Case discussion and topic reviewPresenter Dr. Pradip KatwalModerator Dr. Thomas JohnDept of internal medicineBPKIHS DHARAN,NEPAL

•67 yrs female

•Presenting complains- fever- 4 days vomiting-4 days loose stool-4 days ( for 2

days) Past h/o- no significant illness

Case summary• Elderly lady without significant pass illness

presented to emergency with h/o low grade fever without chills and rigors, multiple episodes of non-projectile vomiting associated with nausea and watery stool not containing blood or mucus for initial two day and has not passed stool since then. She also complains of weakness and was unable to sit from the supine position.

• No headache, no seizures, no abdominal pain• H/o of treatment in local hospital for two days

before presentation.

At Presentation

• Gcs-14/15• Pulse-113 beats/min• B.P-80/40 mmhg

(supine)• Afebrile• Rr-18 breath/min• JVP-not visible

• Pallor(+) dehydration(+)

skin turgor decreased

CHEST- b/l symmetrical and equal air entry

B/l normal vesicular breath sounds

no creptsCVS - apical impulse 5th ics

medial to MCL S1 S2 M(-)P/A- Soft non tender no organomegalyBowel sound-sluggishCNS-GCS 14/15 higher mental

function cranial nerve-

normal motor- Power 3/5

proximal musle of b/l limbs Rest-WNL sensory-intact no nuchal rigidity

PROVISIONAL DIAGNOSIS

•ACUTE INFECTIVE GASTROENTERITIS IN PRESENTED IN HYPOVOLUMIC SHOCK

Initial management

Inj. Normal saline 1 liter iv bolus

Then Inj.NS 5OO ml iv 6 hourly

Inj.5%dextrose 500 ml 8 hourly

Inj. Ciprofloxacin 200 mg iv BD

Inj. Metronidazole 500 mg iv TDS

Inj Pantoprazole 40mg iv OD

INVESTIGATIONS

•HB-12.2•TLC-14600/MM3•DLC-N70,L30•PT-179000/mm3•URINE RE/ME-

WNL•STOOL RE/ME-

SENT TO CENTRAL LAB

• SUGAR-84• UREA-41• CREATININE-0.8• NA-118• K-2.5• ABG-• PH-7.288• HCO3-14.6• PCO2-28.4• LACTATE-1.0

DIAGNOSIS

•ACUTE INFECTIVE GASTROENTERITIS IN HYPOVOLUMIC SHOCK WITH DYSELECTROLYTEMIA -HYPOKALEMIA -HYPOOSMOLAR HYPOVOLUMIC

HYPONATREMIA-METABOLIC ACIDOSIS

-PARALYTIC ILEUS

Management

Inj. Normal saline 1 liter iv bolus

Then Inj.NS 5OO ml iv 6 hourly with 30meq

KCl in each pint

Inj.5%dextrose 500 ml 8 hourly

Inj. Ciprofloxacin 200 mg iv BD

Inj. Metronidazole 500 mg iv TDS

Inj Pantoprazole 40mg iv OD Inj 3%NS 100 ml TDS

DAY 3 OF ADMISSION

• Subjective- Multiple episodes of vomiting

• Bowel sounds-sluggish• Proximal muscle

weakness

• PULSE-98• B.P.-90/60 mmhg• Afebrile• 16 breath/min• Urine output-400ml

• Sugar-108• Urea-13• Creatinine-1.0• Na-121• K-2.5• Stool re/me-WNL

DISORDERS OF SODIUM BALANCE

HYPONATREMIA

•Hyponatremia is defined as a plasma [Na+] <

135 mEq/L

Hyponatremia• Physiology of Serum sodium concentration

regulation:

1. Renin-angiotensin-aldosterone system

2.Stimulation of thirst

3.Renal handling of filtered sodium

4.Secretion of ADH

Hyponatremia

•Epidemiology:▫Frequency

Hyponatremia is the most common electrolyte disorder

Occurring in 22% of hospitalized patients.

ocw.jhsph.edu

Clinical features

•Symptoms primarily neurological▫Nausea▫Vomiting▫Headache▫Seizure▫Coma

Hyponatremia

•Types▫Hypovolemic hyponatremia▫Euvolemic hyponatremia▫Hypervolemic hyponatremia▫Low solute intake and hyponatremia ▫Pseudohyponatremia

