Sodium dreadnaught

is Hard

Joel M. Topf, MDNephrology

Sodium

Sodium is different

Most ions must be regulated because of direct effects of the ion. Arrhythmias from high (or low) potassium Weakness from high magnesium Tetany from low calcium

Sodium is not like that. The problems with high or low sodium have

little to do with direct effects of the ion. Disregulation of sodium causes changes in

cell volume.

Osmosis: the thought experiment

The movement of water in the body

The movement of water into and out of cells is analogous to the beaker experiment:

intracellular compartment extracellular compartment

When tonicity outside of the cells increases, cells shrivel.

If the concentration of solute in the cells increases the result is predictable:

The movement of water in the body

When the tonicity inside of cells increases, cells swell.

Why we care about osmolality

Alterations in cell size disrupt tissue function.

So what about sodium?

In the dark ages of medicine (50’s – 60’s) Scientists had discovered the importance

of osmoregulation but could not reliably measure osmolality.

However, flame photometry allowed reliable sodium measurements.

Changes in sodium roughly paralleled changes in tonicity.

Sodium is an indicator of osmolality

The clinically important variable is tonicity. We are interested in sodium because it gives a

good clue to the tonicity. This is analogous to taking patients temperature: We are interested in whether the patient has

an infection. There are better tests for infection but none

as convenient as sticking a thermometer in the mouth.

There are better tests of tonicity than serum sodium but none as clinically convenient.

Tonicity versus Osmolality

Osmolality Total concentration

of all particles in solution.

Tonicity Concentration of

only the osmotically active particles.

Only impermeable particles contribute to tonicity.

Only impermeable particles cause changes in cell volume.

Summary

We are interested in plasma tonicity because: When elevated, water leaves the cells

causing dysfunction. When decreased water moves into the

cells causing dysfunction. We are interested in sodium because

it usually tells us the plasma tonicity.

Low sodium: hyponatremia

Hyponatremia is defined as a sodium concentration less than 135 mEq/L. Pseudohyponatremia is when the

sodium concentration is low (< 135) but osmolality is high or normal.

True hyponatremia is when both the sodium and the osmolality are low.

Pseudohyponatremia: high osmolality

Elevated glucose (or mannitol) raise plasma tonicity which draws water from the intracellular compartment diluting plasma sodium.

Hillier TA, Abbott RD, Barrett EJ. Am J Med 1999; 106: 399-403.

Pseudohyponatremia: high osmolality

Correcting the sodium for hyperglycemia. Traditional Katz conversion

Add 1.6 to the sodium for every 100 mg/dL the glucose is over 100.

Example: Na = 126 mEq/L. Glucose = 600 mg/dL: 600 - 100 = 500. So the glucose is five 100’s over 100 5 x 1.6 = 8 126 + 8 =134 True sodium equals 134 mEq/L To remember 1.6 think “Sweet 16”

Hillier TA, Abbott RD, Barrett EJ. Am J Med 1999; 106: 399-403.

Pseudohyponatremia: high osmolality The only study on this

was conducted by Hillier and published in 1999. N=6 Somatstatin infusion

prevents endogenous insulin release.

D20 0.45 NaCl infused to raise glucose > 600 mg/dL.

An insulin gtt then gradually lowers glucose to 140 mg/dL.

Glucose and Na measured every 10 minutes.

Hillier Study on Pseudohyponatremia

Na = 140 - 0.016 Glucose

Na = 140 - 0.024 Glucose

Na = 141 - 0.016 Glucose

Na = 151 - 0.04 Glucose

Pseudohyponatremia: high osmolality Conclusion: sodium has a

biphasic relationship to glucose. Serum Glucose less than

400 use 1.6 mg per 100mg/dL conversion.

For glucose over 400 use 4.0 per 100mg/dL.

Alternatively you can 2.4 per 100 mg/dL.

