Sodium Imbalances: Hyponatremia and Hypernatremia

Sodium Imbalances

Sodium

• Sodium is represented by the symbol Na.
• A joke: I was going to make a joke about sodium, but… Na.

Sodium Distribution

• More than 95% of the body's sodium is found in the extracellular fluid (ECF).
• Sodium is the most plentiful electrolyte in the ECF compartment.
• Sodium concentration is very low in the intracellular fluid (ICF).
• The sodium-potassium pump maintains this asymmetrical distribution.

Normal Sodium Levels

• Normal sodium levels: $135 – 145 \, \text{mEq/L}$
• Hyponatremia: lower than $135 \, \text{mEq/L}$.
• Hypernatremia: higher than $145 \, \text{mEq/L}$.
• These values need to be memorized.

Sodium's Primary Role

• Regulating water distribution.
• A loss or gain of sodium comes with a loss or gain of water.

Sodium Effect on Body Cells

• Low serum sodium (Hyponatremia): diluted ECF, water drawn into cells.
• High serum sodium (Hypernatremia): concentrated ECF, water pulled out of cells.

Dietary Sodium

• A healthy person can maintain sodium balance over a wide range of intake as the kidneys can conserve or excrete sodium as needed.
• A sodium intake of $1.5 \, \text{g}$
  per day is adequate for healthy individuals who are not losing sodium excessively.

Hyponatremia (Low Sodium Level)

• A serum sodium level < 135 \, \text{mEq/L}.
• The most frequent electrolyte disorder in hospitalized patients.
• A low serum sodium concentration does not necessarily mean that the total body sodium is less than normal.
• Two types of Hyponatremia:
  • Dilutional hyponatremia: due to excess water gain.
  • Depletional hyponatremia: due to excessive sodium loss.

Hyponatremia – Incidence

• Approximately 2.5% of hospitalized patients have hyponatremia.
• In critical care patients, incidence is up to 15%.
• Mortality rate in hospitalized patients with hyponatremia is approximately 30% - 40%, reflecting the severity of the underlying disease process, not the hyponatremia itself.

Hyponatremia - Pathophysiology

• Acute hyponatremia: developed in less than 48 hours.
• Chronic hyponatremia: present for more than 48 hours.

Hyponatremia – Pathophysiology: Causes

1. Loss of sodium:
   • Through the kidney
   • GI tract
   • Skin
2. Gain of water:
   • Excessive water intake
   • High ADH secretion
3. Edematous states:
   • CHF (Congestive Heart Failure)
   • Cirrhosis
   • Nephrotic syndrome
4. Shift of water from the cell to the ECF, as in hyperglycemia. Sodium level can drop by $2 \,\text{mg/dL}$
   for each $100 \,\text{mg/dL}$
   of glucose.

Hyponatremia Severity

• Can range from mild to severe.
• When severe, it is often a marker of a serious underlying disease.
• Severe hyponatremia can cause neurological symptoms.

Hyponatremia and Fluid Situations

1. Hyponatremia with ECF volume excess (FVE)
2. Hyponatremia with ECF volume deficit (FVD)
3. Hyponatremia with normal ECF volume

Cellular Swelling & Hyponatremic Encephalopathy

• Encephalopathy: a group of conditions that cause brain dysfunction.
• A decrease in sodium concentration causes a shift of water from the ECF to the intracellular space, resulting in cellular edema.
• The brain's capacity to expand is limited by the skull unlike other tissues.

Brain Edema

• Increased Intra-Cranial Pressure (ICP) (לחץ תוך גולגולתי גבוה)
• Herniation and death or irreversible brain damage

Herniation

• When something is pushed out of its normal place because of pressure or weakness.
• Brain Herniation: due to swelling or bleeding, brain tissue can get pushed down through openings like the foramen magnum.
• This can be fatal.

Brain's Protective Mechanism (NAKPase system)

• When the brain starts swelling, its cells activate the sodium-potassium pump to push sodium out of the cells.
• This helps stop water from entering and making the swelling worse.

