PROF.DR.P.VASANTHII’S UNITDR.V.GIRIDHARAN

A CASE OF HYPONATREMIA

• 68 yr old lady known diabetic and hypertensive for the past 2 years presented to zerodelay with h/o

• chest pain,breathlessness -3 hrs duration• No h/o palpitation• No h/o sweating• No h/o decreased urine output• No h/o cough or expectoration• No h/o fever• No h/o head ache• No h/o myalgia

• No h/o abdomen pain• No h/o loose stools• No h/o vomiting• No h/o weakness of limbs• No h/o any visual distrubances• No h/o seizure • No h/o syncope• No h/o dizziness• No h/o bladder /bowel distrubances• No h/o loss of conciousness• No h/o altered behaviour

ON EXAMINATION• Pt concious,oriented• Anxious• Dyspnoeic/tachypnoeic (28/min)• Afebrile• No pallor• Not cyanosed• No clubbing• No icterus• No pedal edema• Jvp not elevated• No lymphadenopathy

• S1 s2 –present,no murmur• RS-nvbs present, no crepitations• P/A- soft, no tenderness no organomegally bowel sounds +• CNS-nfnd

• Known diabetic,hypertensive for past two years–chest pain for 4 hrs ,

• Vitals stable,• ECG-ST elevation 1,Avl,v2-v4,• Echo-hypokinesia distal 2/3 of ivs, aw,apex.• EF-45./.• Thrombolysed with streptokinase.• In ICCU with cardiac drugs

• No other positive history .• Prior h/o right hemiparesis 2 yrs ago but recovered• Pt was concious ,well oriented at admission and

after lysis.• Pt was dyspnoeic ,tachypnoeic (rate 28/min)• Not febrile• No pallor• Not cyanosed,no clubbing,no icterus• Jvp –not elevated

DAY 1

• S1 s2 +,no murmur.• S3,s4 not heared.• Rs-nvbs ,no crepitations• P/A-soft• CNS-NFND

DAY 1

• BP-156/90• Pulse-106/min• SPO2-96./. With 4 lit/min o2 (mask)• ECG- ST elevation lead 1,aVL ,v2-v4

DAY 1

BLOOD SUGAR 268 mg/dl

UREA 26 mg/dl

S.CREATININE 0.8 mg/dl

Na+ 139 mg/dl

K+ 3.9 mg/dl

CPK MB 32 UNITS/L

URINE KETONES NEGATIVE

DAY 1PARAMETER RESULT

HB ./. 10.2 g/dl

TOTAL COUNT 8,600

DIFFERENTIAL COUNT 65/30/5

ESR 8/16

PLATELET COUNT 2.4 lakhs

RBC 3 million

PCV 30

DAY 1

• Pt was thrombolysed with streptokinase• Pt doing well till that afternoon• After 5 pm on that day pt developed altered

sensorium• Neurological examination shows paucity of

movement on right side • Pt was drowsy,disoriented• Suspected ICH ( complication of lysis)

DAY 1

• Emergency CT taken –didn,t show any haemorrhage

• Infarct seen in left cerebellar hemesphire• MRI was planned next day• Neuro opinion was obtained• Advised MRI/electrolytes• Mean while pt was on cardiac drugs

DAY 1

BLOOD SUGAR 256 mg/dl

UREA 31 mg/dl

S.CREATININE 1.1 mg/dl

Na+ 107 mg/dl

K+ 4.2 mg/dl

• Pt was treated cautiously with iv fluid normal saline 50-75 ml/hr ,while monitoring signs for volume overload and urine output

DAY 2TIMING Na+ LEVELS

MORNING LOW RANGE

AN 111 meq/l

EVENING 108 meq/l

MRI BRAIN ACUTE LEFT CEREBELLAR INFARCT CHRONIC INFARCT LEFT TEMPARO-PARIETAL REGION

1 •SHT /T2DM

2 •ACS/AWMI

3 •CVA/CEREBELLAR INFARCT

SHT/T2DM

ACS/AWMI

CVA/ACUTE CEREBELLAR INFARCT

HYPONATREMIA

?

What next?

