4.1 Water distribution between body compartments
The diagram below illustrates water distribution between intracellular and extracellular body compartments, the latter including interstitial and intravascular spaces.
4.2 Sites of electrolyte reabsorption
The simplified diagram below illustrates important sites of electrolyte reabsorption in the nephron and where Na + reabsorption can be inhibited by diuretics.
4.3 Hypernatremia ,
Causes of hypernatremia are divided into three categories based on the patient’s volume status, as shown in the diagram below. Hypernatremia occurs in only 0.1% to 0.2% of hospitalized patients. It is always associated with hypertonicity (hyperosmolality).
4.3.1 Hypernatremia: Causes
4.3.2 Hypernatremia clinical manifestations
The clinical manifestations of hypernatremia depend upon rapidity of onset, duration, and magnitude of hypernatremia.
Alteration of brain water content with brain volume loss:
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In severe cases (generally with serum Na + >160 mmol/L): substantial brain shrinkage, traction of the venous sinuses and intracerebral veins leading to rupture and hemorrhage
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In less severe cases: nonspecific symptoms (nausea, muscle weakness, fasciculations, decreased mental status)
Complications of aggressive treatment:
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Adaptation to hypernatremia results in the uptake of idiogenic osmoles by brain cells, resulting in brain edema when overly rapid rehydration takes place (causing seizures, decreased mental status).
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However, the complications as a result of overly rapid correction of chronic hypernatremia (in <48 hr) are described predominantly in pediatric patients. ,
4.3.3 Treatment of hypernatremia
For practical purposes one can imagine that the body maintains the homeostasis of the basic components in the following order of priority:
- 1.
Circulatory volume
- 2.
Osmotic equilibrium
- 3.
Electrolyte concentration
Similarly, in the treatment of electrolyte disorders, therapeutic measures should be directed at the same aspects in the same order (e.g., attempts to correct the circulatory volume should take priority and precede correction of sodium concentration and osmolality).
Helpful points in treating hypernatremia:
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In patients with hypovolemia, start with volume expansion with normal (isotonic) saline or lactated Ringers solution, then correct water deficit either with oral water replacement or with intravenous (IV) half-normal saline or dextrose 5% in water.
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In patients with hypervolemia, treat with water + loop diuretic to avoid pulmonary or cerebral edema. Recall that only about 10% of “free” water, typically provided with 5% dextrose intravenously, is maintained intravascularly, and thus contribution to additional volume overload is modest.
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Replace calculated water deficit (see formula below) plus ongoing losses (urinary, gastrointestinal [GI]) plus insensible losses (no more than half of the calculated water deficit in the first 24 hr to prevent cerebral edema).
- ■
Reduce Na + concentration by ≤ 1 mmol/L/hr (≤1 mEq/L/hr) if symptomatic initially, but do not reduce Na + by more than 12 mmol/L/day.
- ■
When symptoms are resolved, replace the remaining water deficit within 24 to 48 hours.
- ■
In acute hypernatremia (<48 hr duration), the water deficit should be corrected rapidly to prevent cerebral hemorrhage or acute osmotic demyelination.
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Worsening neurological status after initial improvement suggests brain edema. Discontinue water replacement.
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Central diabetes insipidus (CDI)—treat with desmopressin (DDAVP)
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Nephrogenic diabetes insipidus (NDI): Thiazides inhibit urinary diluting capacity and cause mild intravascular volume depletion, which decreases water delivery to the collecting duct, which in turn decreases polyuria for symptomatic benefit.
- ■
Amiloride for lithium-induced NDI: Like thiazides, amiloride decreases polyuria, but spares excessive K + wasting and may diminish lithium toxicity (by blocking lithium entry into collecting duct cells in exchange for Na + ).
Water deficit to correct in hypernatremia:
Water deficit to correct in hypernatremia (assuming distribution volume of Na + to be 0.6 of the body mass):
Waterdeficit(L)=SerumNa+(mmol/L)−140140×0.6×Bodymass(kg)
4.4 Hyponatremia ,
Hyponatremia is relatively common, occurring in 1% to 2% of hospitalized patients. Unlike hypernatremia (which is always associated with hypertonicity), hyponatremia can be associated with hypotonicity, isotonicity, or hypertonicity. To identify the cause of hyponatremia one has to collect the following information: plasma osmolality, patient volume status, urine sodium concentration, and urine osmolality (Uosm), the latter which reflects antidiuretic hormone (ADH) secretion. , ,
Plasma osmolality
Volume status and urine NA +
Helpful points for syndrome of inappropriate antidiuretic hormone secretion (SIADH):
- ■
Α low ADH level results in diluted urine, so Uosm <100 mOsm/Kg (e.g., in primary polydipsia/“beer potomania”).
- ■
SIADH is the most common cause of euvolemic hyponatremia. SIADH is hard to distinguish from cerebral salt wasting as volume status might be difficult to estimate, but cerebral salt wasting is usually due to intracranial hemorrhage and much less common. It does not have strict diagnostic criteria or lab tests associated with it, though management is often similar to SIADH. Both can be treated with 3% (hypertonic) saline, making differentiation in an urgent clinical scenario of little importance. ,
- ■
Diagnostic criteria for SIADH: hypoosmolarity (serum osmolarity <280 mOsm/kg); hyponatremia (Na + ≤134 mEq/L) with clinical euvolemia; urinary Na + >40 mEq/L; inappropriately concentrated urine (Uosm >100 mOsm/kg); and normal adrenal, thyroid, cardiac, renal, and hepatic function, frequently with hypouricemia. ,
Differential diagnosis of SIADH
SIADH is the most frequent cause of hyponatremia in a hospitalized patient. It is important to identify the underlying cause of SIADH, as it may be due to serious or even urgent medical conditions, or may recur.