Osmolality• Calculated Plasma Osmolality:

P osm = 2 (Na) + glucose/18 + BUN/2.8

Normal = 290 (275-290 mM)

• Measured osmolality (MO)▫Osmolality measured by osmometer. ▫ works on the method of depression of 

freezing point.• Urine Osmolality:

Normal: 400-500 mM

▫Maximal dilution 50-100 mM▫Maximal concentration 900-1200 mM

HyponatremiaSerum OSM

LOW

Hypotonic hyponatremi

a

NORMALMarked

hyperlipidemiaHyperproteinemi

a

HIGHHyperglycem

iaMannitol

Pseudohyponatremia

Pseudohyponatremia is laboratory error due to high content of plasma proteins and lipids

Expansion of nonaqueous portion of the plasma sample

Errant report of a low ECF [Na+]

HyponatremiaSerum OSM

LOW

Hypotonic hyponatremi

a

NORMALMarked

hyperlipidemiaHyperproteinemi

a

HIGHHyperglycem

iaMannitol

Hyperosmolar hyponatremia

Osmotically active solute other than sodium accumulates in the ECF, drawing water into the ECF and diluting the Na+ content.

Glucose Glycine MannitolSorbitol

100 MG/DL RISE IN PLASMA GLUCOSE

FALL IN PLASMA [NA+] OF 1.6 TO 2.4 MEQ/L

HyponatremiaSerum OSM

LOW

Hypotonic hyponatremi

a

NORMALMarked

hyperlipidemiaHyperproteinemi

a

HIGHHyperglycem

iaMannitol

RESET OSMOSTAT Set point for plasma osmolality is

reduced.

ADH and thirst responses maintain

osmolality at this lower level.

This phenomenon occurs in almost all

pregnant women

PSYCHOGENIC POLYDIPSIA

Urine cannot be diluted to an osmolality less than ~50 mosm/l

A small amount of solute is required in even the most dilute urine.

Assessment of volume status

hypovolemia

U na >20

RENAL LOSSESDiuretic excess

Mineralocorticoid deficiency

Salt losing deficiencyKetonuria

Osmotic diuresis Cerebral salt wasting

syndrome

Una <20

EXTRA RENAL LOSSESVomiting

DIARRHOEATHIRD SPACINGBURNS,PANCREATITIS,TRAUMA

Euvolemia hypervolemia

HYPOVOLEMIC HYPONATREMIA

Develops as sodium and free water are lost and/or replaced by

inappropriately hypotonic fluids

Assessment of volume status

hypovolemia Euvolemia hypervolemia

Acute or chronic renal failure

NEPHROTIC SYNDROMECIRRHOSIS

Cardiac failureU Na >20

U Na<20

Assessment of volume status

hypovolemia Euvolemia

Glucocorticoid deficiencyHypothyroidism

StressDrugs

Syndrome of inappropriate ADH

secretion

hypervolemia

U Na >20

WHAT is inappropriate about SIADH?

Despite the absence of osmotic or volume-related

stimuli

Nonphysiologic release of vasopressin from the

posterior pituitary or an ectopic source

Cerebral salt-wasting

Hyponatremia in cns disease particularly in patients with subarachnoid hemorrhage

Characterized by hyponatremia & extracellular fluid depletion due to inappropriate sodium wasting in the urine

Cerebral Salt Wasting

• Cerebral disease (particularly SAH)

• Mimics SIADH with hyponatremia except

primary defect is salt wasting not water

retention.

