIADH(Euvolemic)
26. For Euvolemic Asymptomatic Hyponatremia (SIADH):-
First line therapy = Water Restriction and correction of any
contributing factors(Nausia,Pneumonia,Drugs)
Water restriction:-roughly to 500ml less than urinary output.
o If (Urine Na+ + Urine K+)/Serum Na+ < 0.5 ➡️1 ltr /day
o If (Urine Na+ + Urine K+)/Serum Na+ 0.5 to 1 ➡️500ml/day
o If (Urine Na+ + Urine K+)/Serum Na+ >1 ➡️ Means negative renal free
water clearance with active
reabsorption of water.Any
amount of water given may
be retained.
Therapy directed to enhance free water excretion—Vaptans,Li and
Demeclocycline(DOC 150-300mg PO tds to qid).
27. For Euvolemic hyponatremia with severe symptoms or signs:-
Hypertonic saline can be infused at roughly <0.05 ml/kg body
weight in per minute with hourly sodium levels measured
until Sodium increases by 12 mew/l or to 130
meq/l,whichever occurs first.
Coinivaptan, a non peptide V2 receptor antagonist, given either
PO (20-120 mg bid) or iv (10-40 mg)
28. Plasma [Na+] >145 meq/L (a Hyperosmolar Condition)
Primary Na+ gain or a Water Deficit due to -
o Impaired Thirst Response - Physical restrictions,or mentally impaired
patient
o Due to Water loss :-
1. Nonrenal Water Loss—Skin and respiratory tract(insensible),GI loss like diarrhea
mainly osmotic diarrhoea and viral gastroenteritis .
2. Renal water Loss - Either Osmotic Diuresis or DI.
• Osmotic Diuresis:-High osmolar feeds,and glycosurea,stress dose of steroid.
• DI-CDI or NDI (Li, Demeclocycline, amphotericin, hypercalcemia, Hypokalemia,
medulary wash out and intrinsic renal ailment.
HYPERNATREMIA
29. o Hypernatremia due to Primary Na + gain :-
1. After repeat hypertonic saline
2. Chronic mineralocorticoid Excess.
o Transcellular shift of water from ECF to ICF :-In transient
intracellular hyperosmolality as in Seizures or
Rhabdomyolysis.
30. Clinical presentation:-
Contraction of brain cells➡️Altered mental
status,weakness,neuromuscular irritability,Focal
neurological deficit,even coma and Seizures.
If CDI/NDI - Polyuria and thirst.
Signs of volume depletion or neurological signs are
generally absent unless associated with thirst
abnormality.
32. Issues:-
1. rate of correction
2. the appropriate intervention
3. presence of other underlying disorders
Rate of correction-depends on acuity and neurological
symptoms.
Should be reduced by roughly 10 to 12 meq/l/day in
Symptomatic hypernatremia.
In Chronic asymptomatic case-more moderate rate 5 to 8
meq/l/day.
TREATMENT
33. Intervention:
By administration of Water preferably by mouth/RT
IVF- D5W,or 1/4NS
Free Water Deficit ={([Na+]-140)/140}✖TBW
It is although helpful in estimating water deficit but don't tell
rate.
Ongoing Water Losses
Calculate electrolyte-free water clearance, CeH2O
CeH2O = V (1 − UNa + UK)/Pna
where V is urinary volume, UNa is urinary [Na+], UK is urinary [K+],
and PNa is plasma [Na+]
34. Insensible loss:-
10 mL/kg per day: less if ventilated, more if febrile
Total:-
Add components to determine water deficit and
ongoing water loss; correct the water deficit over 48–
72 h and replace daily water loss.
Avoid correction of plasma [Na+] by >10 mM/d
35. Specific therapy for underlying cause :-
Hypovolemic Hypernatmia – IVF/Oral fluids
Primary Na gain hypernatremia-Stop iatrogenic Na+
DI without Hypernatremia-means thirst mechanism is intact .Rx is
for symptomatic polyuria only.
CDI-Vasopressin analog DDAVP
NDI-Low Na+ diet combined with Thiazide diuretic will decrease
polyuria through inducing mild volume depletion.IT enhances
proximal reabsorption of salt and water,decreasing free water loss.
Low protein diet-futher decrease urine output by minimizing
solute load that must be excreted.
36. Example question:A 70 kg man with diarrhea(2ltr/d)
from laxative abuse presents with obtundation. And
[Na+]=164meq/l,[K+]=3.A replacement fluid of D5W with
20meq KCL/L is chosen. Give Fluid infusion rate.??
Ans=
IV Solution Osmolality Sodium Glucose
D5W 278 0 50
0.45% NaCl 154 77 0
0.9% NaCl 304 154 0
3% NaCl 1024 514 0
RL 274 130 0
37. Ans= D5W at 500ml/hr for first 3 hrs and total of 3 lt in a
day
Choice of fluid= D5W with 20 meq KCL/litre
🔼Na= (0-164)/(70✖0.5+1)=-4 meq/lt
Total fluid req per day=12/4=3 litre over a day
Rate in first 3 to 4 hr = (2 meq/lt/hr)/(4meq/lt)=500ml/hr for
first 3 hrs at the max
Not more than 3 lt should be given in a day.