Malignant neoplasia:
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Carcinoma (bronchogenic, duodenal, pancreatic, ureteral, prostatic, bladder)
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Lymphoma and leukemia
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Thymoma, mesothelioma, and Ewing’s sarcoma
Central nervous system (CNS) disorders:
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Trauma, subarachnoid hemorrhage, and subdural hematoma
- ■
Infection (encephalitis, meningitis, brain abscess)
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Tumors
- ■
Porphyria
- ■
Stroke
- ■
Vasculitis
Pulmonary disorders:
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Tuberculosis
- ■
Pneumonia
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Vasculitis
- ■
Mechanical ventilators with positive pressure
- ■
Lung abscess
Drugs:
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Desmopressin
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Vasopressin
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Chlorpropamide
- ■
Thiazide diuretics
- ■
Oxytocin
- ■
Haloperidol
- ■
Phenothiazines
- ■
Tricyclic antidepressants
- ■
High-dose cyclophosphamide
- ■
Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs)
- ■
Vinblastine/vincristine
- ■
Nicotine
Other:
- ■
“Idiopathic” SIADH
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Hypothyroidism
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HIV infection
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Guillain-Barre syndrome
- ■
Multiple sclerosis
- ■
Nephrogenic SIADH (hereditary V2 receptor mutation )
4.4.1 Clinical manifestations of hyponatremia
Symptoms of hyponatremia depend on:
- ■
the degree and rapidity of onset,
- ■
underlying CNS status, and
- ■
οther metabolic factors such as:
- ■
hypoxia,
- ■
acidosis,
- ■
hypercalcemia, and
- ■
hypercapnia.
- ■
The underlying mechanism of symptoms is hypoosmolar encephalopathy (brain edema from water shift):
- ■
Mild symptoms: headache, nausea
- ■
More severe symptoms (usually with Na + <125 mmol/L): confusion, obtundation, focal neurological deficits, seizures
4.4.2 Treatment of hyponatremia
As in the case of hypernatremia, the therapeutic measures aimed to correct hyponatremia should be directed at correcting the circulatory volume first and then at correcting the sodium concentration. If the hyponatremia developed rapidly (<24 hr), it should be corrected rapidly; if it developed slowly, it should be corrected slowly to decrease the risk of a CNS demyelinating syndrome.
Additional considerations for using 3% NaCl:
- ■
Stop infusion if symptoms are abolished, or if serum Na + has risen to ≥125 mEq/L.
- ■
Correct serum Na + at 0.5 mEq/L/hr (max 1 mOsm/kg/hr), initially raising Na + not more than 8 mEq/L over the first 24 hours and 18 mEq/L over the first 48 hours.
- ■
Rapid osmolality correction can cause demyelination syndrome, as well as pontine and extrapontine myelinolysis, with substantial neurological morbidity and mortality.
- ■
Overly rapid correction or overcorrection can occur with vasopressin antagonists as well. ,
Calculations to establish the rate of 3% NaCl infusion
Calculations are based on the following assumptions: although NaCl is distributed mainly in the extracellular space, the distribution volume of NaCl is total body water, or therefore, roughly 0.6 × body mass in kg. The calculations below are crude approximations since they do not account for the rate of Na + and water excretion or potassium losses.
As 1 liter of 3% NaCl has 512 mmol of Na + (0.512 mmol/mL), if the rate of correction of serum Na+ is to be 0.5 mmol/L/hr, the rate of infusion of 3% NaCl infusion in mL/hr will be = 0.5/0.512 × 0.6 body mass (in kg).
Calculation of total Na deficit to correct hyponatremia
CalculatedNa+Deficit(mmol)=0.6(Bodymass[kg])×(140−SerumNa+[mmol/L])
If volume depletion is present, replace estimated volume deficit in liters with normal saline in addition.
Relative risk versus benefit in treatment of hyponatremia:
| Risk of Uncorrected Hyponatremia | Risk of Demyelination | |
|---|---|---|
| Rapid onset, symptoms | Higher | Lower |
| Slow onset, asymptomatic | Lower | Higher |
4.5 Hypokalemia
Similar to other electrolytes, hypokalemia can be explained by either lower intake, higher excretion, or intracellular redistribution of potassium. To identify the cause of hypokalemia, the following tests are very helpful: urine potassium, and for concentrated urines (Uosm >300 mOsm/kg), the transtubular potassium gradient (TTKG; described below), urine chloride, and plasma bicarbonate.
Transtubular potassium gradient (TTKG)
The concept of TTKG helps to identify renal wasting of potassium (high TTKG), as opposed to GI losses or intracellular shift (low TTKG). TTKG compensates for a high urinary concentration, above 300 mOsm/kg, which raises the U K concentration by removing tubular fluid from the final urine, but without excreting more potassium.
Note that this formula is valid only when Uosm >300 mOsm/kg and U Na + >25 mEq/L, and should not be used to “correct” for dilute urines.
TTKG=UrineKPlasmaK÷UrineOsmPlasmaOsm=UKPK×POsmUOsmTTKG<3: GI loss, intercellular redistribution with renal K conservationTTKG<8: Inadequate renal K excretion when hyperkalemicTTKG>5: Renal K wasting when hypokalemicTTKG>8: Denotes appropriete renal and aldosterone effect when hyperkalemic
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