Sodium disorders

Prof Tahir Shafi

Overview

Hyponatremia Pathophysiolgy Diagnostic approach Clinical sequeli

Acute Chronic hyponatremia

Hypernatremia Diffirenial diagnosis, diagnostic approach Management

Function of body sodium

Major electrolyte of ECF Responsible for maintaining serum &

ECF osmolality directly, Intracellular fluid and total body fluids indirectly

Serum osmolarity milliosmoles per liter =

18 6 Blood Sugar

2 (SNa+) + Blood Urea+

Osmolality milliosmoles per Kg

Body sodium distribution

Total body sodium 60 mmole/kg ECF 50% ICF 5 % BONE 45 % Exchangeable 70% Normal serum sodium 135-145 meq/l Normal inracellular sodium 10-12

meq/l

Definition hyponatremia

Serum sodium levels less than 135 meq/l

Disorder of water metabolism Relative excess of water in ECF Does not reflect total body sodium

which could be normal, high or low

Definition hypernatremia

Serum sodium levels >145 meq/l Disorder of water metabolism Relative water deficit in ECF Does not reflect total body sodium

which could be normal, high or low

Change in serum / ECF osmolality change in cell volume

Na

NaNa

NaNa

NaNa

Na

KK

KK

KKKK

KK

KKKK

KK

KK

KK

KK

ICF ECF

Na

Na Na

Na

Na

Na

Na

KK

KK

KKKK

KK

KKKK

KK

KK

KK

KK

ICF ECF

Na

Na

Na

Na

Na

Na

Effects of cell expansion/shrinkage apparent in case of brain cells

Brain Edema

What Prevents Hyponatremia

HigherintegrativecentersThirst inhibited

ingestion of waterdecreased

ADH

Excretion of waterIncreased

Hyportonicity

xSerum SodiumIncrease in osmolality

What Prevents Hypernatremia

HigherintegrativecentersThirst stimulated

ingestion of waterincreased

ADH

Decreased excretion of water

Hypertonicity

Serum Sodiumin osmolality

Impact of Hyponatremia & Hypovolemia on ADH Secretion

Retention f waterDecrease urine output

Hypotonicity

Arterial barorecpters

Cardiopulmonary receptors

Visceral osmorecptors

Hypovolemia

ADH

HypotonicityHypovolemia

Regulation of serum osmolality

Plasma ADH declinesThirst inhibited

Plasma ADH risesThirst stimulated

Regulation of ECF volume

Osmoregulation Volume regulation

What is sensed Plasma osmolality Effective circulatory volume

Sensors Hypothalamic osmoreceptors

Carotid sinus Afferent arterioleAtria

Effectors ADH/vasopressin thirst

Sympathetic nervous system, RAASANP/BNPVasopressin

What is affected Urine osmolality, water intake

Urinary sodium excretion

Black and Rose, Manual of Clinical Problems in Nephrology 1988

Water Reabsorption by Kidneys

80 % reabsobed in proximal tubuleObligatory reabsorption

Remaining 20 %Facultative reabsorption

Water Reabsorption by Kidneys

80 % reabsobed in proximal tubuleObligatory reabsorption

Remaining 20 %Facultative reabsorption

GFR = 100 ml/min144 liters in 24 hours80 % of 144 liters reabsorbed inProximal tubule = 115.2 L

Reabsorption of remaining 20 % i.e. 28.8 Liters under influence of ADH

Maximum amount of free water excretion

Water reabsorption by kidneys

80 % reabsobed in proximal tubuleObligatory reabsorption

Remaining 20 %Facultative reabsorption

GFR = 10 ml/min14.4 liters in 24 hours80 % of 14.4 liters reabsorbed inProximal tubule = 11.52 L

