Fluid and Electrolyte Balance (Primary Regulatory Hormones (Antidiuretic…
Fluid and Electrolyte Balance
Total body water (TBW) is about 60% of body weight (ranging from about 50% in obese people to 70% in lean people).
2/3 of TBW is in the intracellular compartment (intracellular fluid, or ICF); the other 1/3 is extracellular (extracellular fluid, or ECF).
About 25% of the ECF is in the intravascular compartment; the other 75% is interstitial fluid.
About 1- 2 % of the ECF is in transcellular fluids – CSF, intraocular fluids, serous membranes, and in GI, respiratory and urinary tracts (third space)
Clinical Assessment of ECF Volume (Total Body Na+)*
Main Cations and Anions
ECF: Cations (sodium), Anions (chloride, bicarbonate).
ICF: Cations (potassium), Anions (phosphate ions, negatively charged proteins)
Sodium and potassium concentrations in extra- and intracellular fluids are nearly opposites
osmotic concentration of ICF and ECF Is identical even though the composition of the ICF and ECF are different
Osmosis eliminates minor differences in concentration because cell membranes are permeable to water
Two-way water flow is substantial
Compartmental exchange is regulated by osmotic and hydrostatic pressures
Principles of Fluid and Electrolyte Regulation
All of the body’s homeostatic mechanisms that monitor and adjust body fluid composition respond to changes in the ECF, not in the ICF
No receptors directly monitor fluid or electrolyte balance (only volume and osmolarity)
Cells cannot move water molecules by active transport
The body’s water or electrolyte content will rise if dietary gains exceed environmental losses, and will fall if losses exceed gains
Water intake and exertion
Water intake is regulated by thirst. Thirst is triggered by receptors in the hypothalamus that respond to increased plasma osmolality or decreased body fluid volume. Rarely hypothalamic dysfunction decreases the capacity for thirst.
Water excretion by the kidneys is regulated primarily by ADH (vasopressin). ADH is released by the posterior pituitary and results in increased water reabsorption in the distal nephron
Primary Regulatory Hormones
Antidiuretic Hormone (ADH)
Stimulates water conservation at kidneys:
reducing urinary water loss, concentrating urine
Stimulates thirst center:
promoting fluid intake
Osmoreceptors in hypothalamus monitor osmotic concentration of ECF (plasma, CSF)
Change in osmotic concentration in plasma and CSF alters osmoreceptor activity
Osmoreceptor neurons secrete ADH in proportion to osmotic concentraiton via the posterior pituitary
secreted by adrenal cortex in response to:
-rising K+ (sensed at the adrenal cortex) or falling Na+ levels in blood
-activation of renin–angiotensin system (due to changes in blood volume)
Determines rate of Na+ absorption and K+ loss along DCT and collecting system
“Water Follows Salt”
High plasma aldosterone concentration causes kidneys to conserve salt
Conservation of Na+ by aldosterone also stimulates water retention
ANP and BNP are released by cardiac muscle cells in response to abnormal stretching of heart walls due to elevated blood pressure or volume
Block release of ADH and aldosterone
Lower blood pressure and plasma volume
If water is lost, but electrolytes retained, ECF (and ICF) have higher concentrations, lower volumes
Hypothalamus senses elevated ECF osmolarity this and releases ADH to restore fluid balance
New water in the ECF will shift into ICF and restore volumes and concentrations
Severe Water Loss
inadequate water consumption
physiologic mechanisms (ADH and renin secretion)
behavioral changes (increasing fluid intake)
Bleeding (GI bleeding, Trauma)
Dialysis (Hemodialysis/Peritoneal dialysis)
GI (Diarrhoea, Vomiting, Nasogastric suction)
Skin (Burns, Excessive sweating, Exfoliation)
3rd-space losses (Intestinal lumen, Intraperitoneal, Retroperitoneal)
Renal and Adrenal
Acute renal failure
Adrenal disorders (Adrenal insufficiency (causing adrenal steroid deficiency) including Addison's disease, Hypoaldosteronism)
Osmotic diuresis (Diabetes mellitus with extreme glucosuria)
Diuretics ( Loop diuretics, Thiazide diuretics)
Salt-wasting renal disease ( Interstitial nephritis, Medullary cystic disease, Myeloma (occasionally), Pyelonephritis (occasionally)
In mild volume depletion (< 5% of ECF), the only sign may be diminished skin turgor (Skin turgor may be low in elderly patients regardless of volume status)
Dry mucous membranes do not always correlate with volume depletion, especially in the elderly and in mouth-breathers
5-10% of ECF (orthostatic tachycardia, orthostatic hypotension)
more than 10% of ECF
signs of shock (tachypnea, tachycardia, hypotension, confusion, poor capillary refill)
plasma electrolytes, BUN, and creatinine.
