Fluid Balance and Osmolality

Hyponatremia and Hypernatremia

• Hyponatremia is defined as a serum sodium (Na+) concentration less than 135 mmol/L.
• Hypernatremia is defined as a serum sodium (Na+) concentration greater than 145 mmol/L.
• Normal plasma osmolality is 275-290 mosmol/kg
• Osmolality formula = 2(Na+) + 2(K+) + Glucose + Urea
• Sodium is a key determinant of osmolality and fluid balance.
• Hyponatremia = too much water
• Hypernatremia = too little water
• Total body water (TBW) is 60% of weight in men, 50% in women

Total Body Water (TBW)

• TBW consists of two main compartments: extracellular fluid (ECF) and intracellular fluid (ICF).
• Cell membranes allow the passage of water but not electrolytes.
• In normal adults, ECF volume is approximately 33-40% of TBW.
• ECF volume is determined by sodium and water content in ECF.
• Rest of TBW (67%) is in cells.
• Regulation of ECF volume is mediated by urinary sodium excretion, controlled by renin-angiotensin-aldosterone and sympathetic systems for sodium retention.
• Natriuretic peptides promote sodium excretion.

Plasma Osmolality

• Plasma osmolality is a measure of solute concentration in plasma.
• It's determined by the ratio of plasma solutes to plasma water.
• Primarily influenced by sodium salts, with contributions from potassium, calcium, glucose, and urea.
• Glucose and urea have a significant impact on plasma osmolality when markedly elevated as in uncontrolled diabetes or reduced kidney function.
• Plasma and ECF osmolalities are similar to intracellular osmolality due to water permeability of cell membranes.

Role of Sodium in the Body

• Extreme variation in osmolarity causes cells to shrink or swell, damaging or destroying cellular structure.
• The overall mass of Na+ is under aldosterone regulation (manipulates Na+ retention in the kidney).
• The Na+ concentration in plasma is under antidiuretic hormone (ADH) regulation (manipulates H20 retention in the kidney).
• Low Na+ concentrations do not necessarily mean that total Na+ mass is low, particularly in chronic heart failure. Osmolarity can be low but Na+ mass can be high because of excess water in the ECF.

Summary of Sodium Homeostasis

• Involves afferent and efferent pathways with the central nervous system.
• Sensitive to volaemic changes in the vascular baroreceptors.
• Angiotensinogen, renin, angiotensin I, ACE, angiotensin II, aldosterone, AVP(antidiuretic hormone), and natriuretic peptides are mechanisms involved.

Pathophysiology

• Body osmolality and fluid volume are regulated by different mechanisms.
• Osmoreceptors in hypothalamus detect rises in osmolality and release ADH.
• Baroreceptors assess vascular fullness or total body water.
• Osmoreceptors and baroreceptors work in a tug-of-war to regulate water content.
• Intake is regulated by thirst, and output by the kidneys.
• ADH (antidiuretic hormone)/AVP directly regulates water excretion by the kidneys, stimulating insertion of aquaporins into the cell membrane of collecting ducts. This increases water reabsorption and concentration of excreted urine.
• Other factors influencing ADH release include angiotensin II, natriuretics, and ethanol.

Hyponatremia

• Acute hyponatremia symptoms include nausea, malaise, headache, lethargy, obtundation, seizures, coma.
• Chronic hyponatremia symptoms include fatigue, nausea, dizziness, gait disturbances, forgetfulness, confusion, lethargy, and muscle cramps.
• Neurological signs may include altered mental status, hypothermia, hyperreflexia, and signs of brain herniation (severe cases).
• Osmotic injury to neurons causes confusion, lethargy, headaches, coma, seizures.

Influence of Cause and Volume Status

• Specific symptoms and signs depend on underlying cause (water retention, solute loss) and patient's volume status.
• Assess volume status- hypovolaemic, euvolaemic, hypervolaemic status.

Signs and Symptoms Due to Hypovolemia

• Dry mucous membranes
• Reduced skin turgor
• Orthostatic hypotension
• Reduced urine output
• Concentrated urine
• Skin with decreased turgor which remains elevated after being pulled up and released

Signs and Symptoms Due to Hypervolemia

• Ascites
• Peripheral/leg edema
• Puffy facial features (nephrotic syndrome)
• Raised JVP (jugular venous pressure)
• S3 heart sound
• Bi-basal crackles on lung auscultation
• Breathlessness

SIADH (Syndrome of Inappropriate ADH)

• Osmoreceptors in the hypothalamus detect changes in sodium levels (osmolality).
• ADH release occurs when sodium levels are high or blood volume is low.
• Low blood volume can arise from actual fluid loss (dehydration) or apparent fluid loss (e.g., congestive heart failure).
• ADH causes the kidneys to reabsorb water and reduces urine output leading to hyponatremia due to excess water retention diluting the sodium concentration in the blood.

