SODIUM METABOLISM

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SODIUM METABOLISM

1. Extracellular fluid contains about 3000 mEq of sodium, which is the main osmotic component. An increase or decrease as small as 1% of the total extracellular fluid volume can have serious effects. About 30,000 mEq of sodium undergo filtration at the glomeruli each day.
2. Several factors are active in the regulation of sodium in the body.
a. Renin is the enzyme responsible for the conversion of antiotensinogen to angiotensin I. An angiotensin converting enzyme converts angiotensin I to angiotensin II. Angiotensin causes vasoconstriction as well as the secretion of aldosterone from the adrenal gland. Renal hypoperfusion, adrenaline and other catecholamines stimulate renin secretion from the juxtaglomerular apparatus of the glomeruli.
b. Aldosterone is a hormone that is controlled by the renin-angiotensin system and acts to increase reabsorption of sodium in the cortical collecting duct.
c. Dopamine from the kidney inhibits reabsorption in the proximal tubules.
d. Prostaglandins block reabsorption in the tubules and stimulate renal vasodilatation.
e. Atrial natriuretic peptide blocks reabsorption of sodium in the collecting duct.

HYPONATREMIA
Definition:
1 Hyponatremia is sodium level under 135 mEq/ml but is actually an excess of water
with no effect from the amount of total body sodium.
2 Hypotonicity is always associated with hyponatremia, whereas hyponatremia can be hyper-, iso- or hypotonic.
3 Hypertonic hyponatremia is caused by osmotically active particles in the extracellular fluid (such as glucose) and a shift of water from intracellular to extracellular fluid as a result. Thus, low serum sodium is accompanied by normal or high osmolality.
4 Isotonic hyponatremia is also called pseudohyponatremia since it is an artifact caused by high lipid or protein in the serum.
5 True hyponatremia is hypotonic with sodium is under 125 mEq/ml and serum osmolality under 250 Osm/kg.
6 Hyponatremia can further be divided into hypovolemic states (GI, renal or third-space losses), isovolemic states and hypervolemic states (CHF, nephrotic syndrome, cirrhosis).
Etiology:
1 Increased fluid intake – more than 1000 ml/hour is more than the body is able to excrete and so water concentration exceeds sodium concentration. This is seen in psychiatric patients with water intoxication or in patients given hypotonic fluids intravenously in large amounts. This is isovolemic hyponatremia.
2 Decreased excretion of water
a. Increased reabsorption in the proximal tubules may reduce the kidney’s ability to excrete water. This can be caused by hypoperfusion due to hypovolemia, or disease states such as congestive heart failure, cirrhosis, or nephrotic syndrome (hypervolemia). The urine is low in sodium, due to increased reabsorption also of sodium. BUN is high.
b. A GFR that falls to less than 10% of normal reflects a decrease in the kidney’s ability to deal with water excretion.
c. Increased reabsorption in the collecting tubules is caused by ADH secretion that is not osmotically stimulated. Urine sodium is normal, with high urine osmolality.
3 SIADH (syndrome of inappropriate ADH secretion) is non-osmotically induced and connected with various disorders of the CNS (tumors, trauma, psychiatric disturbances) and of the lungs (oat cell carcinoma, infection, bronchospastic disease). It is also seen with hypopituarism due to primary adrenal insufficiency or impaired ACTH secretion, and with various drugs, particularly chlorpropamide, clofibrate, carbamazepine, and thiazide diuretics. Idiopathic SIADH may occur in the elderly and is probably connected to increasing ADH secretion with age. One type of SIADH, called “reset osmostat” is seen in patients with chronic illness or malnutrition. The set point for sodium concentration is lowered and the body maintains that value. SIADH is isovolemic.
Manifestations:
1 Depend on the underlying problem.
2 Hyponatremia may cause edema of brain tissues. Acute hyponatremia may cause acute CNS dysfunction with obtundation, coma, seizures and even death. Prolonged hyponatremia may cause permanent CNS damage due to edema of brain cells.