Example: Na = 126 mEq/L. Glucose = 600 mg/dL: Using the biphasic

relationship: From 100 to 400 the

change is 1.6 x 3 = 4.8 From 400 to 600 the

change is 4.0 x 2 = 8 4.8 + 8 = 12.8 126 + 12.8 = 149

mEq/L Using the simple

relationship From 100 to 600 the

change is 2.4 x 5 = 12 126 + 12 =148 mEq/L

Compare this to the Katz conversion of 134 mEq/L

Pseudohyponatremia: Normal osmolality Increased protein or lipids can cause a lab error

causing a falsely lowered sodium. Hyperlipidemia Hypercholesterolemia TPN with lipids IV immunoglobulin

infusions

Susceptible Flame photometry Indirect- potentiometry

Over 66% of clinical labs

Not Susceptible Direct potentiometry

ABG laboratories Participant summary report: surveys 1982-2002. Northfield, Ill.:

College of American Pathologists, 1982-2002.

True hyponatremia

Hyponatremia occurs when water intake exceeds water excretion.

True hyponatremia

Hyponatremia does not occur when sodium excretion exceeds sodium intake.

Negative salt balance causes hypovolemia

If a person drinks more water than the kidney is capable of clearing the excess water will dilute the plasma.

Causes of hyponatremia: Increased intake

To exceed the maximal renal clearance of water an adult needs to drink about 18 liters a day.

clearing

Water clearance

Clearance as a general concept: The clearance of any substance is the volume

of blood cleared of that substance in a set unit of time.

Water clearance Total water clearance is equal to urine output. Not a

useful concept.

€

CX =UX ×V

PX

Free water clearance and soup Imagine urine divided

into two components A solute component

containing all of the solute at the same osmolality as plasma.

Loss of this component does not change plasma osmolality

Ladle of soup A free water component

providing the balance of the volume.

Loss of this solute free water will change serum osmolality.

Boiling off water from soup

In regards to sodium all that matters is the free water component

Free water clearance

0.5 liter free water

1 liter 142 mOsm/Kg

0.5 liter 284 mOsm/Kg

Solute component (plasma osmolality 284 mOsm/kg)

Use clearance to calculate the osmolar clearance

€

Cosm =Uosm ×V

Posm

€

Cosm =142 ×1

284

€

Cosm = 0.5


1 liter 142 mOsm/Kg


Solute component (Solute Clearance)

??0.5 liter Zero mOsm/Kg

Free water component (Free water Clearance)The free water

component equals urine volume minus the solute component



1 liter 284 mOsm/Kg

-0.5 liter 568 mOsm/Kg


1 liter 284 mOsm/Kg


Solute component (plasma osmolality 284 mOsm/kg)

Use clearance to calculate the osmolar clearance

€

Cosm =Uosm ×V

Posm

€

Cosm =568 × 0.5

284

€

Cosm =1.0


Solute component (Solute Clearance)

??Free water component (Free water Clearance)


– 0.5 liter Zero mOsm/Kg

1 liter 284 mOsm/Kg

Free water clearance: Implications

Dilute urine Solute free water

Dilute urine increases serum osmolality

Concentrated urine Negative free water

Concentrated urine de-creases serum osmolality

Na+

Na+

€

CtH2O=V

CtH2O=Cosm +CH2O

Substitute V for CtH2O

V =Cosm +CH2O

CH2O=V −Cosm

CH2O=V −

Uosm ×V

Posm

⎡

⎣ ⎢

⎤

⎦ ⎥

CH2O=V × 1−

Uosm

Posm

⎡

⎣ ⎢

⎤

⎦ ⎥

Free water clearance: The math

Free water clearance: Math Examples

€

CH2O=V × 1−

Uosm

Posm

⎡

⎣ ⎢

⎤

⎦ ⎥

CH2O=1000 × 1−

50

285

⎡ ⎣ ⎢

⎤ ⎦ ⎥

CH2O= 825ml

€

CH2O=V × 1−

Uosm

Posm

⎡

⎣ ⎢

⎤

⎦ ⎥

CH2O=1000 × 1−

1200

285

⎡ ⎣ ⎢

⎤ ⎦ ⎥

CH2O= −3211ml

Electrolyte free water clearance

Osmolality doesn’t cause problems, rather tonicity causes changes in cell volume which cause clinical syndromes.