• In the back ground of

SHT DM2 OLD CVA ACS/AWMI ACUTE LT CEREBELLAR

INFARCT HYPONATREMIA

• Hypo or hypernatremia is primarily is a disorder of water balance

hyponatremia

• Na+ <135 meq/l• Subdivided diagnostically into three

groups,depending upon clinical history and volume status.

hyponatremia

hypovolemic

euvolemic

hypervolemic

Hyponatremia is classified according to volume status, as follows

• Hypovolemic hyponatremia: decrease in total body water with greater decrease in total body sodium

• Euvolemic hyponatremia: normal body sodium with increase in total body water

• Hypervolemic hyponatremia: increase in total body sodium with greater increase in total body water

IN OUR PATIENT

HYPONATREMIA

1)ACS2)AWMI

3)MILD PEDAL EDEMA4)NO JVP

1)SHT2)T2DM/HYPERGLYCEMIA

3)CREATININE-1.2/INTERSTITIAL NEPHRITIS

1)OLD CVA2)RECURRENT CVA

3)ACUTE CEREBELLAR INFARCT

HYPERVOLEMIA? HYPOVOLEMIC? EUVOLEMIC/HYPOVOLEMIC?

PSEUDO HYPONATREMIA

• Hyperlipidemia • Hyperproteinemia• Hypertonic (or translocational) hyponatremia

occurs when osmotically active solutes (glucose or mannitol) draw water from cells.

• For each increase of 100 mg /dl of glucose, sodium declines by 1.6 to 2.4 meq/l

CONFUSED OF HYPO OR EUVOLEMIC?

• When diagnostic uncertainty remains, volume contraction of the extracellular fluid can be ruled out by infusing 2 liters of 0.9% saline over a period of 24 to 48 hours.

• Even though 0.9% saline is not the preferred treatment for SIAD, it is usually safe when the baseline urinary osmolality < 500 mOsm /kg

• correction of the hyponatremia suggests underly ing volume depletion of extracellular fluid.

SERUM OSMOLALITY 267 mOsm/kg

URINE OSMOLALITY 281 mOsm/kg

URINE SODIUM 95 meq/l

Urine chloride 83 mOsm/l

Urine spot k+ 7 meq/l

Thyroid function test

T4 2

TSH 4

7 AM CORTISOL

X RAY CHEST NORMAL

USG ABDOMEN NORMAL KIDNEY SIZE ,1.1 mm left renal calculi,resr normal

S.URIC ACID 4 mg/dl

ADH

• Synthesized in hypothalamus• Transported down to posterior pituitary• Released in response to hyperosmolality (major stimuli,

mediated through osmoreceptors in hypothalamus) or hypovolemia (via baroreceptors in left atrium, aortic arch, etc)

ADH

• Binds to V2 receptors in collecting tubules– stimulates cyclic adenosine monophosphate– leads to insertion of aquaporin-2 channels into apical

membranes

• The goal is to facilitate the transport of solute-free water

SIADH => SIAD• A slight misnomer• The name implies inappropriate secretion• 1/3rd of pts do secrete AVP independent of plasma osmolality• Others exhibit reset osmostat – AVP is fully supressed, but

serum Na level is lower than nl• AVP levels may be undetectable in some pts• Some aquaporin mutations lead to concentrated urine in the

absence of AVP• Therefore, the new term, Syndrome of Inappropriate

Antidiuresis (SIAD) has been proposed

Patterns of plasma levels of arginine vasopressin (AVP; also known as the antidiuretic hormone), as compared with plasma sodium levels in patients with SIAD, are shown. Type A is characterized by unregulated secretion of AVP, type B by elevated basal secretion of AVP despite normal regulation by osmolality, type C by a "reset osmostat," and type

D by undetectable AVP. The shaded area represents normal values of plasma AVP. Adapted from Robertson

DOES AVP NEEDS MEASUREMENT?

• Measurement of the serum level of arginine vasopressin is not recommended routinely, because urinary osmolality above 100 mOsm per kilogram of water is usually sufficient to indicate excess of circulat- ing arginine vasopressin.

Neurological adaptation

• The severity of neurologic symptoms correlates well with the rate and degree of the drop in serum sodium. A gradual drop in serum sodium, even to very low levels, may be tolerated well if it occurs over several days or weeks, because of neuronal adaptation.

SIADH

Hypothalamus receives feedback from:

• Osmoreceptors• Aortic arch baroreceptors• Carotid baroreceptors• Atrial stretch receptors

Any increase in osmolality or decrease in blood volume will stimulate ADH secretion from posterior pituitary.