Hyponatremia - Causes

• Water Intoxication
• Loss of sodium.
• Gains of water.
• Diseases associated with SIADH.
• Drugs.

Hyponatremia – Causes: Gastrointestinal Fluid Losses

• Vomiting: direct loss of gastric fluid, sodium. Hyponatremia from vomiting will not be severe unless there is an excessive intake of only water.
• Diarrhea: loss of intestinal fluid.

Hyponatremia – Causes: Excessive Release of Antidiuretic Hormone

• SIADH (syndrome of inappropriate antidiuretic hormone secretion) is associated with excessive water retention, and therefore dilutional hyponatremia.
• Diseases associated with SIADH (no need to remember):
  • Carcinoma of lung, carcinoma of pancreas or duodenum, head trauma, stroke, pulmonary disorders, early postoperative period.

Hyponatremia – Causes: Adrenal Insufficiency

• Adrenal insufficiency = Aldosterone deficiency. (Aldosterone = keeps sodium)
• Reduced Aldosterone level causes sodium loss.

Hyponatremia – Causes: Sweating

• Sweat = a hypotonic fluid with a sodium concentration about $30 – 65 \, \text{mEq/L}$.
• (0-1000 ml range)
• During exercise in a hot, dry climate loss may be as high as $1500 \, \text{ml/hour}$.

Hyponatremia – Causes: Salt-Losing Nephritis

• Kidney diseases that cause renal excretion of salt.
• Can range from mild to severe.

Hyponatremia – Causes: Diuretics

• Diuretic induced hyponatremia is mostly common in thiazide diuretics (not loop).
• Found as a cause or top contributor to severe hyponatremia in hospitals.

Hyponatremia – Causes: Drugs

• Antidepressants – TCA, SSRI
• Antineoplastic agents – for cancer patients
• Carbamazepine – anti-seizure
• NSAIDS – for inflammation, pain, fever
• Desmopressin – for children bedwetting

Hyponatremia – Causes: Oxytocin in Pregnancy

• Oxytocin, like ADH, is synthesized in the hypothalamus and released by the pituitary gland.
• Primary effect: uterine function and milk production
• Also has some antidiuretic activity. If given improperly during labor, can result in hyponatremia.

Hyponatremia – Causes: Ecstasy (MDMA)

• "The club drug"
• Enhances the release of ADH from the hypothalamus and causes hyponatremia, which can cause neurological symptoms.

Hyponatremia – Causes: Postoperative Hyponatremia

1. Stress and anesthesia increase ADH
2. Pain causes increase in ADH
3. Nausea causes increase in ADH

Hyponatremia – Causes: Central Nervous System Disorders

• Head trauma, Neoplasms (tumors), Infections.
• This can happen due to SIADH or cerebral salt wasting (CSW).

Hyponatremia – Causes: Malignant Tumors and SIADH

• In different malignancies, cancer cells release a substance like ADH.
• Malignancies: lung cancer, pancreas, duodenum, leukemia.

Hyponatremia – Causes: Compulsive Water Drinking

• Polydipsia = drinking lots.
• Seen in psychiatric patients.
• 7% of schizophrenic patients have primary polydipsia.
• (Psychiatric drugs also cause dry mouth)

Hyponatremia – Causes: Pulmonary Disorders associated with SIADH

• Pneumonia, acute asthma, tuberculosis, acute respiratory failure, pneumothorax, empyema.
• Pathophysiology not clear.

Hyponatremia – Causes: AIDS

• Acquired Immunodeficiency Syndrome
• 56% of patients with AIDS have hyponatremia.
• AIDS is a medical condition where the immune system is too weak to fight infections.
• HIV is a virus which attacks the immune system in humans.

Hyponatremia – Causes: Endurance Exercise Hyponatremia

• Post marathon \ triathlon events. Athletes' intake water only, that does not replenish the sodium.