SIADH: Clinical Presentation and Management

• SIADH should be suspected in patients with hyponatremia, hypoosmolality, and urine osmolality above 100 mosmol/kg
• Management includes fluid restriction and addressing the underlying cause.

Less Common Causes of Hyponatremia

• Beer potomania (excessive beer drinking, low solute intake)
• Tea and toast syndrome (low solute diet, inability to cook)
• Primary psychogenic polydipsia (abnormal thirst)

Differential Diagnosis of Hyponatremia

• Hypovolaemic, euvolaemic, hypervolaemic
• Medications (e.g., diuretics, ACEi, ARBs, SSRIs, opioids)
• GI losses, Addisonian Crisis
• Mineralocorticoid deficiency, Glucocorticoid deficiency
• SIADH (Syndrome of Inappropriate Antidiuretic Hormone)
• Hypothyroidism
• AKI (Acute Kidney Injury) or CKD (Chronic Kidney Disease)
• CCF (Congestive Cardiac Failure)
• Cirrhosis
• Nephrotic syndrome

Investigations for Hyponatremia

• Assess the degree of hyponatremia in serum.
• Assess for symptoms (Symptomatic or Asymptomatic/mild).
• Assess serum osmolarity (Normal, Low, or High)
• Assess volume status (Hypovolaemic, Euvolaemic, or Hypervolaemic)
• Determine relevant blood tests, urinary tests, imaging.

Hypernatremia

• Hypernatremia occurs when there's a high concentration of sodium in the blood.
• Pathogenesis arises from water loss exceeding water intake or salt intake exceeding water intake.
• Causes include inadequate fluid intake, excessive fluid loss (sweat, urine, diarrhea), & diabetes insipidus, salt overload.
• Clinical presentation includes Thirst, weakness, lethargy, seizures, and coma (severe cases)
• Diagnosis is typically based on serum sodium levels, urine osmolality, and sodium levels to help determine the cause.
• Treatment involves controlled water replacement and addressing the underlying cause in severe cases.

Treatment for Severe Hyponatremia

• Decision to treat is based on symptoms (not number); cerebral irritation, nausea, confusion, headache, vomiting, drowsiness, seizures, coma
• If patient is unconscious or having seizures, mortality is 60-90%
• Administration of hypertonic saline 3% (100ml bolus over 10-15 minutes)
• Aim to raise Na by 3-5mmol over 4 hours

Osmotic Demyelination Syndrome

• A neurological disorder caused by rapid correction of hyponatremia.
• Occurs due to rapid shift in brain solute concentration affecting brain cell integrity.
• Symptoms include difficulty speaking, swallowing, movement disorders, seizures, altered consciousness.
• Risk factors include chronic, severe hyponatremia (serum sodium <120 mEq/L) present for more than two days.
• Diagnosis via brain MRI showing characteristic changes

Diabetes Insipidus

• Disorder of impaired water excretion caused by excess of antidiuretic hormone (ADH).
• Characterized by a euvolemic hypotonic hyponatremia.
• Pathophysiology: ADH secretion leads to concentrated urine and reduced urine volume, which fails to suppress leading to continued water retention, diluting plasma sodium concentration.
• Mechanisms include; Cranial/Central Diabetes Insipidus and Nephrogenic Diabetes Insipidus.

Differentiating SIADH vs DI

• SIADH presents with hyponatremia, oliguria, concentrated urine, volume overload, decreased serum osmolality and increased urinary osmolality
• DI presents with hypernatremia, polyuria, dilute urine, Dehydration, Increased serum osmolality and decreased urinary osmolality

Hypernatremia: Investigations

• Serum Osmolality: Compare with urine osmolality (normal serum, low urine suggests DI).
• Electrolytes: High Na+, low K+ suggest GI losses.
• Glucose: suggest osmotic diuresis in diabetes.
• Ketones: in diabetic ketoacidosis.
• Urinary testing: assess urine osmolality, look for low values suggesting DI. A 24-hour urine collection can also assist with this diagnosis
• Imaging: Assess pituitary mass or cranial mass via MRI.

Hypernatremia: Treatment

• Calculate free water deficit: 0.6 x kg x [(serum Na – 140)/140].
• Replace 7.7 L in addition to 2 litres, dividing it over days.
• Fluid options include 5% dextrose, 0.45% NaCl.
• Treatment for Central DI: DDAVP (desmopressin) – synthetic ADH, Nephrogenic DI won't respond.

Key Points

• Hyponatremia is common (1 in 5 inpatients).
• Assess fluid status in hyponatremia to determine differential diagnosis.
• Consider common causes first for hypernatremia and then rarer ones like DI.