Diagnosis:
1. Plasma is hypotonic and urine osmolality is more than 50-100 Osm/kg.
2. Urine sodium is high in SIADH, but low with edema or hypovolemic states.
3. Water loading test – the patient is given 20ml/kg of water over 20-40 minutes. 80% of this should be excreted within 4 hours with urine osmolality below 100 Osm/kg afterward. If not, the kidney’s ability to excrete water is impaired.

Principles of management:
1 The first step is to reduce fluid intake to about 700 ml/day.
2 The giving of hypertonic infusions such as 3% sodium chloride will increase tonicity of the extracellular fluid. Serum sodium concentration should be increased slowly, no more than 2 mEq/hr. Too rapid correction may cause central pontine myelinolysis. Since rapid volume expansion may cause pulmonary edema, usually a diuretic such as furosemide is given at the same time. The goal is to reach a serum sodium level of 125 mEq/ml. Further correction to normal values can be done more slowly. The formula used is:

(125 – current Na level) x total body water (which equals body weight x 0.6) = mEq of hypertonic saline needed

3 Furosemide given with saline will increase water excretion transiently.
4 Demeclocycline acts on ADH-controlled movement of water in the collecting tubule. Dose is 600-1200 mg/day and several days are required to show an effect. This drug should not be used in patients with kidney disease, heart failure or liver disease.

Prognosis:
1. Acute hyponatremia can cause increased intracranial pressure and brain
damage.
2. Chronic hyponatremia may have a permanent effect on cognitive functions – the theory is controversial.



HYPERNATREMIA

Definition:
1. Hypernatremia is clinically significant above 155 mEq/ml.
2. Hypernatremia is always hypertonic.

Etiology
1. Renal causes
a. Decreased effect of ADH
(1) central diabetes insipidus – failure of secretion or synthesis of ADH due to tumor, trauma, sarcoidosis or histiocytosis
(2) nephrogenic diabetes insipidus – high levels of ADH with no effect, due to renal disease, sickle cell anemia, urinary tract obstruction, hypercalcemia, hypokalemia, lithium or demeclocycline use.
b. Osmotic diuresis as in hyperglycemia – both water and sodium reabsorption are affected, but water losses are more than sodium losses.

2. Extrarenal causes
a. Reduced fluid intake – the body loses water through urine and feces, as well as insensible losses via the skin and mucus membranes. A minimum of about 700 ml/day is necessary in cool climates, more in warmer areas.
b. Vomiting and diarrhea increase gastrointestinal losses.
c. Sweating and burns increase losses via the skin.

Manifestations:
1 Most of the volume decrease is in intracellular fluid, but there is also a slight decrease in extracellular fluid.
2 Urine volume is reduced in cases of extrarenal water losses and normal kidney function. Polyuria is seen with renal causes.
3 Young children and the elderly may show CNS depression with obtundation, coma or seizures. Intracranial or subarachnoid hemorrhages may result from the tearing of bridging veins as brain volume decreases.

Diagnosis
1. Water deprivation test – the patient is given no fluids from 20:00 for 14 hours at which point urine osmolality is tested. It should be greater than 800 Osm/kg. An injection of 5 units ADH is then given which normally does not further increase osmolality. ADH deficiency is suspected if osmolality does not reach 800 after 14 hours or increases by more than 15% after ADH is injected. With nephrogenic diabetes insipidus, the osmolality will be less than 300 with no increase after ADH injection.
2. Urine osmolality under 150 Osm/L is characteristic of a primary problem of water conservation. Urine osmolality over 150 Osm/L with polyuria is characteristic of osmotic diuresis.
3. Urinary concentrations of sodium, glucose and urea may help to determine etiology. Bicarbonate diuresis manifests with a urine pH exceeding 6.
4. Actual ADH levels may need to be assayed in plasma since urine osmolality does not reflect ADH levels in nephrogenic diabetes insipidus.

Principles of management:
1 Fluids, either intravenous as 5% dextrose or orally as water, should be given. Hemolysis may result if fluids given are hypotonic less than 150 Osm/L.
2 Thiazide diuretics reduce polyuria by stimulating reabsorption of sodium and water in the proximal tubule. They are effective in nephrogenic diabetes insipidus.
3 ADH or vasopressin may be given as a nasal spray, 10-20 mg every 12 hours.
4 Drugs that cause SIADH may be useful.

Complications: only if access to water is limited


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