Rarely plasma osmolality and urine chemistries
Rarely central venous pressure and pulmonary artery occlusion pressure
During volume depletion, normally functioning kidneys conserve Na. Thus, the urine Na concentration is usually < 15 mEq/L; urine osmolality is often > 450 mOsm/kg.
Misleadingly high urinary Na (generally > 20 mEq/L) or low urine osmolality can also occur due to renal Na losses resulting from renal disease, diuretics, or adrenal insufficiency.
Mild-to-moderate volume deficits may be replaced by increased oral intake of Na and water when patients are conscious and not vomiting
When volume deficits are severe or when oral fluid replacement is impractical, IV 0.9% saline is given
If water is gained, but electrolytes are not:
ECF volume increases, ECF becomes hypotonic to ICF, fluid shifts from ECF to ICF. may result in overrhydration: (distorts cells, changes solute concentrations around enzymes, disrupts normal cell functions)
If water is gained, but electrolytes are not: ECF is at lower concentration, higher volume. Triggers decrease in ADH release, fluid is lost and ICF will lose some water back to ECF, restoring both volume and concentration balance
Increase in total body Na. It increases osmolality, which triggers compensatory mechanisms that produce water retention. When sufficient fluid accumulates in the ECF (usually > 2.5 L), edema develops
Heart failure, Cirrhosis, Renal failure, Nephrotic syndrome, Pregnancy
Edema (Anasarca - severe generalized edema)
Pulmonary edema (Chest x-ray, ABGs, echocardiogram)
Correct the cause
Pulmonary edema ( Oxygen, Nitrates, Morphine, Ventilatory assistance as needed)
Decreased TBW and Na, with a relatively greater decrease in Na:
GI: Diarrhea, Vomiting
3rd-space: Burns, Pancreatitis, Peritonitis, Rhabdomyolysis, Small-bowel obstruction.
Renal losses: Diuretics, Mineralocorticoid deficiency, Osmotic diuresis (glucose, urea, mannitol), Salt-losing nephropathies (eg, interstitial nephritis, partial urinary tract obstruction, and polycystic kidney disease)
both plasma osmolality and blood volume decrease. ADH secretion increases despite a decrease in osmolality to maintain blood volume. The resulting water retention increases plasma dilution and hyponatremia.
Increased TBW with near-normal total body Na:
Drugs: Diuretics, barbiturates, carbamazepine, opioids, cyclophosphamide NSAIDs, oxytocin
Disorders: Adrenal insufficiency as in Addison's disease, Hypothyroidism, Syndrome of inappropriate ADH secretion
Increased intake of fluids: Primary polydipsia
States that increase nonosmotic release of ADH: Emotional stress, Pain, Postoperative states
Increased total body Na with a relatively greater increase in TBW:
Extrarenal disorders: Cirrhosis, Heart failure
Renal disorders: Acute kidney dysfunction, Chronic kidney disease, Nephrotic syndrome
Syndrome of Inappropriate ADH Secretion (SIADH)
excessive ADH release.
less-than-maximally-dilute urine in the presence of plasma hypo-osmolality (hyponatremia) without volume depletion or overload, emotional stress, pain, diuretics, or other drugs that stimulate ADH secretion in patients with normal cardiac, hepatic, renal, adrenal, and thyroid function.
associated with myriad disorders
Disorders Associated with SIADH
Cancer: CNS, Duodenum, Lung, Lymphoma, Pancreas.
CNS disorders: Acute intermittent porphyria, Acute psychosis, Brain abscess, Encephalitis, Guillain-Barré syndrome, Head trauma, Meningiti, Stroke, Subdural or subarachnoid hemorrhage.
Endocrine: Addison's disease, Hypopituitarism, Hypothyroidism
Pulmonary: Aspergillosis, Lung abscess, Pneumonia, TB
Miscellaneous: Protein-energy undernutrition, Surgery
mainly involve CNS dysfunction (brain swelling). However, when hyponatremia is accompanied by disturbances in total body Na content, signs of ECF volume depletion or overload also occur
older chronically ill patients with hyponatremia develop more symptoms than younger otherwise healthy patients
Symptoms are more severe with acute hyponatremia (<24h)
occur when the effective plasma osmolality falls to < 240 mOsm/kg
consist mainly of changes in mental status: altered personality, Lethargy, confusion
Severe hyponatremia (< 115 mEq/L): Stupor, Neuromuscular hyperexcitability, Hyperreflexia, Seizures, Coma, Death
Plasma and urine electrolytes and serum osmolality, urine osmolality.