So free water clearance must be refined to measure clinically significant changes in tonicity.


Osmotically active particles (those that contribute to tonicity): Sodium Potassium Albumin, calcium and others

Sodium is the dominant osmotically active solute of serum to the point that others can be ignored.

Urine has a significant potassium content so in urine sodium and potassium are equal partners in determining urinary tonicity.


Convert the free water clearance calculation to electrolyte free water clearance Substitute urine osmolality with the sum urine

Na + K Substitute serum osmolality with serum sodium

€

CH2O=V × 1−

Uosm

Posm

⎡

⎣ ⎢

⎤

⎦ ⎥


€

CEFW =V × 1−UNa +UK

PNa

⎡

⎣ ⎢

⎤

⎦ ⎥


Electrolyte free water clearance: CHF vs. SIADH Heart Failure

Urine Osmolality: 800 Serum Osmolality: 270 Urine Volume: 800 Urine Na: 5 Urine K: 40 Serum Na: 125

SIADH Urine Osmolality: 800 Serum Osmolality: 270 Urine Volume: 800 Urine Na: 125 Urine K: 40 Serum Na: 125

€

CH2O=V × 1−

Uosm

Posm

⎡

⎣ ⎢

⎤

⎦ ⎥

CH2O= 800 × 1−

800

270

⎡ ⎣ ⎢

⎤ ⎦ ⎥

CH2O= −1570ml

€

CH2O=V × 1−

Uosm

Posm

⎡

⎣ ⎢

⎤

⎦ ⎥

CH2O= 800 × 1−

800

270

⎡ ⎣ ⎢

⎤ ⎦ ⎥

CH2O= −1570ml

€


PNa

⎡

⎣ ⎢

⎤

⎦ ⎥

CEFW = 800 × 1−5 + 40

125

⎡ ⎣ ⎢

⎤ ⎦ ⎥

CEFW = 512

€


PNa

⎡

⎣ ⎢

⎤

⎦ ⎥

CEFW = 800 × 1−125 + 40

125

⎡ ⎣ ⎢

⎤ ⎦ ⎥

CEFW = −256

Etiology of hyponatremia

Hyponatremia occurs when water intake exceeds water excretion.

Hyponatremia occurs when water intake exceeds electrolyte free water clearance.

Ingestion > EFW clearance

Etiology of hyponatremia

Previously stated that the kidney is able to clear 18 liters of water a day

Hyponatremia routinely occurs with water intake less than 2 liters

So something must prevent the full free water clearance

Dilute urine Solute free water

Hyponatremia is primarily due to an inability to produce

dilute urine

Etiology of Hyponatremia: 3 steps to generating dilute urine

1.Delivery of water to the diluting segments of the nephron.

2.Functional diluting segments.

3.Collecting tubule impermeable to water (lack of ADH)

1400

285

100 50

Failure to Generate dilute urine

Lack of water delivery to the diluting segments. Renal failure

Volume deficiency Cirrhosis Heart failure Nephrotic syndrome


Ineffective solute reabsorption diluting segments: Thick ascending limb

of the loop of Henle (TALH)

Distal convoluted tubule.

Diuretics Non-oliguric ATN


Permeable collecting ducts (ADH) Volume related ADH SIADH

Drug induced Paraneoplastic CNS Pulmonary disease

Adrenal insufficiency Hypothyroidism

ADH is normally used to regulate osmolality

The pituitary releases ADH when osmolality rises. ADH causes the kidney to retain water

which lowers osmolality. ADH ADds Hydration to the body.

ADH is normally used to regulate osmolality

We start with an increase in the plasma osmolalityThis is detected by the brainThe brain releases ADHADH acts on the kidneyThe kidney reacts by retaining water and producing a small amount of concentrated urine.

The retained watergoes here

not here

ADH is also secreted when there is poor perfusion.