Reabsorption of remaining 20 % i.e. 2.88 Liters under influence of ADH

Maximum amount of free water excretion

Negative Free Water Excretion

1. Delivery

Filtration

Reabsorption

2. Separation

3. Control

Free water excretion

ADH Present

Free Water Excretion

1. Delivery

Filtration

Reabsorption

2. Separation

3. Control

Free water excretion

No ADH

Clinical Features of Hyponatremia

Headache Nausea.Vomiting Muscle cramps Lethargy. weakness Restlessness Disorientation, Ataxia, falls

fractures Depressed reflexes

Seizures Coma Permanent brain

damage Respiratory arrest Brain stem

herniation Death

Chronic Acute

Bone injury from hyponatremia in the elderly

45 % of Na is present in bone

Initial evaluation

History & Physical Medicines Past medical history ? Prior pituitary surgery ROS. Symptoms attributable to actue or chronic

hypernatremia Symptoms suggestive of cause. ? Dirrhea,

vomiting Chronicity acute vs chronic (>48 hours)

Examination Hypovolemia? JVP, orthostatic changes Hypervolemia? JVP, edema, chest examination

Initial lab evaluation

Plasma osmolality Low – true hyponatremia Normal or elevated: Psuedo hyponatremia, renal

failure translocational Urine osmolality

< 100 mosm/kg primary polydipsia > 100 mosm/kg reduced water excretion

Urinary sodium < 20 meq/l: decreased effective volume > 20 meq/l: “euvolemic” causes or renal Na

wasting

Further testing in hyponatremia

TSH - hypothyroid Random cortisol – primary or

secondary adrenal insufficiency Cosyntrophin stimulation test for

primary adrenal failure Chest Xray- Chest CT – lung

malignancy CT head brain, sinuses. Nasal cavity

Types of hyponatremia

Hypervolemic Hypolemic Pseudo Translocational Hyponatremia hyponatremia hyponatremia hyponatremia

Normal Euvolemic Hyponatremia

HYPOTONIC ISOTONIC HYPERTONIC

Isotonic Hyponatremia (Pseudo hypo/hypernatremia)

152 meq/lIn 850 ml

= 129

Serum proteinslipids

Serum water

15 G/L:150 ml

Measured osmolality> than calculatedosmolality

8 G/L: 80 ml

152 meq/lIn 920 ml

=140

4 G/L: 40 ml

152 meq/lIn 960 ml

=146

Approach to Hyponatremia

Serum sodium < 135 meq/l

Plasma osmolality

Normal Low High280-295 <280 >295Isotonic Hypotonic HypertenonicHyperlipidemias TranslocationalParaproteinemias Hyperglycemia Mannitol therapy

- CSWS

Urinary sodium urinary sodium

> 20 meq/l < 10 meq/l > 20 meq/l < 10 meq/l

Renal sod loss External sodium loss

- Diuretics- Osmotic diuretic - RTA with bicarbonate loss- Generation phase of metabolic alkalosis- Salt loosing nephropathies

- Skin loss- GIT

- Renal failure - CHF - Cirrhosis - Nephrotic syndrome

Hypotonic hyponatremia

Normal ECFV

Urine osmolality

<100 mosm/l >300 mosm/l

Excessive water intakeLow solute intake

Approach to Hyponatremia

SIADH Reset osmostat Endocrinopathies Potassium depletion- Drugs - Hypothyroidism - diuretic use- Tumors - glucocorticoid deficiency- CNS disorders- Nauseas- Pain- Stress- others

Treatment of Hyponatremia

Evaluation of Patient's volume status Duration and magnitude of the

hyponatremia Degree and severity of clinical

symptoms

Treatment of Hyponatremia

Hypovolemic hyponatremia: Isotonic saline to replace the contracted intravascular volume

Hypervolemic hyponatremia: Salt and fluid restriction, Loop diuretics, Correction of the underlying condition. The use of a V2 receptor antagonist may be

considered (Conivaptans iv. Tolvaptans)

Normovolemic (euvolemic), hyponatremica

Asymptomatic patients Free water restriction (< 1 L/d)

Patients with overtly symptomatic hyponatremia (eg, seizures, severe neurological deficits), Hypertonic (3%) saline Loop diuretics Water restriction

Rate of correction Acute Hyponatremia

Increase the serum sodium level by 1-2 mEq/L/h for 3-4 hours, until the neurologic symptoms subside or until plasma Na is over 120 mEq/L

Chronic, severe symptomatic hyponatremia, The rate of correction 0.5-1 mEq/L/h, with a total

increase not to exceed 8-12 mEq/L/d and no more than 18 mEq/L in the first 48 h.

