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Fluid and Electrolyte Disturbances

Hao, Chuan-Ming MD

Huashan Hospital

Water and electrolytes disturbances

• Sodium balance

– Hypovolemia

• Water balance

– Hyponatremia

– Hypernatremia

• Potassium balance

– Hypokelemia

– hyperkelemia

Composition of Body Fluids

• Water is the most abundant constituent in the body:

– 50% of body weight in women

– 60% in men

• Total body water is distributed in two major compartments:

– 55–75% is intracellular fluid (ICF)

– 25–45% is extracellular fluid (ECF)

• ECF is subdivided into

– intravascular (plasma water) and

– extravascular (interstitial) spaces in a ratio of 1:3.

2/3 ECF

1/3 ECF

Osmoles

• The major ECF particles: Na+, Cl– and HCO3–

• The predominant ICF osmoles: K+ and organic phosphate esters (ATP, creatine phosphate, and phospholipids)

• Certain solutes, particularly urea, do not contribute to water shifts across most membranes and are thus known as ineffective osmoles.

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Water and electrolytes disturbances

• Sodium balance

– Hypovolemia

• Water balance

– Hyponatremia

– Hypernatremia

• Potassium balance

– Hypokelemia

– hyperkelemia

Sodium Balance

• In the steady state, urinary excretion of sodium is closely matched to dietary salt intake.

• This balance depends on:

• Afferent mechanisms that sense the volume of the ECF compartment relative to its capacitance

• Effector mechanisms that modify the rate of renal sodium excretion

Hypovolemia

• A reduction in the volume of the ECF compartment in relation to its capacitance.

• absolute hypovolemia, a deficit in sodium reflects negative sodium balance.

• The volume of the ECF intravascular and extravascular (interstitial) subcompartments may vary in the same or opposite directions.

• ICF volume is reflected by plasma osmolality and sodium concentration and may be concomitantly disturbed

Causes of hypovolemia

Clinical features

• History: vomiting, diarrhea, trauma…

• Symptoms: Thirst, postural dizziness, oliguria, cyanosis,

• Signs of intravascular volume contraction: – decreased jugular venous pressure,

– postural hypotension,

– postural tachycardia

• Large and more acute fluid losses lead to hypovolemic shock: hypotension, – tachycardia,

– peripheral vasoconstriction and

– hypoperfusion: (cyanosis, cold and clammy extremities, oliguria and altered mental status)

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Diagnosis

• History & physical examination

• Labs:

– BUN, SCr, BUN/SCr (>20)

– UNa <20 mmol/L (exception: ATN, Vomiting),

– UCl < 20 mmol/L (GI)

Treatment

• Goal: restore normovolumia

• Mild volume contraction: oral route

• Severe hypovolemia: IV

Water and electrolytes disturbances

• Sodium balance

– Hypovolemia

• Water balance

– Hyponatremia

– Hypernatremia

• Potassium balance

– Hypokelemia

– hyperkelemia

Water Balance • Disorders of water homeostasis result

in hypo- or hypernatremia

• Water balance is regulated mainly by thirst and urine concentration mechanism

• The principal determinant of renal water excretion is AVP

• Maximal urine osmolality: 1200 mosmol/kg

• Minimal urine osmolality: 50 mosmo/kg

• Normally about 600 mosmols must be excreted per day

• Filtration

• Active Na, Cl reabsorption in TAL

• AVP

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AVP

• AVP secretion:

– systemic osmolality, threshold level of 285 mosmol/kg.

– blood volume and blood pressure.

• Nonosmotic stimul: nausea, intracerebral angiotensin II, serotonin, and multiple drugs.

• Half-life in the circulation: 10–20 min

AVP

• AVP secretion:

– systemic osmolality, threshold level of 285 mosmol/kg.

– blood volume and blood pressure.

• Nonosmotic stimul: nausea, intracerebral angiotensin II, serotonin, and multiple drugs.