• Treatment is NS to correct ECFv contraction

SIADH CSW

Urine Output decreased polyurea

Serum Na low low

Urine Na high high

Serum osm low low

Urine osm high high

CVP high low

Treatment•Distinction between CSW & SIADH is

critically important since the two disorders are managed differently

▫ fluid restriction, the usual first-line therapy for SIADH, may increase the risk of cerebral infarction among patients who actually have CSW

▫Volume repletion with isotonic saline is the recommended therapy in CSW, since it will suppress the release of ADH, thereby permitting excretion of the excess water and correction of the hyponatremia

Diagnostic Testing for classification

Plasma osmolality Urine osmolality Urine sodium concentration

Diagnosis of underlying cause CT head, EKG, CXR if symptomatic CT scan Urea ,Creatinine Serum potassium levels Uric acid TFT

Treatment of Hyponatremia

•Issues to be addressed

Asyptomatic vs. Symptomatic Acute (within 48 hours) vs. Chronic (>48 hours)

Volume status Monitoring response to intervention

calculations• Calculation: Total Body Water (TBW)

▫Men TBW = 0.6 x (kilograms Lean Body Mass)

▫Women TBW = 0.5 x (kilograms Lean Body Mass)

• Calculations based on Total Body Water (TBW)▫Total Body Water Excess (Hyponatremia)

Normal TBW = TBW x (Serum Sodium / 140) Excess TBW = TBW - Normal TBW

▫Free Water Deficit (Hypernatremia) FWD = TBW x (Serum Sodium - 140) / 140

• Calculations: Total Body Sodium Deficit▫Sodium deficit = TBW x (140 - Serum Sodium)

EXAMPLEA 70 years old women is having seizure,her serum sodium is 100

Meq/l.her body wt is 60 kg.INITIAL GOAL-

Increase the sodium concentation to 116 meq or symptoms resolution

ESTIMATE TOTAL BODY WATERO.45 * 60=27

ESTIMATE CHANGE IN SERUM SODIUM(USING one liter of 3% hypertonic saline)

(531-110)/(27+1)=14.39

SYMPTOMATIC PATIENT SO RATE IS 1 MEQ/L/HR FOR NEXT THREE HOUR

For 14.39 meq change - lt. of hypertonic saline 1 lt.For 3 meq change –lt.of hypertonic saline used is (1/14.39)*3

Rate of administration for 3 hours208/3=69.33 ml/hr

Rx Hyponatremia

•When do you need to treat quickly?▫Acute (<24h) ▫severe (< 120 meq/L)▫Symptomatic hyponatremia (seizures, coma, etc.)

• “Quickly” by: ▫ 3% NS, 1-2 mEq/L/h until:

Till Symptoms stops 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 < 10-12 mEq/L/d to prevent myelinolysis

Treatment Hyponatremia

• Act 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 salt tablets

SIADH

Treatment

• Fluid Restriction

• Oral Salt, Hi-protein diet or Urea(30 g/d

• Lasix 20 mg po od-bid

• Demeclocycline 300-600 mg bid)

• Lithium

•Tolvaptan•Most appropriate for significant and

persistant SIADH not responding to furesomide, salt tablets and water restriction

• WATER RESTRICTION.

• The amount of fluid restriction necessary depends on the extent of water elimination.

▫If (Urine Na + Urine K)/Serum Na < 0.5, restrict to 1 L/d.

▫If (Urine Na + Urine K)/Serum Na is 0.5 to 1.0, restrict to 500 mL/d.

▫If (Urine Na + Urine K)/Serum Na is >1, the patient has a negative renal free water clearance and is actively reabsorbing water.

Osmotic Demyelination Syndrome

due to Rapid correctionNeurologic Features

flaccid paralysis Dysarthria dysphagia.

Diagnosis suspected clinically can be confirmed by neuroimaging .

Treatment No effective therapy aggressive plasmapheresis

.

Osmotic Demyelination Syndrome

chronic hyponatremia most susceptible to ODS

Administration of hypertonic saline sudden osmotic shrinkage of brain cells.

Risk factors ▫prior cerebral anoxic injury, ▫hypokalemia,▫Malnutrition▫chronic alcoholism.

•Prognosis▫50% mortality

Hypernatremia(Na+ > 145 mEq)

Introduction• Caused by a relative deficit of water

in relation to sodium which can result from-

Iatrogenic sodium loading

Net water loss

Causes of HypernatremiaNet water lossPure water loss

•Unreplaced insensible losses (dermal and respiratory)

• 10ml/kg per day

•Exercise•Fever•heat exposure•mechamical ventilation

Central diabetes insipidus

•Post-traumatic TumorsCystsHistiocytosisTuberculosisSarcoidosis Idiopathic Aneurysms, meningitis, encephalitis

