Sodium Regulation
Physiological basis
K+:< ICF: 150 meq/L
ECF: 3.5 -5 meq/L
- Sodium is the major ECF cation (sodium value 140 mEq/L ECF vs 25 mEg/L intracellular).
Total body k+- 3500meq
- Total body sodium is about 5,000 mEq in a normal adult person.
- 85-90% sodium is extracellular.
K+ -98% Intracellular
2%. Extracellular
- Sodium is responsible for more than 90% of total osmolality of extracellular fluid.
- Major function of sodium is to maintain ECF volume and therefore maintain blood pressure.
- ECF volume is reflection of total body sodium content (amount).
- Daily requirement of sodium is about 100 mEq or 6 gm of sodium chloride.
K+ requirement is 50-80 meq day
- Excess salt is excreted chiefly by kidney. Loss of sodium in sweat is poor (30-65 mEq/L).]
Response to sodium deficit
- Deficiency of sodium in body will lead to hypovolemia and activates Angiotensin-Il and Aldosterone.
- By acting on the kidney, angiotensin-Il helps to increase sodium absorption at the proximal tubules and aldosterone at the collecting duct.
- In a state of sodium deficit, absorption of Na under aldosterone control is so perfect that almost no urinary Na loss occurs. So by almost complete absorption of Na kidney helps to prevent sodium loss.
Renal priority
- To reclaim sodium under aldosterone influence, initially potassium and it needed later on Htis lost in the urine.
- Due to body’s priority to reclaim Na > H > K, during abnormal loss of all electrolytes (like in diarrhoea) hypokalemia is the commonest abnormality.
Response to sodium excess
- When there is excess amount (content) of sodium it will lead to increased ECF volume, which will lead to decreased Angiotensin-ll, Aldosterone and increase in ANP.
- Decreased angiotensin-ll and aldosterone level will lead to decreased renal reabsorption of sodium.
- Increased ANP will lead to natriuresis and diuresis.
- Hence net result is increased urinary excretion of sodium. Thus extra sodium will be lost.
HYPERNATREMIA
Hypernatremia is defined as plasma sodium concentration greater than 145 mEg/L. Hypernatremia is a less frequent disorder and indicates either lack of water or primary sodium gain.
HYPERNATREMIA IS USUALLY DUE TO WATER DEFICIT AND NOT SODIUM OVERLOAD.
The thirst mechanism is very effective in preventing hypernatremia. So hypernatremia usually does not occur unless there is non-availability of water, impaired thirst or comatose-confused patient unable to drink water.Therefore, hypernatremia is seen chiefly in very young, very old and very sick or debilitated patients. Pure water deficit leading to hypernatremia is called dehydration.
ETIOLOGY
Common causes of hypernatremia are summarized in Table No. 3.4.
Etiology of hypernatremia
Excess water loss.
A.Insensible loss
Dermal : Heat exposure, severe burns, severe exercise.
Respiratory : Patient on mechanical ventilator.
B.Renal loss :
Diabetes Insipidus (central or nephrogenic)
Excessive diuretics, uncontrolled DM
C.Gastrointestinal losses
Osmotic diarrhoea.
Water deficit due to impaired thirst.
- Primary hypodypsia, confused or comatose conditions.
Sodium retention.
- Excessive I.V. hypertonic NaCI or NaHCO3
CLINICAL FEATURES
Clinical features of hypernatremia are primarily neurological and they depend upon the rapidity of onset, its duration and its magnitude.This is the only state in which dry sticky mucous membrane is characteristic and body temperature is generally elevated. Major neurological symptoms include nausea, muscular weakness, altered mental status, neuromuscular irritability, focal neurological deficit and occasionally coma or seizures.
In severe acute hypernatremia brain shrinkage may be substantial,exerting traction on the venous sinuses. It can cause intracerebral and subarachnoid hemorrhage which may produce irreversible neurological deficit or even death. The patient may also complain of polyuria or excessive thirst. The signs and symptoms of volume depletion are often present in patient with history of excessive sweating, diarrhea or osmotic diuresis.
Even though there is equal volume of fluid losses, why the patients with hypertonic dehydration are haemodynamically more stable than the patients with isotonic volume depletion
Pure water loss leads to dehydration with hypernatremia (hypertonic dehydration), whereas proportionate combined loss of water and salt in isotonic volume depletion leads to hypovolemia and has normal serum sodium.