Correct the hyponatremia to a safe range (usually to no greater than 120 mEq/L) rather than to a normal value.

SIADH

Essential features

• Decreased effective serum osmolality (<275 mOsm/kg)

• Urinary osmolality >100 mOsm/kg during hypotonicity of the serum

• Clinical euvolaemia

• Urinary sodium >40 mmol/L with normal dietary salt intake

• Normal thyroid and adrenal function

• No recent use of diuretics

Supplemental features

• Serum uric acid <4 mg/dL

• Serum urea <3 mg/dl• low normal serum creatinine• Fractional sodium excretion >1%,

fractional urea excretion >55%• Failure to correct hyponatraemia

after 0.9% saline infusion• Correction of hyponatraemia

through fluid restriction

• Abnormal water loading test (excretion <80% of a 20 mL/kg water load in 4 h)

• Elevated vasopressin levels despite hypotonicity and clinical euvolaemia ??

CSWS vs SIADH

Symptoms CSWS SIADH

BP Orthostatic hypotension

Normal

CVP Decreased Elevated

Heart rate Tachycardia Tachycardia

Serum osmolality

Low Low

Serum uric acid High Low

Urinary Sodium High High

Urine volume High High

Weight Decreased Increased

SIADH vs CSWHyponatremia

(No edema, no asities)

Urinary Sodium > 20 meq/l

CVP measurement

< 6 cm H2O > 6 cm H2O

CSWS SIADH

Fluid replacement Fluid restriction

Treatment of SIADH

Fluid restriction Treatment of cause Hypertonic saline plus loop

diuretics Demeclocycline Aquaretics: Conivaptans,

tolvaptans

Case A 62-year-old long-term cigarette smoking

man was noted to have a serum sodium of 129 mEq/L on a routine examination and was completely asymptomatic.

Past Hx. Prostate cancer treated by radical

prostatectomy without recurrence Physical examination; in no distress,

examination was unremarkable.

Past medical records; Serum Na in range of 129-134 and urine osmolality was consistently greater than the serum osmolality and was as high as 938 mOsmol/kg water.

An extensive workup: thyroid function test, plasma cortisol, prostate-specific antigen test, abdomen and chest computed tomography, colonoscopy, bronchoscopy, and brain magnetic resonance imaging all unrevealing.

A 1.5-L water-loading test was carried out, with results shown in Table .

Vasopressin level undetectable

Which of the following statements regarding water-loading test is correct?

A. Total urine output in 4 hours in this patient is 10% below expected amount in normal individuals

B. The water-loading test is most compatible with a diagnosis of the nephrogenic syndrome of inappropriate antidiuretic hormone secretion (NSIAD)

C. The water-loading test is compatible with reset osmostat

D. The significant decrease in urine osmolality is against a diagnosis of SIADH

Response to changes in serum osmolality

1% serum osmolality ~ vasopressin1 ng/l Urine osm 200 mosm

Ewout J. Hoorn et al. NDT Plus 2009;2:iii5-iii11

A. Unregulated secretion of vasopressin

B. Raised basal level of vasopressin

C. Reset osmostatD. Undetectable vasopressin

level gain of function mutation of V2 recepter

Types of SIADH

260 270 280 290 300

Action of ADH

Case A 69-year-old man is admitted with

increased confusion, eating poorly and still taking in water. He was taking lithium because of bipolar disorder, with nephrogenic diabetes insipidus

An elderly man in no distress, disoriented to time and place.

Afebrile, BP 83/34 mmHg, heart rate 101 beats per minute, temperature 36C, and O2 saturation 99% on room air.