Clinical assessment of volume status.
TSH, freeT4,and cortisol levels
Plasma Na may be low when severe hyperglycemia increases osmolality and water moves out of cells into the ECF. Plasma Na concentration falls about 1.6 mEq/L for every 100-mg/dL (5.55-mmol/L) rise in the plasma glucose concentration above normal.
Pseudohyponatremia with normal plasma osmolality may occur in hyperlipidemia or extreme hyperproteinemia, because the lipid or protein occupies space in the volume of plasma taken for analysis; the concentration of Na in plasma itself is not affected.
Laboratory tests should include plasma and urine osmolality and electrolytes. Euvolemic patients should also have thyroid and adrenal function tested. Hypo-osmolality in euvolemic patients should cause excretion of a large volume of dilute urine (eg, osmolality < 100 mOsm/kg and specific gravity< 1.003).
Plasma Na concentration and plasma osmolality that are low and urine osmolality that is inappropriately high (120 to 150 mmol/L) with respect to the low plasma osmolality suggest volume overload, volume contraction, or SIADH. Volume overload and volume contraction are differentiated clinically When neither volume overload or volume contraction appears likely, SIADH is considered.
Patients with SIADH are usually euvolemic or slightly hypervolemic. BUN and creatinine values are normal, and serum uric acid is generally low. Urine Na concentration is usually > 30 mmol/L, and fractional excretion of Na is > 1%
patients with hypovolemia and normal renal function, Na reabsorption results in a urine Na of < 20 mmol/L. Urine Na > 20 mmol/L in hypovolemic patients suggests mineralocorticoid deficiency or salt-losing nephropathy.
Hyperkalemia suggests adrenal insufficiency
Rapid correction of hyponatremia, even mild hyponatremia, risks neurologic complications
Except possibly in the first few hours of treatment of severe hyponatremia, Na should be corrected no faster than 0.5 mEq/L/h
Even with severe hyponatremia, increase in plasma Na concentration should not exceed 10 mEq/L over the first 24 h
monitor urine output frequently: high output of dilute urine is the rst sign of dangerously rapid correction of hyponatremia
-asymptomatic hyponatremia (ie, plasma Na > 120 mEq/L): elimination of the diuretic, some patients need some Na or K replacement
-With hypovolemia and normal adrenal function: 0.9% saline, When intravascular volume is normalized then restriction of free water ingestion to ≤ 500 to 1000 mL/24 h may be needed
-in whom hyponatremia is due to renal Na retention (eg, heart failure, cirrhosis, nephrotic syndrome) and dilution, water restriction combined with treatment of the underlying disorder is required
-In other patients in whom simple fluid restriction is ineffective, a loop diuretic in escalating doses can be used, sometimes in conjunction with IV 0.9% normal saline.
-K and other electrolytes lost in the urine must be replaced
-When hyponatremia is more severe and unresponsive to diuretics, intermittent or continuous hemofiltration may be needed to control ECF volume while hyponatremia is corrected with IV 0.9% normal saline
-In euvolemia, treatment is directed at the cause (eg, hypothyroidism, adrenal insufficiency, diuretic use).
-When SIADH is present, severe water restriction (eg, 250 to 500 mL/24 h) is generally required. Additionally, a loop diuretic may be combined with IV 0.9% saline.
-plasma Na < 109 mEq/L; effective osmolality < 238 mOsm/kg
-Severe hyponatremia in asymptomatic patients can be treated safely with stringent restriction of water intake
-Hyponatremia in patients with neurologic symptoms supplementation of sodium is needed
-plasma Na be raised no faster than 1 mEq/L/h, but replacement rates of up to 2 mEq/L/h for the first 2 to 3 h have been suggested for patients with seizures.
-Hypertonic saline may be used, but only with frequent electrolyte determinations
-The rise should be ≤ 10 mEq/L over the first 24 h. More vigorous correction risks precipitation of osmotic demyelination syndrome.
Osmotic demyelination syndrome
may follow too-rapid correction of hyponatremia.
Demyelination may affect the pons and other areas of the brain.
Lesions are more common in patients with alcoholism, undernutrition, or other chronic debilitating illness.
Flaccid paralysis, dysarthria, and dysphagia can evolve over a few days or weeks.