Hyponatremia – Clinical Signs

• Clinical signs of hyponatremia depend on the following factors:
  1. The level of the sodium decrease. The lower the sodium – the more severe the symptoms are.
  2. Speed of development (acute \ chronic): in chronic slow hyponatremia leading to cerebral edema, there is time for cerebral adaptation. The adaptation results in return of brain volume toward normal and ending of neurological symptoms. In acute hyponatremia, symptoms develop at a high rate. Patients with acute sodium decrease are in higher mortality rate than slow developing.
  3. Cause of hyponatremia: is it loss of sodium or gain of water? Acute water excess is more likely to cause severe symptoms than is the chronic loss of sodium.
  4. Age and gender differences: menstruating aged women are in greater risk for irreversible brain damage, more than men or post menopause women. Estrogen makes their brain less able to adapt to the effects of hyponatremia than are those of men or postmenopausal women.
  5. Early vs late symptoms: early manifestation include GI signs. Major symptoms are neurological, relating to brain swelling.

Hyponatremia – Clinical Manifestations

1. Nausea and vomiting
2. Abdominal cramps
3. Lethargy
4. Headache
5. Seizures
6. Respiratory arrest
7. Coma

Hyponatremia – Clinical Manifestations: Volume Status

1. Hyponatremia due to water overload (FVE) increases body weight but does not cause significant edema because approximately $\frac{2}{3}$
   of retained water is located in the cells.
2. Hyponatremia due to sodium loss is associated with ECF deficit (FVD) and symptoms of weakness and postural hypotension + dizziness

Hyponatremia – Clinical Manifestations

• Stupor/coma
• Anorexia, (nausea and vomiting)
• Lethargy
• Tendon Reflexes (decreased)
• Limp muscles (weakness)
• Orthostatic hypotension
• Seizures/headache
• Stomach cramping

Hyponatremia – Clinical Manifestations: Severity of Symptoms

1. Dilutional hyponatremia has more severe symptoms than depletion hyponatremia.
2. Acute hyponatremia has more severe symptoms than chronic or slow developing hyponatremia.
3. Women of child bearing age are at higher risk from fatal outcomes from hyponatremia (irreversible damage \ death)

Hyponatremia – Clinical Manifestations: Urinary Laboratory Data

1. Hyponatremia due to sodium loss from a non-renal route (GI), will show low urinary sodium level, indicating renal conservation of needed sodium.
2. Hyponatremia due to SIADH will show a high urinary sodium level.

SG (Specific Gravity) of Urine

Hyponatremia - Treatment

• Basic principles for treatment:
  1. Increasing the sodium concentration at a safe rate
  2. Treating the underlying cause

Hyponatremia - Treatment: Sodium Replacement

• For sodium loss hyponatremia
• If a patient can consume fluids and food – sodium can be replaced orally (PO).
• In acutely ill patients – sodium is replaced IV- with sodium containing fluids (isotonic fluids – 0.9% Normal saline \ HARTMANNS RL.)

Hyponatremia - Treatment: Water Restriction

• For water excess hyponatremia (dilutional hypo)
• In non-volemic patients with chronic asymptomatic hyponatremia, water restriction is generally recommended.
• Water restriction to less than $1 \backslash 1.5$
  L is usually successful in reversing hyponatremia between $125 –135 \, \text{mEq/L}$,

Hyponatremia - Treatment: Hypertonic Saline and Loop Diuretics

• For hyponatremia with neurologic symptoms
  1. Hypertonic saline should be administered only in ICU for close monitoring
  2. Only with use of an IVAC (volumetric pump) to provide precise flow rate.
  3. Frequent monitoring of plasma sodium levels
  4. Monitor for fluid volume excess, especially in cardiac patients
  5. Monitor for worsening of neurological signs (can signal CPM – central pontine myelinolysis – when sodium is corrected too fast)
  6. In acute hyponatremia- increase the sodium levels by $1.5-2 \, \text{mEq/L}$
     for the first 3-4 hours because the risks are high. The total increase should not be greater then $10-12 \, \text{mEq/L}$
     over the first 24 hours.