Lab results

The patient received 2 L of normal saline solution. Urine volume rose to 400 ml after 12 hours and 126 mEq/L in 24 hours, with urine studies of Na 8, mEq/L, K ,4.6 mEq/L, and osmolality 70 mOsm/kg

Na 106meq/lK 4.0 meq/lCl 71 meq/lBUN 25 mg/dlGlucose 126 mg/dl

BUN 25 mg/dlCreatinine 1.1mg/dlBaseline Cr 0.9UNa 10 meq/lUK 17 meq/lOsmolality 184 mosm/kg

How much of the urine excreted at this time is made up of electrolyte-free water (CeH2O)?

A. 90% of urine output is CeH2O

B. 73% of the urine is CeH2O

C. CeH2O cannot be calculated without measurement of anions in the urine

D. CeH2O cannot be calculated without measuring a simultaneous serum osmolality

CeH2O

CeH2O = V (1 - )UNa + UKSerum sodium

= 400 (1 - )8+4.6126

= 400 ( 1-0.1) =400*0.9 =36090 % of 400

Which of the following is the best way to treat this patient at this time?

A. Increase D5W to 110% of urinary loss per hour

B. Use desmopressin and continue with D5W with goal of decreasing serum sodium to 112 mEq/L

C. Use desmopressin and continue with D5W with the goal of stabilizing serum sodium at 120 mEq/L

D. Desmopressin alone is adequate because he is nowasymptomatic

Case

A 49-year-old woman with no previous medical history completed 42-km run in 5 hours in a marathon. During the race, she consumed mineral water and ate several energy bars. Four hours after finishing the marathon, she felt dizzy, nauseous, and extremely weak, and vomited three times. Subsequently, she became disoriented and confused and was brought to the emergency room 7 hours after her symptoms began.

On admission, she was conscious but disoriented and obtunded, Her body weight 3.4 kg above her normal weight. She was afebrile and vital signs were normal. The neurologic examination showed no focal findings and plantar reflexes were flexor.

Laboratory data

Serum Na 121meq/l Serum K, 3.3meq/l Serum Cl 88 meq/l Serum HCO3 18 mol/l Uric acid 3.6 mg/dlBUN 8 mg/dlCreatinine 0.8 mg/dlGlucose 153 mg/dl

Plasma osmolality, 260 urine osmolality 489 mOsm/kgUrine Na 86 mg/dlUrine K, 75 mmol/L

SNa meq/l

IV fluids

Time hrs

Urine in ml

0 3

750 ml NSS

Tonic/clonicConvulsionsIV clonazepam

118 hrs

2.5 L NSS

121 128 136

15 18

3% SS 50 cc/h200 cc

1000 1900 750 ml

121

SNa meq/l

IV fluids

Time hrs

Urine in ml

0 3

750 ml NSS

Convulsions ?

118 hrs

2.5 L NSS

121 128 136

15 18

3% SS 50 cc/h200 cc

1000 1900 750 ml

121

Why did she develop hyponatremia?A.She lost salt and water due to sweating, replaced with free waterB.Because of candies , she had hyperglycemia osmotic diuresis, sodium lossC.Because of hyperglycemia she had translocational hyponatremiaD.She had SIADH

Why did she develop

SNa meq/l

IV fluids

Time hrs

Urine in ml

0 3

750 ml NSS

Convulsions ?

118 hrs

2.5 L NSS

121 128 136

15 18

3% SS 50 cc/h200 cc

1000 1900 750 ml

121

Why did she developA. HyperglycemiaB. HypoglycemiaC. Acute hyponatremiaD. Rapid infusion of saline

SNa meq/l

IV fluids

Time hrs

Urine in ml

0 3

750 ml NSS

118 hrs

2.5 L NSS

121 128 136

15 18

3% SS 50 cc/h200 cc

1000 1900 750 ml

121

Why her serum sodium did not improve ?SNa = [Na]inf-[Na]s

TBW+1

SNa meq/l

IV fluids

Time hrs

Urine in ml

0 3

750 ml NSS

118 hrs

2.5 L NSS

121 128 136

15 18

3% SS 50 cc/h200 cc

1000 1900 750 ml

121

SNa = [Na]inf-[Na]s

TBW+1=2.5 meq/l

Why her serum sodium improved more than expected?