With large drops in perfusion/blood pressure (7-15%) the body uses ADH to support perfusion.

ADH aids circulating volume by decreasing the excretion of water from the kidney and causing vasoconstriction.

When this occurs the body accepts the trade-off of lowered sodium concentration to restore or maintain circulation.

SIADH: ADH release with no physiologic benefit

ADH should not be present when: The osmolality is

normal or low and Perfusion is normal.

The release of ADH under these conditions is inappropriate. Syndrome of

Inappropriate ADH (SIADH)

4 Criteria for the diagnosis of SIADH:1. Low serum Na and low

serum osmolality2. Clinically euvolemic3. Urine osmolality 200

more than serum osmolality

4. Urine sodium over 20 mmol/L

Also must have normal adrenal and thyroid axis

Causes of SIADH

MDMA (Ecstasy) Neurological:

Meningitis Tumors Trauma SAH

Pulmonary disease: Asthma Mechanical ventilation Pneumonia TB

Stress Pain Vomiting Post-surgical

Medication Antipsychotics SSRI First generation sulfonylureas Pitocin/Oxytocin Narcotics Cyclophosphamide

AIDS

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.

The response to hyponatremia

Low sodium concentration causes water to move into the cells.In the brain this causes an increase in ICP.

Compensated chronic hyponatremia is essentially

asymptomatic.

The problem with compensation

The starting point is after compensation has reduced the amount of intracellular solute and the ICPNow, an over-eager intern sees the low sodium and starts an infusion of 3% NaCl to raise the sodium to normal.

Sodium

108Sodium

134

The sodium draws water from the inside of the cells causing the brain to shrivel.

The problem with interns

Central pontine myelinolysis This brain shrinkage can

cause central pontine myelinolysis: Quadriplegia Respiratory paralysis Mental status changes Usually fatal within three to

five weeks Risk factors:

Hyponatremia for > 24 hours Over-correction of

hyponatremia (> 25 mEq/L/day)

Rapid correction (greater than 1–2 meq/hr)

Alcoholism Malnutrition Liver disease

Damned if you do. Damned if you don’t

Without treatment patients have cerebral edema.

With mistreatment patients are at risk of CPM.

QuickTime™ and aTIFF (LZW) decompressor


Symptomatic vs. Asymptromatic Uncompensated, symptomatic

hyponatremia Treat aggressively with 3% saline.

Compensated, asymptomatic hyponatremia Treat conservatively

Symptoms Mental status changes Nausea Vomitting Head ache Movement abnormalities Seizures Hypoxia/respiratory failure

Symptomatic vs. Asymptromatic

Use the etiology of hyponatremia as a clue to duration of hyponatremia Patients with which are long standing

disease processes are more likely to be chronic:

SIADH CHF Cirrhosis

Likely to cause acute hyponatremia: Psychogenic polydipsia Thiazide diuretics Post-operative hyponatremia

Symptomatic vs. Asymptromatic

The clock and calendar are unreliable measures of chronicity. The text books say compensation should

be complete by 24 to 48 hours. Ayuf and Arief would argue otherwise.

Prospectively collected case series of 53 postmenopausal women.

Average duration of hyponatremia: 5.2 days All had severe neurologic symptoms.

Ayus JC, Arieff AI. JAMA 1999; 281: 2299-2304.

Chronic or acute hyponatremia



Conservative therapy for asymptomatic hyponatremia

Do no harm. Fluid restrict the patient.

Check the urine Na and K and calculate the free water clearance.

Restrict water intake below this free water clearance (add 1 liter of insensible losses) and the sodium will rise.

0.5 mmol/L/hr No more than 12 mmol in the first day.


Take a typical patient with SIADH Urine Na 140 Urine K 40 Volume 800 mL Serum Na 115

CEFW = –452 Hard to restrict the free water to less

than zero.

Water restriction is ineffective



Cool furosemide trick Give Mr. SIADH 20

mg of furosemide BID

Makes the urine like 0.45NS.