Hyponatremia - Treatment: Complication of Rapid Correction

• CPM = Central Pontine Myelinolysis
• The goal of treatment in symptomatic hyponatremia is to:
  1. reduce brain swelling (due to entry of water)
  2. increase the plasma sodium level only to the point needed for normal respiration
  3. keep patient alert and seizure free.
• All this, while preventing CPM.
• CPM = a result from shrinkage of neurons away from their myelin sheaths, due to water shifts associated with rapid correction of hyponatremia.
• Greatest risk for CPM = when sodium is corrected by more than $12 \, \text{mEq/L}$
  in a 24 hour period.
• In symptomatic hyponatremia where patients are experiencing seizures \ acute neurological symptoms - sodium correction would be quicker since the risk of neurological damage \ death is higher.
• In an asymptomatic patient, an increase in $0.5 \, \text{mEq/L \ hour}$
  (and less than $10 \, \text{mEq/L}$
  the first day)

Hyponatremia - Treatment: Arginine Vasopressin Receptor Antagonists

• For dilutional hyponatremia due to SIADH (excessive ADH activity)
• AVP receptor antagonists – shown to normalize serum concentration by causing water diuresis.

Hypernatremia

• A serum sodium above normal > $145 \, \text{mEq/L}$

Hypernatremia - Causes

• Water Deprivation (not getting enough water)
• Breastfeeding associated hypernatremia
• Watery diarrhea
• Insensible water loss
• Excessive sodium intake
• Diabetes insipidus

Hypernatremia - Causes: Water Deprivation

• May occur in any patient with a decreased mental status who is not able to respond to Thirst.
• Hypernatremia is most often seen in patients who are 65 or older.
• Older patients are associated with:
  • Decreased thirst mechanism
  • Decreased ability of the kidneys to conserve water in times of need.
• Infants are also at risk because they are unable to ask for water.

Hypernatremia - Causes: Breastfeeding Associated Hypernatremia

• Hypernatremic dehydration in breast feeding neonates can be due to either
  • High level of sodium in breastmilk
  • Inadequate lactation.
• This can be a life-threatening condition.

Hypernatremia - Causes: Watery Diarrhea

• Leading cause for hypernatremia in children, especially when the water intake is decreased due to nausea.
• Other causes of hypernatremia in children:
  • Fever (increased insensible water loss)
  • Excessive sodium administration

Hypernatremia - Causes: Insensible Water Loss

• Loss via Respiration + loss via evaporation from the Skin = $1000 \, \text{ml}$
  of water per day, in a normal and healthy adult.
• In any increase of these losses – a greater risk for hypernatremia.

Hypernatremia - Causes: Excessive Sodium Intake

• Oral ingestion or IV infusion of too much salt
• Studies show "mistakes" were healthcare providers administered hypertonic 5% NACL instead of hypotonic 5% Dextrose, which lead to death due to hypernatremia.
• Ingestion of sea water ($300-500 \, \text{mEq/L}$)

Hypernatremia - Causes: Diabetes Insipidus

• Decrease In ADH secretion.
• CENTRAL DI – lack of ADH. Causes: head injury or surgery, 50% idiopathic.
• NEPHROGENIC DI – failure of the kidney to respond to ADH. Causes: electrolyte imbalances, drugs.

Hypernatremia - Causes: Diabetes Insipidus Signs

• Polyuria + Polydipsia (excessive urine + excessive drinking)
• Urine volume can range from 3 – 20 L in 24 hours.
• In complete DI: urinary SG + osmolality are low
• In partial DI: somewhat higher - the patient still has remaining ability to concentrate urine.

Hypernatremia - Causes: Diabetes Insipidus and Thirst

• The patient with an intact thirst mechanism will drink enough fluid to maintain sodium balance.
• If the patient is unable to perceive/respond to thirst or if IV fluids are inadequate, polyuria will lead to severe dehydration (hypernatremia and hyperosmolality of plasma) along with weight loss, tachycardia and even shock.