Why her serum sodium increased more than expected?

Case A 55-year-old man with history of pituitary

surgery for nonfunctional pituitary macroadenoma 10 years previously. No other medical or psychiatric problems. He is admitted because of several days of anorexia, nausea, and vomiting, progressing to confusion, lethargy, and disorientation to time and place. In the emergency department, he has two generalized tonic-clonic seizures.

Inj Hydrocortisone & Isotonic saline was given. 8 hours later serum sodium improved to 115 meq/l with improvement in mental status. Dischraged 6 days later with serum sodium 131 meq/l. Returned to ER next day with tremors and difficulty speaking and swallowing. He is fully conscious and oriented with a clear sensorium, but is irritable, suspicious, and restless , pacing the halls in anger, and accusing others of talking about him and teasing him with their gestures

SNa 102 meq/l BUN5mg/dlSK 4 meq/l Creatinine 0.5 mg/dlSCl 74 meq/l U Na 78 meq/lBicarb 22 meq/l UK 50 meq/lUosm 500 mosm/kg Levels of ACTH,TSH.FSH,LH

Which one of the following statements is true about this patient?

A. Based on the patient’s symptoms, he most likely became hyponatremic because of polydipsia related to an underlying psychosis.

B. Patients presenting with a serum sodium concentration ,110 mEq/L have an expected mortality 50%.

C. The patient has pontine and extrapontine myelinolysis and his condition is likely to progress to death or to a permanent vegetative state.

D. The patient’s behavioral symptoms, tremors, and difficulty swallowing are most likely related to steroid-induced rapid correction of hyponatremia and they may resolve with time.

Points for discussion1. Prognosis of severe hyponatremia;2. Association of hyponatremia with often

unsuspected panhypopituitarism or Addison’s disease and its susceptibility to unintentional overcorrection;

3. Prevention of unintentional rapid correction of hyponatremia;

4. Pathogenesis of osmotic demyelination; 5. Hyponatremia in polydipsic patients with

psychiatric disease;6. Bbehavioral and other atypical

manifestations of pontine and extrapontine myelinolysis;

7. Prognosis of the osmotic demyelination syndrome

Prognosis of Severe Hyponatremia

Even mild hyponatremia is associated with increased mortality in both ambulatory and inpatient settings with a variety of underlying diseases, including heart failure, hepatic cirrhosis, kidney disease, critical illness, etc

Chronic hyponatremia is associated with gait disturbances, increased falls, and bone fragility and fractures in humans

Mortality due to hyponatremia

Clin J Am Soc Nephrol 6: 960–965, 2011.

at least two additional acute severe progressive illnesses, most commonly sepsis and multiorgan failure.

medication-induced hyponatremia and severe underlying illnesses uncommon

Hyponatremia with often unsuspected panhypopituitarism or Addison’s disease and its susceptibility to unintentional overcorrection

Addison’s disease.Lack of mineralcorticoids, decreased sodium reabsorption, Hypovolemia --- increased ADH secretion, decreased free water excretion- hyponatremia Treatment – Isotoinc saline

Panhypopituitarism

Decreased in ACTH, decreased cortisol Lack of Cortisol induced tonic

inhibition of ADH , Increase ADH secretion, water retention, hyponatremia

Hypersecretion of ADH may be partly due to reduced systemic BP and cardiac output or, possibly, to increased renal sensitivity to ADH.

Cortisone replacement – inhibition of ADH free water excretion,

Avoid rapid correction of hyponatremia

Prevention of excessive correction

If a water diuresis is causing the serum sodium to increase too rapidly in a chronically hyponatremic patient with a serum sodium <120 mEq/L, there are two major options: nmatch urinary water losses with 5% dextrose in water, and nadminister 2–4 ug of parenteral desmopressin to stop the water diuresis

Water deficit = TBW x ( - 1)S Na

140

Water excess = TBW x (1- )S Na

140

Electrolyte free water excretion

CeH2O = Urine volume x (1- )

UNa++UK+

S Na+CeH2O = Urine volume x ( 1- )

Blood glucose

+ U Glucose

UNa++UK+

S Na+

meq/l change in SNa after infusion of one liter= Infusate Na – S Na

TBW +1

Auto-correction of the serum sodium

The administration of saline to patients with true volume depletion.