Recheck free water clearance

SIADHUrine Na 140Urine K 40Urine Volume 800Serum Na 115Electrolyte freewater Clearance

–452

CHFUrine Na 5Urine K 40Urine Volume 800Serum Na 115Electrolyte freewater Clearance

487

SIADH +Lasix7030

2500115326

CHF +Lasix7040

2500115109


Acute symptomatic hyponatremia

In patients with neurologic symptoms due to hyponatremia: 3%.

Increase sodium until symptoms abate or 6 mmol/L, which ever comes first.

Increase Na < 25 mmol/L in the first 24 hours.

Use the change of sodium formula.

Change in sodium formula

The formula predicts serum sodium following any infusion. Works equally well

in hyponatremia and hypernatremia.

comes in two varieties: Simple General

€

ΔNa =Viv × Naiv +K iv( ) −Vu × Nau +Ku( ) − ΔV ×Nas

TBW + ΔV

⎧ ⎨ ⎩

⎫ ⎬ ⎭

€

ΔNa =Naiv +K iv −NasTBW +1

⎧ ⎨ ⎩

⎫ ⎬ ⎭

Change in sodium following one liter of any IVF.

TBW = kg x 0.7 or 0.6 or 0.5 or 0.4

Na in 3%: 513Na in 0.9%: 154Na in 0.45%: 77Na in 0.225%: 39

Change in Sodium Formula: Examples

66 yo AA female 3 days post-op from TAH develops seizures and is unresponsive. Na = 108 K = 2.8 Weight = 65 kg

Raise Na 6 mEq in 2 hours give 300 ml/hr for 2 hours or until symptoms resolve.

After that 100mL will increase serum Na by 1mmol/L.

Check frequent serum Na, recheck change in Na calc.

The speed limit is less than 25 mmol/L in first day

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⎧ ⎨ ⎩

⎫ ⎬ ⎭

ΔNa =513+ 20 −108

65 × 0.6( ) +1

⎧ ⎨ ⎩

⎫ ⎬ ⎭

ΔNa = 9.625

Hyponatremia: Summary

Hyponatremia is a sodium < 135 mEq/L Rarely, it is associated with a normal or high

osmolality and is called pseudohyponatremia. Otherwise, it is due to an imbalance in the

intake and excretion of water. It increases the icp but after 24 hours the

body compensates. Treatment of acute hyponatremia can occur

at 1.5-2.0 mEq/L per hour. Treatment of chronic hyponatremia must be

at 0.5 mEq/L per hour at the fastest.

Hypernatremia

Hypernatremia is defined as a sodium > 145 mEq/L. Hypernatremia is associated with increased hospital

mortality. Patients who present with hypernatremia typically get

appropriate therapy. In patients who develop hypernatremia while hospitalized

don’t get therapy as often.

Causes of hypernatremia Water excretion exceeds

water intake Two step process

Generation

Generation Gain of sodium Loss of water

Maintenance Maintenance

Inability to ingest water

Without both of these processes there cannot be hypernatremia.

70 kg man with Na of 140 Receives 5 amps (500 mL) of

bicarb during a code.

€


⎧ ⎨ ⎩

⎫ ⎬ ⎭

ΔNa =1000 + 0 −140

42 +1

⎧ ⎨ ⎩

⎫ ⎬ ⎭

ΔNa = 20

Generation – Gain of sodium Ingestion of

excessive sodium can generate hypernatremia. Causes of this include:

Use of 3% saline Use of bicarbonate

infusions Overdose of salt tablets

If he received a liter the Na would be 160, but with 500mL it rises to 150.

Generation – Loss of water Water losses:

Extra-renal Diarrhea Vomiting Losses through the skin

with burns Renal losses

Osmotic diuresis Hyperglycemia Mannitol Post-obstructive Post-ATN (diuretic

phase) Diabetes insipidis

Renal losses are cases of high electrolyte free water clearance

€


PNa

⎡

⎣ ⎢

⎤

⎦ ⎥


Diabetes insipidis

Diabetes insipidus generates hypernatremia by allowing large renal water losses.