In isotonic volume depletion, fluid loss leads to reduction only in ECF volume (and therefore early reduction in intravascular volume) leading to hypotension and reduction in tissue perfusion. While in dehydration due to pure water depletion there is proportionate reduction in total body water (2/3 from ICF and 1/3 from ECF). As ECF volume depletion land therefore intravascular volume depletion, which is 1/4 of ECF) is much less, clinical features are lesser in pure water depletion
DIAGNOSIS
Complete history and examination may provide the clue for etiology of hypernatremia. Renal and glycaemic status, urinary volume, osmolality and glycosuria and response to vasopressin in diabetes insipidus are useful for etiological diagnosis of hypernatremia
TREATMENT
The therapeutic goals are :
1.To stop ongoing fluid loss by treating the underlying causes.
2.To correct water deficit.
Two important factors to decide treatment plan are
i.ECF volume status and
il.Rate of development of hypernatremia.
The important treatment aspects are
- To diagnose and treat specitic etiology (i.e. treating diabetes insipidus,DM, hypokalemia, hypercalcemia etc. and stopping diarrhoea)
- Fluid deficit : The amount of water required to correct the deficit can be calculated from the following equation.
Water deficit = Plasma Na-140 × 0.6 x body weight in kg.
140
- In addition to water deficit, ongoing and insensible loss needs to be replaced. Correct the total fluid deficit over 48-72 hours.
- Rate of correction : In acute hypernatremia the water deficit can be replaced relatively rapidly, without increasing the risk of cerebral edema. In acute hypernatremia targeted rate of correction of hypernatremia is 1 mEq/L/hr. Rapid correction of chronic hypernatremia is dangerous. It may lead to neurological problems due to development of cerebral edema. Safe rate of correction is reduction of serum sodium by 1 mEq/every 2 hours or 10 mEq/L over first 24 hours.
- Goal of treatment : The goal is to reduce serum Na concentration to 145 mEg/L.
- Deterioration of neurological symptoms after initial improvement suggests the development of cerebral edema and requires temporary discontinuation of water replacement
- Treatment of hypernatremia is water. The safest route of administration of water is by mouth or via a nasogastric tube.
- Acute hypernatremia is treated vigorously with D-5% infusion.Large and rapid infusion of D-5% will lead to hyperglycemia and osmotic diuresis, which may aggravate hypernatremia. If required,hyperglycemia can be combated with insulin therapy.
- Hypernatremia with ECF volume contraction: If there is severe loss of ECF volume with hypotension and azotemia, isotonic saline is given initially until the ECF volume is restored. Subsequently water deficit can be replaced with water by mouth or I.V. 5%-dextrose or 0.45% NaCI.
- Sodium concentration of 0.9% NaCI (154 mEq/L) is greater than the normal serum sodium (140 mEq/L), but is generally lower than the serum sodium concentration in hypernatremia. So initial therapy with 0.9% Nacl,has an advantage of rapid correction of hypotension and avoiding unnecessary rapid fall of serum sodium.
- Method to calculate change in serum Na for given infusate : Change in serum Na concentration, for the infusion of one litre of appropriately selected I. V. fluid, can be calculated by formula mentioned below
Change in serum sodium concentration =
Infusate Na/L – Serum Na
Total body water (L) + 1
or
Infusate (Na + K)/L – Serum Na
Total body water (L) + 1
(For details of Na concentration of infusate and method to calculate total body water refer treatment of hyponatremia).
- Hypernatremia with increased ECF volume : In these patients hypernatremia is secondary to solute administration. The hypernatremia is acute and can be rapidly corrected. These patients are usually volume overloaded. A loop diuretic is administered along with water to facilitate sodium excretion. In patient with massive overload or renal failure dialysis may be necessary.
HYPONATREMIA
Hyponatremia is defined as plasma sodium less than 135 mEg/LHyponatremia is not uncommon in a hospitalized patient (incidence 1.5 to 2.5%), but is rarely seen in an ambulatory patient (if present, reflects a chronic disease status).
Serum sodium reflects the relative proportion of sodium and water.
Hyponatremia usually means water overload and not sodium deficit.
Hyponatremia can occur with normal, low or even high total body sodium.
So basically hyponatremia can be dilutional ( water excretion lesser than water intake and so needs fluid restriction as the most important treatment) or due to sodium loss (needs sodium and fluid supplementation).
- Hyponatremia usually means water retention
ETIOLOGY
Low serum Na leads to decreased serum osmolality, so true hyponatremia is characterized by hypoosmolality. ECF volume varies in hyponatremic patients, depending upon etiology. So etiology of hyponatremia is classified on basis of these two criteria, osmolality and ECF volume.