The administration of glucocorticoids to patients with adrenal insufficiency.

Discontinuation of drugs that cause the SIADH carbamazepine, desmopressin

Discontinuation of thiazide diuretics, Spontaneous resolution of a transient cause

for SIADH (eg, surgical stress, nausea, pneumonia).

Treatment with a vasopressin receptor antagonist

ODS

Complication of treatment of hyponatremia

Too rapid correction Symptoms: headache, nausea,

vomiting, disorientation, seizures, coma, respiratory depression, death

Pathogenesis of osmotic demyelination

Chronic hyponatremia – loss of potassium, sodium, osmolytes to lower the intracellular fluid osmolality

Rapid correction –rapid entry of sodium into cell raising intracellular sodium concentration

Osmolyte

Case

74 years old women is admitted with 2 month h/o fatigue, anorexia, 6 kg weight loss. She had Chemotherapy for ovarian cancer 6 months ago. She is on hydrochlorthiazide for hypertension.

Temp 97.2OF, BP 132/75 mmHg, pulse 86/m no postural changes, no edema. Normal neurological cardiac and respiratory systems.

Which one of these is cause of hyponatremiaA. HypovolemiaB. Low solute intakeC. PseudohyponatremiaD. Primary adrenal insufficiency

Blood urea – 5 mg/dlCreatinine 0.4 mnd/dlSodium 128meq/LPotassium 3.8 meq/lChloride 90Buicarb 25Serum osm 266 mosm/Kg H2O

Urinary sodium 12 meq/lPotassium 15 meq/lOsmolality 56 mos/kgH2O

Case

An 84 years old man was admitted with fever for several days, anorexia, diarrhea and cough productive of yellow sputum

Moderate respiratory distress, BP 120/86 and pulse 74/min supine, BP 116/85, pulse 70/min on standing. Resp 24/min, temp 102oF, decreased breath sounds rt lung base

Lab reports

Blood urea – 15 mg/dlCreatinine 0.8 mnd/dlSodium 120meq/LPotassium 3.8 meq/lChloride 87Buicarb 23Glucose 320 mg/dlSerum osm 260 mosm/Kg H2O

Urinary sodium 60 meq/lPotassium 30 meq/lOsmolality 500 mos/kgH2O

Which one of these is cause of hyponatremia

A.HypovolemiaB.SIADHC.HyperglycemiaD.Low solute intake

Case

A 49 years old man presented with vomiting and diarrhea for last 3 days.

H/o smoking for > 20 years Reduced skin turgor, BP 120/75 sup,

100/55 standing. Chest examination – absent breath

sounds at left lung base, left pleural effusion and left upper lung mass on Xray

Which one of these is cause of hyponatremiaA. HypovolemiaB. Low solute intakeC. PseudohyponatremiaD. Primary adrenal insufficiency

Blood urea – 22 mg/dlCreatinine 1.0 mnd/dlSodium 114 0meq/LPotassium 3.6 meq/lChloride 96 meq/lBicarb 23 meq/lUric acid 4 meq/l

Urine sodium 6 meq/lOsmolality 498Serum osm 245 mosm/Kg H2O

Patient was treated with IV Normal saline. His serum sodium level improved to 122meq/l the next day. Saline infusion was continued, Repeat serum sodium level 120 meq/l. Repeat U Na 40 meq/l, urinary osmolality 600 mosm. Why the patient serum sodium level did not improve?