Nephrogenic diabetes insipidus

•Congenital

•Mutation •

▫X-linked V2 receptors▫aquaporin 2 water channel▫Aquaporin one channel

•Acquired

Renal disease (e.g. medullary cystic disease)

Hypercalcemia

Hypokalemia

Drugs (lithium, demeclocycline, foscarnet,

methoxyflurane, amphotericin B, vasopressin

V2-receptor antagonists)

• Adipsic diabetes insipidus

• Central defect in osmoreceptor function

• Both AVP secretion and thirst

• Gestational diabetes insipidus

• Late pregnancy

• Placental protenease have vasopressinase

activity

Causes of Hypernatremia (cont’d)

Hypotonic fluid loss

• Renal causes

Loop diuretics

Osmotic diuresis (glucose, urea, mannitol)

Post-obstructive diuresis

Intrinsic renal disease

Hypotonic Fluid Loss (cont’d)• Gastrointestinal

VomitingNasogastric drainageEnterocutaneous fistulaDiarrheaUse of osmotic cathartic agents (e.g.,lactulose)

• Cutaneous BurnsExcessive sweating

Causes of Hypernatremia (cont’d)Hypertonic sodium gain

Cushing’s syndrome

Primary hyperaldosteronism

Hypertonic sodium bicarbonate infusion

Ingestion of sodium chloride

Ingestion of sea water

Sodium chloride-rich emetics

Hypertonic dialysis

Clinical Manifestations

•CNS dysfunction ▫Depend on large or rapid increases in

serum Na+ concentration (acute and chronic)

▫Few symptoms until Na+ > 160▫ Affects extremes of ages▫Altered mental status▫seizures • confusion• coma• Subarachnoid hemorrhages • Rabdomyoslsis

Diagnostic approach

•Presence of thrist?•Polyuria?•Source of extra-renal loss

•Deatiled neurological examination

•Extracellular fluid volume Assesment

ECF VOLUME

INCREASED

ADMINISTRATION OF HYPERTONIC NACL OR NACO3

NOT INCREASED

?MINIMUM VOLUME OF MAXIMALLY

CONCENTRATED URINE

MINIMUM VOLUME OF MAXIMALLY CONCENTRATED URINE

URINE OSMOLEEXCERTION RATE<750

mosoml/day Renal

response to

desmopressin

Urine

osmolality

unchanged

Nephrogenic diabetes

insipidus

Unire

osmolality increaseCentral diabetes insipidus

Diuretic Osmotic diuresis

Insensible water lossGastrointestinal water loss

Remote renal water loss

no

noyes

DIAGNOSIS FOR HYPERNATREMIA

• Renal response to hypernatremia is small volume of concentrated (urine osmolality > 800 mOsm/L) urine.

can occur from

The two can be differentiated by quantifying the daily solute excretion (estimated by the urine osmolality × urine volume in 24 hours).

A daily solute excretion > 900 mOsm defines an osmotic diuresis.

urine osmolality <300 mOsm

A suggests complete forms of CDI and NDI

Urine osmolality between 300 and 800 mosm/L

Partial forms of DI as well as osmotic diuresis.

DIAGNOSIS FOR HYPERNATREMIA

The appropriate renal response to hypernatremia is a small volume of concentrated (urine osmolality > 800 mOsm/L) urine.

Submaximal urine osmolality (<800 mOsm/L) suggests a defect in renal water conservation.

A urine osmolality <300 mOsm in the setting of hypernatremia suggests complete forms of CDI and NDI.

Urine osmolality between 300 and 800 mOsm/L can occur from partial forms of DI as well as osmotic diuresis.

The two can be differentiated by quantifying the daily solute excretion (estimated by the urine osmolality × urine volume in 24 hours).

A daily solute excretion > 900 mOsm defines an osmotic diuresis.

RESPONSE TO DDAVP

Complete forms of CDI and NDI can be distinguished by administering the vasopressin analog dDAVP (10 mcg intranasally) after careful water restriction.

The urine osmolality should increase by at least 50% in complete CDI and does not change in NDI. The diagnosis is sometimes difficult when partial defects are present.