Pseudo hyponatremia (increase Lipids, increase Proteins, +increase Carbs)
- Normal osmolality: Hyperlipidaemia, Hyperproteinaemia
- High osmolality:Hyperglycaemia, Mannitol
Hyposmolar hyponatremia (true hyponatremia)
A.Hyponatremia with ECF volume depletion
Patient dehydrated reduction in total body sodium exceeds reduction in total body water)
1.Extra renal loss (Urinary sodium < 15 mEq/L)
Vomiting, diarrhea, peritonitis.
2.Renal loss (Urinary sodium > 20 mEq/L)
Excessive diuretics, salt losing nephropathy, diabetic
ketoacidosis, cerebral salt wasting syndrome.
B. Hyponatremia with hypervolemia, increased CF volume
Patient oedematous- Increase in total body water exceeds
increase in total body sodium)
Urinary sodium < 20 mEq/L : CHF, cirrhosis and nephrotic syndrome.
Urinary sodium > 20 mEq/L : Renal failure
C.Hyponatremia with normal ECF volume
(Patient normovolemic, increased total body water)
- SIADH, post operative pain, hypothyroidism, glucocorticoid deficiency, psychogenic polydypsia, drug induced.
CLINICAL FEATURES
The severity of symptoms depends upon the severity of hyponatremia and the rate at which the plasma sodium concentration is lowered. So acute and severe hyponatremia is symptomatic but chronic and mild hyponatremia is well tolerated. The very young and elderly patients are more symptomatic.
| Mild | Moderate | Severe |
| Anorexia | Personality changes | Drowsiness |
| Headache | Muscle cramps | Diminished reflexes |
| Nausea | Muscular weakness | Convullsions |
| Vomiting | Confusion | Coma |
| lethargy | ataxia | Death |
DIAGNOSIS
History and physical examination is often helpful in identifying hypovolemic hyponatremia (diarrhea, vomiting, burns, diuretics etc.)
Three important diagnostic tests are
1. Plasma Osmolality
Low : True hyponatremia
Normal or elevated : Pseudohyponatremia or renal failure.
2. Urine Osmolality
< 100 mOsm/kg or specific gravity < 1.003, diluted urine suggest primary polydypsia with normal water excretion.
> 100 mOm/kg, other causes of hyponatremia in which water excretion is impaired.
3. Urine Sodium Concentration :
< 15 mEq/L effective volume depletion e.g. diarrhea, vomiting
> 20 mEq/L SIADH (normo volemia) or renal salt wasting (diuretics, renal disease or hypoaldosteronism)
Hyponatremia is usually associated with low plasma osmolality. But if osmolality is normal or high, rule out pseudohyponatremia
Normal plasma osmolality i2 275- 290 mOsm/kg.
Plasma= 2× Na +Glucose (mg/dI) + BUN (mg/dI)
Osmolality 18 2.8
- Associated hyperkalemia suggests renal insufficiency or adrenal insufficiency with hypoaldosteronism.
- Associated hypokalemia and metabolic alkalosis suggest vomitina or diuretic therapy.
- Diuretics induced hyponatremia is almost always due to thiazide diuretics. (Loop diuretics:Water diuresis > hyponatremia infrequent).
TREATMENT
Treatment of hyponatremia must be individualized considering etiology, rate of development (acute vs. chronic), severity and clinical signs and symptoms.dictum; hyponatremeia which davelops quickly, should be treated fast.Whereas hyponatremia, which develops slowly, should be corrected slowly.
Goal of therapy
1.To raise the plasma sodium concentration at a safe rate.
2.To replace sodium deficit or potassium deficit or both.
3.To correct underlying etiology.
In general hyponatremia is corrected acutely by giving sodium to patients who are volume depleted and by restricting water intake in patients who are normovolemic or oedematous.
Specific treatment
- Removal of the drugs responsible for hyponatremia:
- Thiazide Diuretics, Chlorpropamide or .V. Cyclophosphamide.
- Management of physical stress, (postoperative pain).
- Specific treatment for adrenal insufficiency, hypothyroidism, nephrotic syndrome, CHF, uncontrolled diabetes or ketoacidosis,salt losing nephropathy etc.
1. Hyponatremia with hypovolemia
These patients require fluid and salt supplementation which can be done with I.V, isotonic (0.9%) NaCI (or even oral salt containing water) at rate appropriate for the estimated volume depletion. Intake of simple water or I.V. fluid with low Na (0.45% NaCI, Isolyte-M, 5%-dextrose, etc.) should be restricted until the plasma sodium is within the normal range, because it will aggravate hyponatremia.
Diuretics induced hyponatremia is treated with saline with postassium supplementation (30-40 mEq/L).