A. Pt still volume depletedB. Patient likely has underlying Addison’s diseaseC. Pt likely to have underlying SIADH

Case

A 21 years old pregnant woman was admitted to hospital at 10th week of pregnancy because of confusion restlessness after having hyperemesis for 4 weeks and loss of 3 kg weight

She was dehydrated. BP 100/70, pulse 78/minute supine and upright BP 80/65mmHg and pulse 96/minute

BloodSodium meq/l 107Potassium meq/l1.2Calcium mg/dl 9.6Mg mg/dl 1.1Phosphorus mg/dl 2.0Urea mg/dl 13Creatinine mg/dl0.9

Urine Sodium 2 meq/lPotassium 3 meq/lOsmolality 456 mosm/kg

Treatment

NSS @100 cc/hrKCL 6 meq/l

5%DW 100 cc/hrKCl 6.6 meq/l

The neurological symptoms worsened with the appearance of hypotonia, tremors and involuntary muscle spasms.

IV steroids, parental nutrition Pregnancy continued Unevenful delivery Patient able to continue her activity

with support

Hypernatremia

Pseudo hypernatremia

152 meq/lIn 920 ml

=140

152 meq/lIn 960 ml

= 146

Serum proteinslipids

Serum water

8 G/L: 80 ml 4 G/L:150 ml

Causes of Hypernatremia

A 42-year-old ultra marathon runner collapsed at the finish of the 100-mile race. She was confused and knew only her name. Blood pressure was 90/60 mmHg and pulse was 130 beats/minute; she could not stand up. No pre-marathon weight was available. Serum sodium concentration was 163 mEq/L. The most likely underlying cause of the hypernatremia is: a. Loss of hypotonic fluid across skin b. Lithium use c. Hereditary nephrogenic diabetes insipidus d. Pregnancy with increased placental vasopresinase activity e. DDAVP

A 40-year-old man with a yet undiagnosed systemic disease, including pulmonary lesions, presents with increasing thirst, polydipsia, polyuria, and a serum sodium concentrate of 152 mEq/L. Simultaneous urine osmolality was 100 mosm/kg. He takes no mediation. The most likely systemic disease responsible for the hypernatremia is: a. Diabetes mellitus b. Sarcoidosis c. Adrenal insufficiency d. Primary aldosteronism e. Hereditary nephrogenic diabetes insipidus

A 38-year-old woman with three children below the age of seven is seen by Psychiatry. A diagnosis of bipolar disease with depression is made and medication is prescribed. Four months later, she returns and states that she now is thirsty and is voiding frequently (quantitated as approximately 3.5 liters a day). Serum sodium concentration ranges from 143-145 mEq/L and BUN is 22 mg/dl. The most likely agent/process responsible for the polyuria is: a. Hypercalcemia b. Lithium c. Demeclocycline d. Sickle cell disease e. Prolonged low protein diet

An 80-year-old, partially demented man with poor nutritional status is admitted to the hospital because of pneumonia. Hyperalimentation with high protein supplementation is started (containing 30 mEq/L each of Na+ and K+). Following 5 days: Urine output: 4 L/day

BUN: 20-88 mg/dL Cr: Stable at 1.4 mg/dL [Na +]: From 140 mEq/L up to 156 mEq/L (despite a relatively high fluid intake) Posm: 342 mOsm/kg Uosm: 510 mOsm/kgUNa +: 10 mEq/LUK +: 42 mEq/L.

The free-water clearance is calculated as follows:cH2O = V x (1- )

cH2O = 4 x ( 1 - [510 ÷ 342] ) = -2 L/day

By this calculation, taking all osmoles into account, the patient retains 2 liters of water, improving hypernatremia; however, he is actually getting worse.

U osmS osm

Electrolyte free-water clearance

eCH2O = 4 (1 - [(10 + 41) ÷ 156] ) = 2.7 L/day

The patient is losing approximately 2.7 L of free water per day in his urine, likely secondary to osmotic urea diuresis caused by hyperalimentation

UNa++UK+

S Na+eCH2O = Urine volume x (1- ) + Blood glucose + U Glucose

UNa++UK+

S Na+eCH2O = Urine volume x (1- )

Treatment of Hypernatremia

Symptomatic hypernatremia Establish documented onset (acute, < 24 h;

chronic >24h) Acute hypernatremia,

Correction of serum sodium at an initial rate of 2-3 mEq/L/h (for 2-3 h) (maximum Total, 12 mEq/L/d).