The lesion may extend dorsally to involve sensory tracts and leave patients with a locked-in syndrome (an awake and sentient state in which patients, because of generalized motor paralysis, cannot communicate, except possibly by coded eye movements).
Damage often is permanent.
When Na is replaced too rapidly (eg, > 14 mEq/L/8 h) and neurologic symptoms start to develop, it is critical to prevent further plasma Na increases by stopping hypertonic fluids
Decrease in plasma Na concentration < 136 mEq/L caused by an excess of water relative to solute
can be associated with hypo-osmolality (most common),(<280 mOsm/kg), iso-osmolality(280-295 mOsm/kg), or hyperosmolality (>295 mOsm/kg)
plasma Na concentration > 145 mEq/L
reflects a deficit of total body water (TBW) relative to total body Na content. Because total body Na content is reflected by ECF volume status, hypernatremia must be considered along with status of the ECF volume: hypovolemia, euvolemia, and hypervolemia.
Decreased TBW and Na with a relatively greater decrease in TBW
-GI losses: Diarrhea, Vomiting
-Skin losses: Burns, Excessive sweating
-Renal losses: Intrinsic renal disease, Loop diuretics, Osmotic diuresis (glucose, urea, mannitol)
Because glucose does not penetrate cells in the absence of insulin, hyperglycemia further dehydrates the ICF compartment. The degree of hyperosmolality in hyperglycemia may be obscured by the lowering of plasma Na resulting from movement of water out of cells into the ECF
Decreased TBW with near-normal total body Na
-Extrarenal losses from respiratory tract: Tachypnea
-Extrarenal losses from skin: Excessive sweating, Fever
-Renal losses: Central diabetes insipidus, Nephrogenic diabetes insipidus
-Other: Inability to access water, Primary hypodipsia, Reset osmostat
Increased Na with normal or increased TBW
-Hypertonic fluid administration: Hypertonic saline, NaHCO3
-Mineralocorticoid excess: Adrenal tumors secreting deoxycorticosterone, Congenital adrenal hyperplasia
Hypernatremia in the elderly
common in the elderly, particularly postoperative patients and those receiving tube feedings or parenteral nutrition.
Other contributing factors may include the following:
Dependence on others to obtain water
Impaired thirst mechanism
Impaired renal concentrating capacity (due to diuretics, impaired ADH release, or nephron loss accompanying aging or other renal disease)
Impaired angiotensin II production (which may contribute directly to the impaired thirst mechanism)
The major symptom of hypernatremia is thirst. The absence of thirst in conscious patients with hypernatremia suggests an impaired thirst mechanism.
The major signs of hypernatremia result from CNS dysfunction due to brain cell shrinkage:
Confusion, neuromuscular excitability, Hyperreflexia, Seizures, Coma
Cerebrovascular damage with subcortical or subarachnoid hemorrhage and venous thromboses are common in patients who died from severe hypernatremia
In chronic hypernatremia, osmotically active substances occur in CNS cells (idiogenic osmoles) and increase intracellular osmolality. Therefore, the degree of brain cell dehydration and resultant CNS symptoms are less severe in chronic than in acute hypernatremia.
When hypernatremia occurs with abnormal total body Na, the typical symptoms of volume depletion or overload are present
Plasma Na, water deprivation test
Replacement of intravascular volume and of free water (oral or intravenous)
Acute hypernatremia (< 24 h) should be corrected within 24 h
chronic or of unknown duration hypernatremia should be corrected over 48 h
plasma osmolality should be lowered at a rate of no faster than 2 mOsm/L/h to avoid cerebral edema caused by excess brain solute
Free water deficit = TBW × [(plasma Na/140) − 1]
TBW (total body water) = weight x 0.6
In patients with hypernatremia and ECF volume overload the free water deficit can be replaced with 5% glucose, which can be supplemented with a loop diuretic.
Other electrolytes, including plasma K, should be monitored and should be replaced as needed
In patients with hypernatremia and euvolemia, free water can be replaced using either 5% glucose or 0.45% saline
In patients with hypernatremia and hypovolemia, particularly in patients with diabetes with nonketotic hyperglycemic coma, 0.45% saline can be given as an alternative to a combination of 0.9% normal saline and 5% glucose to replenish Na and free water.
Alternatively, ECF volume and free water can be replaced separately, using the formula given previously to estimate the free water deficit.
When severe acidosis (pH < 7.10) is present, NaHCO3 solution can be added to 5% glucose or 0.45% saline, as long as the final solution remains hypotonic