HYPONATEREMIA AND HYPERNATREMIA

DR ASEEM WATTS

DNB INTERNAL MEDICINE

MODERATOR -DR MEGHNA KABRA

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

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.

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.

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.

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

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.

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-osmolar280-295

(Pseudohypernatremia)

Hyperosmolar>295

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

Hypo-osmolar Hyponatremia(true Hyponatremia)

Assess Volume status Vitals:-BP,HR,Orthostatic

JVP-Overload Axillary Moisture Chest S4-Overload

Pulmonary-BiBasilar Crackles Pedal Edema

Lab:-Uric acid,BNP-<50,Specific gravity

Hypovolemic (High ADH) Euvolemic Hypervolemic

(High ADH)

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 concVasoconstriction

Induce glycogenolysisInc ACTH release

Hypovolemic Hyposmolar Hyponatremia

Loss of salt more than water

Assess Renal Reaction(Urine Sodium)

Kidney got this UNa+ <10

Fault at kidney levelUNa+ >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

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/dlUrine Osmolality is low but higher than that of plasma

SIADHCharacterised by hyponatremia caused by a sustained release of ADH

in absence of osmotic and non osmotic stimuli.

Diagnostic criteria are:-1. Hyponatremia2. ⬇ 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

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.

HYPERVOLEMIC HYPO-OSMOLAR HYPONATREMIAFluid 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

TREATMENT

Issues:- 1. Rate of correction2. 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

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

✔ 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.

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.

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.

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)

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 /dayo 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).

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)

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

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.

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.

DIAGNOSTIC APPROACH

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

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+]

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

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.

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

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.

Vaptans