Serum and urine electrolytes every 1-2 hours Serial neurologic examinations and decrease the

rate of correction with improvement in symptoms

Treatment of Hypernatremia

Chronic hypernatremia with no or mild symptoms Correction at a rate not to exceed 0.5

mEq/L/h and a total of 8-10 mEq/d (eg, 160 mEq/L to 152 mEq/L in 24 h).

If a volume deficit and hypernatremia are present, intravascular volume should be restored with isotonic sodium chloride prior to free-water administration

Calculation of Water Deficit

Water Deficit =(Plasma Sodium-140)

140X TBW

• Ongoing losses (insensible, renal) need to be added.

• Hypernatremia with volume overload (heart failure and pulmonary edema) may require diuretics or dialysis for correction.

In case of sodium and water deficit

Approach to hypernatremia

Determine volume status Calculate water deficit

Water deficit = TBWx( -1) Choose replacement fluid Determine rate of repletion

[Na+]s = after one liter

Total fluid required =

Serum Sodium140

[Na+]infus -[Na+]s

TBW +1Net S Na change

[Na+]sAfter 1 liter

Calculation of Na deficit

Deficit in mmols = 0.6x BW [Target Na- sNa]

Hypertonic saline 3% = 513 meq/l sodiumVolume of 3 % saline required in liters=Sodium deficit 500Rule of thumb; for each 1 meq/l requires

~ 70 ml hypertonic saline

Determine ongoing insensible losses

Determine ongoing sensible losses Urine out put =C electrolytes +C electrolyte

free

CeH2O = V X ( 1 - )

Determine the cause if possible

UNa++ UK+

PNa+

Treatment of Hypernatremia

Treatment of the underlying cause Free access to water Better control of diabetes mellitus. In

addition, correction of hypokalemia and hypercalcemia

Treatment for nephrogenic diabetes insipidus may be required.

Vasopressin (AVP, DDAVP) for the treatment of central diabetes insipidus.

A 45-year-old man developed hypernatremia after several days in the surgical intensive care unit, during which he received enteral nutrition without sufficient free water. At this point you are asked to provide a prescription for correcting his free water deficit assuming no ongoing losses. His weight is 70 kg. His serum sodium is 155 mEq/L. He has no edema. Restoring his serum sodium to 140 mEq/L will require which ONE of the following prescriptions?A. 6.5 L of free waterB. 2.5 L of free waterC. 4.5 L of free waterD. 8.5 L of free water

A 76-year-old man is sent to the hospital from his nursing home because of obtundation, decreased skin turgor, fever and a blood pressure of 140/80 mmHg. The serum sodium concentration is 168 mEq/L (it was 142 mEq/L four months earlier). The most likely cause of the hypernatremia is: A.Primary hypodipsia B.Prolonged low protein diet C.Hypercalcemia D.Inadequate solute-free water replacement for cutaneous pure water loss E.Lithium

The treatment goal for this patient is: A.Reduce serum sodium concentration to normal in first 12 hours B.Reduce serum sodium concentration to normal in 24 hours C.Reduce serum sodium concentration to 150 mEq/L in 24 hours D.Maintain serum sodium concentration at 165 mEq/L for first 8 hoursE.Reduce serum sodium concentration by 10 mEq/L in 24 hours

Case

A 55-year-old male diagnosed with schizophrenia was started on antipsychotic drugs 23 years back. His usual water intake 8-10 liters / days. He was having dizziness and calf cramps off and on. Now admitted for weakness of legs with serum sodium of 116 meq/l

To increase the osmolality, 5% hypertonic salinewas infused intravenously at a regular rate (0.1 mlper kilogram per minute) for 120 minutes usinga constant-infusion pump, and blood sampleswere obtained before loading, and at 30, 60, 90 and120 minutes after the beginning of loading.

oral water loading (20 ml per kilogram of body weight) was administered over a period of 15 minutes,