Hypernatremia – Clinical Signs: Laboratory Data

• Serum sodium > $145 \, \text{mEq/L}$
• Serum osmolality > $295 \, \text{mOsm/kg}$

Hypernatremia – Clinical Signs

1. Thirst
2. Elevated body temperature
3. Dry and sticky mucus membranes – specific sign for hypernatremia
4. Restlessness + weakness
5. Disorientation, delusions, hallucinations
6. Lethargic when undisturbed, irritable when stimulated
7. Stupor \ coma
8. Muscle irritability and convulsion
9. Sign of irritability and high pitched cry in infants.

Hypernatremia Mnemonic

• FRIED SALT
  • F: Flushed skin
  • R: Restless, Irritable, Anxious, Confused
  • I: Increased BP & fluid retention
  • E: Edema; Peripheral & Pitting
  • D: Decrease urine output & dry mouth
  • Skin flushes
  • S: Agitation
  • A: ver |
  • L: Low grade fever
  • T: Thirst

Hypernatremia – Clinical Signs: Dependence on Severity and Rate

• Signs and symptoms of hypernatremia are dependent on the degree and rate of increase In the serum sodium concentration.
• Severe neurological damage tends to occur with acute elevations in sodium greater then $158 \, \text{mEq/L}$
• Patients with chronic hypernatremia may be only mildly symptomatic with serum sodium concentrations .

Hypernatremia – Clinical Signs: Early vs. Progressed Signs

• Early signs: Thirst is the early sign, acting as a protection from hypernatremia.
• Hypernatremia will occur in those who's thirst mechanism is impaired, or ones who don’t have access to water.
• (elderly, disabled, infants, mental status)
• Lethargy, weakness, irritability: the early neurological signs.
• Progressed signs, in severe hypernatremia: Twitching, seizures, coma, death.

Hypernatremia – Clinical Signs: Convulsions and Brain Damage

• Convulsions may occur with an acute rapid increase in plasma sodium.
• Due to cellular dehydration (resulting from pulling of fluid from the cells into the hyperosmotic ECF)
• In severe hypernatremia – permanent brain damage can occur
  • Brain contraction
  • Tearing of vessels

Hypernatremia – Clinical Signs: Adaptation and FVD

• Hypernatremia that developed within days to weeks (slow) is associated with minimal to mild neurological symptoms because the CNS cells have time to adapt to hyperosmolar changes.
• Hypernatremia + FVD = will have signs of FVD as well (postural hypotension, tachycardia…)

Hypernatremia - Risks

• Increased risk for thrombosis
  • Hemoconcentration = blood is thicker
  • Reduced blood flow
  • Endothelial damage in vessels

Hypernatremia - Treatment

• Depending on the cause:
  • Addition of water \ removal of sodium

Hypernatremia – Treatment: Brain Protection

• There's too much sodium in the blood. This pulls water out of brain cells, making them shrink. Shrinking brain cells can cause confusion, bleeding, or coma.
• After a few hours, the brain makes its own particles to hold onto water. This helps stop the shrinking — it's the brain’s way to adapt.
• Rapid correction of hypernatremia is dangerous!
• If fluids are given too fast, the blood becomes too diluted. Now water rushes into the brain cells. This causes brain swelling (cerebral edema). The patient can get seizures, brain damage, or even die.

Hypernatremia – Treatment: Rate of Correction

• The maximal recommended rate of correction of the serum sodium is $0.5 \, \text{mEq/L/hour}$
  (or $12 \, \text{mEq/L}$
  in 24 hours) in symptomatic patients.

Hypernatremia – Treatment: Adding Water

• PO \ NG tube – the safest route.
• IV fluids – hypotonic saline \ D5% dextrose
• For hypernatremia + FVD (hypovolemia) – Isotonic saline 0.9% (to expand the plasma volume while still lowering the plasma sodium concentration.

Hypernatremia – Treatment: Diabetes Insipidus

• For central DI – administer ADH (po \ iv \ nasal spray)
• Careful fluid infusion
  • ADH complication: water retention, resulting in hyponatremia.
• For polyuria – thiazides (diuretics)
  • Act by decreasing the number of sodium ions that reach the distal tubules of the kidneys.

ADH Disturbances