Diabetes insipidus is due to the lack of ADH activity. Central diabetes insipidus: ADH is not being released.

Nephrogenic diabetes insipidus: End organ (kidney) resistance to ADH

Diabetes insipidis

Central CNS disease

Neurosurgery Pituitary disease Tumor Infiltrative disease Autoimmune/

idiopathic Pregnancy

Nephrogenic Lithium Demeclocycline Congenital Hypokalemia Hypercalcemia Sickle cell disease Sjorgrean’s

syndrome

Maintenance of hypernatremia

The body rapidly corrects hypernatremia following generation by ingesting water.



Inability to drink



For hypernatremia to persist there must be an inability to drink: No water available Too small to express thirst: Babies Unconscious/mental status changes Vomiting On tube or IV feedings with an

inadequate amount of water

Inability to drink

For hypernatremia to persist there must be an inability to drink: No water available Too small to express thirst: Babies Unconscious/mental status changes Vomiting On tube or IV feedings with an

inadequate amount of water

Summary of hypernatremia

Generation Addition of sodium

IV Bicarbonate Salt in formula Salt tablet ingestion

Loss of water Vomiting Diarrhea Skin losses Diabetes insipidus Osmotic diuresis

Maintenance Inability to drink water

No water available Too small to get water Mental status changes Improper TPN or tube

feedings

Hypernatremia is a sodium concentration > 145 mEq/LThe development of hypernatremia is a two part processes:

Consequences and compensation

Symptoms of hypernatremia

The movement of water from the brain cells causes the brain to shrink. This can cause rupture of the cerebral veins

leading to intracerebral and subarachnoid hemorrhages.

Symptoms begin with lethargy, weakness and irritability.

Worsening disease is characterized by twitching, seizures and coma.

Insulin resistance and hyperglycemia

Consequences of mismanagement

This compensation prevents rapid treatment of chronic hypernatremia, just as with low sodium.

Treatment

Provide electrolyte free water to disrupt the maintenance of hypernatremia Enteral water is preferred D5W results in hyperglycemia

Note on D5W, since D5W distributes through the total body water 1 liter of D5W increases the intravascular space by only 83 mL

Use the change in sodium formula to calculate the fluid volume.

The amount of fluid

TBW= kg x % body water 0.6 for well hydrated

males 0.5 for well hydrated

females reduce by 0.1 for:

Obesity Elderly Dehydration

€

Initial Na =168 mmol/L


ΔNa =0 + 0 −168

42 +1ΔNa = 3.9 ≈ 4

Each liter of D5 or free water lowers Na 4, so 6 liters will reduce the Na to 144.

The rate of correction

There are two speed limits for correction Chronic asymptomatic should be

corrected no faster than 0.5 mmol/L per hour.

Acute symptomatic hypernatremia can be corrected at 1.0 mmol/L per hour.

Using the prior example of 6 liters to correct 24 mmol, give that volume over 24 hours for acute hypernatremia: 250 mL/hr.

Accounting for ongoing losses

Patients with NDI have large ongoing free water losses (200-300 mL/hr).

Failing to account for these losses will result in a failure to correct the hypernatremia. Patient in the recovery phase of ATN may

make 300mL/hr calculating the CEFW will reveal ongoing losses of 150 mL of EFW.

Add 150 to the calculated rate. 250 + 150 = 400 mL/hr.

Treating hypernatremic patients

Some tid-bits about treating these patients: Many of these patients have poor

perfusion or early stage shock. Treat shock and compromised perfusion

as you would with a normal sodium. After perfusion is restored treat the

hypernatremia.

Hypernatremia summary

Hypernatremia is defined as a sodium > 145. There are always two processes causing

hypernatremia: Generation: ingestion of sodium or loss of water. Maintenance: Inability to drink water.

Symptoms are primarily neurologic from the decrease in cell volume in the brain.

The brain compensates for this loss of volume by adding solutes inside the cells.

Sodium dreadnaught

Health & Medicine

Transcript of Sodium dreadnaught