SIADH - pathophysiologyADH-induced water retentionDilutional hyponatremiaVolume expansion -> secondary natriuresis

Sodium and water lossPotassium loss

Result: Euvolemic hyponatremiaReduced serum osmolalityIncreased urine osmolalityIncreased urine sodium

SIADH - treatment

Treat the underlying cause, if knownFluid Restriction – commonly 800-1000mL/dCorrect Na+ deficit – no more than 10mEq/L

in 24 hours, 18mEq/L in 48 hours0.9% NaCl3% NaClNaCl enteral tablets – 2-3g TIDAdd a loop diuretic

Malignant Diseases

Pulmonary Disorders

Disorders of CNS Drugs Other Causes

CarcinomaLungSmall cellMesotheliomaOropharynxGastrointestinal tractStomachDuodenumPancreasGenitourinary tractUreterBladderProstateEndometriumEndocrine thymomaLymphomasSarcomasEwing's sarcoma

InfectionsBacterial pneumoniaViral pneumoniaPulmonary abscessTuberculosisAspergillosisAsthmaCystic fibrosisRespiratory failure associated with positive-pressure breathing

InfectionEncephalitisMeningitisBrain abscessRocky Mountain spotted feverAIDSBleeding and massesSubdural hematomaSubarachnoid hemorrhageCerebrovascular accidentBrain tumorsHead traumaHydrocephalusCavernous sinusthrombosisOtherMultiple sclerosisGuillain-Barré syndromeShy-Drager syndromeDelerium tremensAcute intermittent polyphyria

Drugs that stimulate release of AVP or enhance its actionChlorpropamideSSRIsTricyclic antidepressantsClofibrateCarbamazepineVincristineNicotineNarcoticsAntipsychotic drugsIfosfamideCyclophosphamideNonsteroidal anti-inflammatory drugsMDMA (ecstasy)AVP analoguesDesmopressinOxytocinVasopressin

Hereditary (gain-of-function mutations in the vasopressin V2 receptor)IdiopathicTransientEndurance exerciseGeneral anesthesiaNauseaPainStress

• SIAD may be difficult to distinguish from cerebral salt wasting, a syndrome of hyponatremia and ex- tracellular-fluid volume depletion in patients with insults to the central nervous system.43,44 The pri- mary feature that differentiates cerebral salt wast- ing from SIAD is extracellular-fluid volume deple- tion, but clinical assessment of volume status is imprecise

Cerebral Salt Wasting

Hyponatremia caused by impaired renal tubular function -> inability of kidneys to conserve salt

Salt wasting leads to volume depletionTwo theories:

Impaired sympathetic neural input -> failure of aldosterone release -> no sodium resorption

BNP release decreases sodium resorption, inhibits renin/aldosterone release, decreases autonomic outflow at level of brainstem

Cerebral Salt Wasting

Commonly occurs in subarachnoid hemorrhage population (7%)

Carcinomatous, infectious meningitisEncephalitisPoliomyelitisCNS tumorsCNS surgery – usually within the first 10 days

CSW

Cerebral Salt Wasting

• Treat with volume repletion– 0.9% NaCl– 3% NaCl is sometimes warranted– Fludrocortisone

MANAGEMENT OF HYPONATREMIAWater deficit

1. Estimate total-body water (TBW): 50% of body weight in women and 60% in men2. Calculate free-water deficit: {([Na+]-140)/140} x TBW3. Administer deficit over 48–72 h, without increasing the plasma Na+ concentration by >10 mM/24 hOngoing water losses

4. Calculate electrolyte-free water clearance, CeH2O:where V is urinary volume, UNa is urinary [Na+], UK is urinary [K+], and PNa is plasma [Na+]Insensible losses

5. 10 mL/kg per day: less if ventilated, more if febrile

Total

6. 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

Remember....• Elevated BUN and creatinine in routine chemistries also can indicate renal dysfunction

as a potential cause of hyponatremia,• whereas hyperkalemia may suggest adrenal insufficiency or hypoaldosteronism.• Serum glucose also should be measured; plasma Na+ concentration falls by 1.6 to 2.4

mM for every 100-mg/dL increase in glucose due to glucose-induced water efflux from cells; this "true" hyponatremia resolves after correction of hyperglycemia.

• Measurement of serum uric acid also should be performed; whereas patients with SIAD-type physiology typically will be hypouricemic (serum uric acid <4 mg/dL),

• volume-depleted patients often will be hyperuricemic.• In the appropriate clinical setting, thyroid, adrenal, and pituitary function should also

be tested;• hypothyroidism and secondary adrenal failure due to pituitary insufficiency are

important causes of euvolemic hyponatremia, • whereas primary adrenal failure causes hypovolemic hyponatremia• A cosyntropin stimulation test is necessary to assess for primary adrenal insufficiency.