• Half-life in the circulation: 10–20 min

Hyponatremia

• Plasma sodium concentration less than 135 mmol/L,

• The most frequently encountered electrolyte abnormality in hospitalized patients.

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• Hypertonic hyponatremia: an accumulation in the ECF compartment of non-sodium-containing effective solutes such as

– very high concentrations of glucose in diabetic patients or

– exogenously administered mannitol or glycerol.

• Isotonic hyponatremia: hyperlipidemia or marked hyperglobulinemia – pseudohyponatremia

• True hypotonic hyponatremia:

– an important underlying disorder that leads to abnormal body water balance,

– the hypotonic state indicates either past or ongoing

expansion of ICF volume.

Hypo-osmolar Disorders

• Depletion:

– Primary Decreases in Total Body Solute + Secondary Water Retention

• Dilution:

– Primary Increases in Total Body Water ± Secondary Solute Depletion

Causes of SIADH

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Clinical features

• Clinical manifestations are related to osmotic water shift leading to increased ICF, specifically brain swell or cerebral edema. Therefore, the symptoms are primarily neurologic and their severity is dependent on the rapidity of onset and absolute decrease in plasma [Na+].

• Symptoms include headache, lethargy, seizures, and a progressively decreased level of consciousness that can progress to coma and death.

• The severity of these neurologic manifestations depends more on the rate of the hypotonic decline in plasma sodium concentration.

• If a patient survives the acute hyponatremia, osmotic adaptation tends to mitigate the symptoms of cerebral edema.

Treatment

• Treatment of hyponatremia varies depending on the category and underlying diagnosis

• It is the importance of identifying and treating any underlying disorder

• The sodium concentration and the rate of correction should be guided by the patient’s age, gender, neurologic status, and any information about recent past plasma sodium concentrations or osmolality values

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• Delayed correction of hyponatremia can perpetuate cerebral edema and result in irreversible neurologic damage and death.

• In contrast, too rapid correction can result in the osmotic demyelination syndrome, which can be fatal, and recovery in nonfatal cases is either slow or incomplete, often with irreversible residual neurologic sequelae

Acute Hypotonic Hyponatremia (<24 to 48 hours)

• If patient is accompanied by severe neurologic symptoms such as seizures or decreased level of consciousness, correction should be rapid and should reach a target sodium concentration.

• The desired rise in sodium concentration should not exceed 2 mmol/L/hour, and the total increase in sodium concentration during the first 12 to 24 hours of treatment should not exceed 12 mmol/L.

Chronic Hyponatremia

• In such cases, the targeted rate of increase in sodium concentration should not exceed 0.5 mmol/L/hour, and the total rise in sodium concentration should not exceed 8 mmol/L in the first 24 hours

• Water restriction is helpful in euvolemic patients

Normovolemic hyponatremia

• In patients with normovolemic hyponatremia, the appropriate therapeutic approach is to address the underlying disease

• Water restriction

• V2 receptor antagonist

Hypovolemic Hypotonic Hyponatremia

• When hypovolemia is clearly evident, administration of volume repletion in the form of isotonic saline is the treatment of choice – appropriate clinical history,

– orthostatic hypotension,

– low urine sodium concentration in the setting of extrarenal fluid losses,

– elevated plasma urea and uric acid concentrations

• Great caution should be exercised in the administration of isotonic saline to these patients because sometimes the administration of small volumes of isotonic saline can induce a brisk and rapid decrease in urine osmolality

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Treatment

• Treat the underlying disease, if possible.

• Fluid restriction.

• Oral or intravenous sodium chloride in patients with true volume depletion.

• Sodium chloride administration is also effective in patients the syndrome of inappropriate antidiuretic hormone secretion (SIADH) using either oral salt tablets or hypertonic saline.

• In contrast, isotonic saline is often not effective and may worsen the hyponatremia in SIADH

• Administration of a vasopressin receptor antagonist

Hypernatremia

• Hypernatremia, defined as a plasma sodium concentration greater than 144 mmol/L, always reflects a state of hypertonicity.