2 Hyponatremia with hypervolemia (Oedematous state)
Therapy is difficult in oedematous state since sodium supplementation will worsen fluid overload. Such patients are treated with diuretics, salt restriction, fluid restriction (intake < urine output) and correction of potassium deficit in addition to the etiological treatment.
3.Hyponatremia with euvolemia
Hyponatremia with normal or high ECF volume has impaired water excretion with normal or high total body sodium. In such patients fluid restriction is the most important treatment. Adequate restriction of fluid intake will gradually increase serum sodium concentration.
Basic principles of correction of hyponatremia
Treatment of hyponatremia should balance the risk of hypotonicity due to hyponatremia and the risk of therapy.
- To treat or not to treat :
How rapidly hyponatremia should be corrected is a dilemma, Patients with severe hyponatremia (110-115 mEq/L) are at risk of developing severe and potentially irreversible neurological damage and sometimes even death. On the other hand, too rapid correction of severe hyponatremia can produce central pontine myelinosis or osmotic demyelination syndrome (ODS), which can cause substantial morbidity and mortality.
- When to treat,When not to treat :
A.Patient with seizures or other severe neurological symptoms due to hyponatremia needs prompt treatment. In this setting, risk of untreated hyponatremia and cerebral edema is greater than the potential harm of rapid correction. So rapid correction is indicated in acute (<48 hours) symptomatic or severe (serum Na < 120 mEq/L) hyponatremia.Ön the other hand, chronic (> 48 hrs) and mild hyponatremia, with minimal neurological symptoms are at little risk due to hyponatremia. However, these patients can develop demyelination following rapid correction. So there is no necessity to correct these patients rapidly and they should be treated using slower acting therapy such as fluid restriction. Pay particular attention to premenopausal women, elderly and young children as they are more symptomatic and need early treatment.
Chronic asymptomatic hyponatremia
- The targeted rate of plasma sodium should not be greater than 0.5 to 1.0 mEq/L/hour.
- Raise the plasma sodium by less than 10 to 12 mEq/L on the first day and less than 18 mEq/L over the first two days. As per recent recommendations a targeted rate of correction should not exceed 8 mEq/L on any day of treatment.
- If the rate of correction is faster or rise in serum sodium is > 25 mEq/48 hours or correction is made until normonatremia (serum sodium 140 mEq/L) is achieved there is high risk of central pontine myelinosis.
Acute hyponatremia with severe neurological symptoms
These patients require rapid correction of plasma Na with hypertonic saline. Initial rate of rise of Na concentration should be 1.5-2 mEq/L/hr for the first 3 to 4 hours or until the severe neurological symptoms improve. Besides this initial rapid correction rise in the plasma sodium concentration should not exceed 10-12 mEg in first 24 hours. Patient with seizures also require immediate anticonvulsant drug therapy and adequate ventilation.
How long to treat and when to stop acute correction of hyponatremia
A.Regardless of the initial rate of correction, chosen acute treatment should be interrupted once any of the three end points is reached
1) Patient’s symptoms are abolished.
2) A safe plasma sodium (generally 120-125 mEq/L) is achieved or
3.A total magnitude of correction of 20 mEq/L is achieved. It is necessary to correct hyponatremia accurately to a safer range,rather than correcting completely to normonatremia.
Fluid should be used to correct hyponatremia
- Aim of fluid infusion is to raise Na. by correcting Na delicit, so the infused fluid should contain higher Na concentration than desired or normal serum sodium concentration.
- 0 9% saline (154 mEQ/L Na) and 3% NaCl-hypertonic saline (513mEq/L Na) are the only two routinely used IV fluids which have higher Na concentration and therefore are used to correct hyponatremia. However, for the treatment of hyponatremia due to SIADH, infusion of 0.9% NaCI is inappropriate.
- When hyponatremia is associated with hypovolemia or in absence of fluid retention or edema, 0.9% saline is the preferred fluid.
- But when patient needs salt supplementation along with fluid restriction hypertonic saline is the preferred fluid (e.g. severe form of SIADH).
Monitor Na during treatment of hyponatremia
During treatment of hyponatremia, many other independent factors can modify the Na concentration (e.g. urinary and other losses of Na, addition of oral fluid intake etc.). So frequent monitoring of the serum sodium concentration (atleast at 4 to 6 hours interval initially), is necessary to ensure that the rate of correction is as desired and in order to make further adjustment in the amount and rate of fluid administration. Remember, in symptomatic/sick patients with hyponatremia, calculation of the requirement of Na containing IV. fluids for whole 24 hours and their infusion without proper monitoring and modification can be dangerous.