Lab measurements

•Serum and urine osmolality

•Urine electrolytes

•Water deprivation test

•Response to DDAVP

ManagementA two-pronged approach: •Addressing the underlying cause:

stopping GI loss, controlling pyrexia, hyperglycemia, correcting hypercalcemia or feeding preparation, moderating lithium induced polyuria

•Correcting the prevailing hypertonicity: rate of correction depends on duration of hypernatremia to avoid cerebral edema

Correction of Hypernatremia•Hypernatremia that developed over a

period of hours (accidental loading)

▫Rapid correction improves prognosis without cerebral edema

▫Accumulated electrolytes in brain rapidly extruded

▫Reducing Na+ by 1 mmol/L/hr appropriate

Rate of Correction (Cont’d)

•Hypernatremia of prolonged or unknown duration

▫A slow pace of correction prudent▫ Full dissipation of brain solutes occurs

over several days▫Maximum rate 0.5 mmol/L/hr to prevent

cerebral edema▫A targeted fall in na+ of 10 mmol/L/24 hr

Goal of Treatment•Reduce serum sodium concentration to

145 mmol/L

•Make allowance for ongoing obligatory or incidental losses of hypotonic fluids that will aggravate the hypernatremia

•In patients with seizures prompt anticonvulsant therapy and adequate ventilation

Administration of Fluids•Preferred route: oral or feeding tube•IV fluids if oral not feasible•Except in cases of frank circulatory

compromise, isotonic saline is unsuitable•Only hypotonic fluids are appropriate-

pure water, 5% dextrose, 0.2 % saline, 0.45% saline-the more hypotonic the infusate, the lower the infusion rate required

▫CORRECTION OF HYPERNATREMIA IS ACCOMPLISHED BY CALCULATING FREE WATER DEFICIT BY THE EQUATION:

• The change in [Na+] from the administration of fluids can be estimated as follows:

• Δ[Na+] = {[Na+i] + [K+

i] - [Na+s]} ÷ {TBW +

1}

Management of hypernatremia

•Water deficit + ongoing water loss +insensible loss

•Correct the water deficit over 48 to 72 hours

•Avoid correction of plasma Na by >10 mM/day

WATER DEFICIT

I. TBW is estimated by multiplying lean weight (kg) by 0.5 in men (rather than 0.6) and 0.4 in women.

II.Free water deficit = {([Na] - 140)/140} × (TBW)

Ongoing water losses:-

CALCULATE ELECTROLYTE FREE WATER CLEARANCE

C H2O= V(1-UNa+Uk)/PNa

Insensible loss-1o ml/kg per day

Diabetes insipidus is best treated by removing the underlying cause

I. CENTRAL DIABETES INSIPIDUS

Administration of dDAVP, a vasopressin analog.

II. NEPROGENIC DIABETES INSIPIDUS.

A low-Na+ diet combined with thiazide diuretics will

decrease polyuria through inducing mild volume depletion.

Decreasing protein intake will further decrease urine output by minimizing the solute load that must be excreted.

HOSPITAL COURSE•PATIENT IMPROVED DURING HER

COURSE OF STAY IN HOSPITAL BUT HAD PERSITANT HYPOKALEMIA AND WEAKNESS OF PROXIMAL MUSCLE DESPITE POTASSIUM SUPPLEMENT.

D5 D6 D7

SODIUM 130 140 145

POTASSIUM

3.1 3.1 3.8

UREA 49 10

CREATININE

1 O.7

•DUE TO PERSISTEN HYPOKALEMIA SERUM MAGNESIUM LEVELS WAS EVALUATED

CALCIUM MAGNESIUM

DAY 7 6.9 O.41

DAY 8

Mechanism of Hypokalemia in Magnesium Deficiency

DAY 8 ADMISSION

•SHE IMPROVED GRRADUALLY•NO DIFFICULTING IN LIFTING HER

HEAD•NO DIFFICULTY IN WALKING

PATIENT WAS DISCHARGED ON DAY 9.

•Thank you

Refrences•HarrisonsPrinciples.of.Internal.Medicine.

18th.Edition

•Raoof Manual of critical care •Washington Manual® of Medical

Therapeutics, The, 34rd Edition.

•HYPONATREMIA REVIEW ARTICLE, Adrogué HJ, Wesson DE. The New England Journal of Medicine 2004:205-84