Causes of Hypernatremia

• Hypovolemia: associated with low total body sodium – losses of both Na+ and water, but with a relatively greater loss of

water

• Hypervolemia: associated with increased total body sodium – administration of hypertonic solutions such as 3% NaCl, NaHCO3.

– Therapeutic hypernatremia: hypertonic saline solutions have emerged as a preferable alternative to mannitol for treatment of increased intracranial pressure.

• Euvolemia: associated with normal body sodium – Most patients with hypernatremia secondary to water loss appear

euvolemic with normal total body Na+ because loss of water without Na+ does not lead to overt volume contraction

Diabetes insipidus (DI)

• Characterized by polyuria and polydipsia

• Caused by defects in vasopressin action.

• Patients with central and nephrogenic DI and primary polydipsia present with polyuria and polydipsia.

• The differentiation between these entities can be accomplished by clinical evaluation, with measurements of – vasopressin levels and

– the response to a water deprivation test followed by vasopressin administration

• Central Diabetes Insipidus

• Congenital Nephrogenic Diabetes Insipidus

• Acquired Nephrogenic Diabetes Insipidus

Clinical Manifestations

• Signs and symptoms mostly relate to the CNS and include altered mental status, lethargy, irritability, restlessness, seizures (usually in children), muscle twitching, hyperreflexia, and spasticity.

• Fever, nausea or vomiting, labored breathing, and intense thirst can also occur.

• In adults, serum Na+ concentrations above 160 mmol/l are associated with a 75% mortality, although this may reflect associated comorbidities rather than hypernatremia per se

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Treatment of Hypernatremia

• Hypernatremia occurs in predictable clinical settings, allowing opportunities for prevention

– recovery from acute kidney injury,

– catabolic states,

– therapy with hypertonic solutions,

– uncontrolled diabetes

– burns

• Water deficit should be corrected slowly over 48 – 72h. The plasma Na concentration be lowered by 0.5 mmol/l/h and by no more than 12 mmol/L over the 1st 24h

• Route: mouth or via a nasogastric tube or 5% dextrose or half-isotonic saline iv

• CDI

– Desmopressin

– Low salt diet + low-dose thiazide diuretics

– Drugs that stimulate AVP section or enhance its action

Water and electrolytes disturbances

• Sodium balance

– Hypovolemia

• Water balance

– Hyponatremia

– Hypernatremia

• Potassium balance

– Hypokelemia

– hyperkelemia

Potassium balance

• K intake: 1 mmol/kg/d

• Immediately following a meal, most K enter cells (plasma K, insulin, catecholamine)

• Steady state, K ingestion matches with excretion

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Potassium excretion • The filtered K is 10 -20 fold of ECF

K content

• 90% of filtered K is reabsorbed in proximal tubule and loop of Henle

• K delivery to distal tubule proximate dietary intake

• All regulation of renal K excretion an total body K balance occurs in the distal nephron

• K secretion is regulated by aldosterone and hyperkalemia

• K secretion is facilitated by increased distal Na delivery

High sodium delivery and high levels of aldo

Hypokalemia

Hypokalemia versus Potassium Deficiency

• Potassium deficiency is the state that results from a persistent negative potassium balance

• Hypokalemia refers to a low plasma [K+].

• Hypokalemia can result from potassium deficiency (inadequate potassium intake or excessive potassium losses) or from a net shift of K+ from the ECF to the ICF compartment.

• A patient may have severe potassium depletion without manifesting hypokalemia (diabetes ketoacidosis)

Etiology

• Redistribution

• Increased net loss:

– extrarenal potassium loss

– renal potassium loss

• Decreased net intake

• Pseudohypokalemia

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Redistribution into Cells

• Metabolic alkalosis

• Insulin (diabetic ketoacidosis)

• Stress-induced catecholamine/Beta2 agonist

• Hypokalemic periodic paralysis – genetic defect in a

dihydropyridine-sensitive calcium channel

– hyperthyroidism

• Anabolic states

Non-renal Loss of K

• Excessive sweating

• Diarrhea

• Vomiting or gastric suction

– metabolic alkalosis

– the intravascular volume depletion result in secondary hyperaldosteronism

NaHCO3

Renal loss of K

1. Increased collecting duct Na reabsorption

2. Volume expansion

3. Increased K section

Renal loss of K

Clinical Features

• Hypokalemia may produce electrocardiographic (ECG) abnormalities: including a flattened T wave and a U wave

• Severe hypokalemia is associated with variable degrees of skeletal muscle weakness, even to the point of paralysis

• On rare occasions, diaphragmatic paralysis from hypokalemia can lead to respiratory arrest

• There may also be decreased motility of smooth muscle, manifesting with ileus or urinary retention

• Rarely, severe hypokalemia can result in rhabdomyolysis

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Treatment • The primary short-term risks are cardiovascular arrhythmias

and neuromuscular symptoms.

• Conditions requiring urgent therapy are rare. The clearest indications are – hypokalemic periodic paralysis,

– severe hypokalemia in a patient requiring urgent surgery

– acute myocardial infarction in the patient with significant ventricular ectopy

• Severe hypokalemia or those unable to take anything by mouth require IV replacement – Maximum concentration: 40 mmol/L via peripheral vein or 60 mmol/L

via a central vein

– The rate of infusion should not exceed 20 mmol/h unless paralysis or malignant ventricular arrhythmias are present

Hyperkalemia

Etiology

• Pseudohyperkalemia

• Redistribution – severe hyperglycemia (due to effects of osmolarity)

– severe nonorganic acidosis

– β-blockers.

– Hyperkalemic peroidic paralysis

• Excess Intake – if renal potassium excretion is impaired, for example, by drugs or renal

impairment

• Renal failure

• Impaired Renal Potassium Secretion – chronic hyperkalemia is difficult to produce unless renal potassium

secretion is impaired.

– Factors that affect renal potassium excretion are classified into those due to

• reduced nephron number and

• those due to intrinsic impairment of renal potassium handling.

– In the absence of other contributing factors, renal potassium excretion is moderately well preserved until GFR is reduced to 10 to 20 ml/min. However, both CKD and acute kidney injury (AKI) limit maximal renal potassium excretion.

– Obstructive uropathy leads frequently to hyperkalemia, due to decreased Na+,K+-ATPase expression and activity. In many cases, the hyperkalemia may persist for weeks after relief of the obstruction.

• Specific Medicines – The renin-angiotensin-aldosterone

– medications that inhibit potassium secretion

• Intrinsic Renal Defect

– pseudohypoaldosteronism type 2, ( Gordon’s syndrome) • hypertension, hyperkalemia, metabolic acidosis, and normal GFR

• Mutations in WNK1 or WNK4, increase sodium absorption and inhibit potassium secretion in the distal convoluted tubule and collecting duct

Clinical manifestation

• Hyperkalemia may be asymptomatic but still life-threatening

• The most prominent effect of hyperkalemia is alteration of cardiac conduction. This is demonstrable on the ECG.

• Hyperkalemia also affects muscle contraction. – weakness

– severe hyperkalemia, respiratory failure may occur from paralysis of the diaphragm.

• Metabolic acidosis: hyperkalemia inhibits renal ammoniagenesis

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Diagnosis

• If the etiology is not readily apparent and the patient is asymptomatic, pseudohyperkalemia should be excluded

• Medications that impair K handling and sources of K intake

• The severity of hyperkalemia is determined by

– Symptoms

– Plasma K concentration

– ECG

Treatment

• Approach to therapy depends on the degree of hyperkalemia as determined by

– Plasma K concentration

– Muscular weakness

– ECG

• Severe hyperkalemia requires emergent treatment

– Minimizing membrane depolarization

– Shifting K into cells

– Promoting K loss