Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

Antidiuretic Hormone (ADH)

Source

• Synthesized in the hypothalamus Hypothalamus The hypothalamus is a collection of various nuclei within the diencephalon in the center of the brain. The hypothalamus plays a vital role in endocrine regulation as the primary regulator of the pituitary gland, and it is the major point of integration between the central nervous and endocrine systems. Hypothalamus:
  • Supraoptic nuclei
  • Paraventricular nuclei
• Stored and secreted by the posterior pituitary Pituitary A small, unpaired gland situated in the sella turcica. It is connected to the hypothalamus by a short stalk which is called the infundibulum. Hormones: Overview and Types 

Secreted in response to

• Increased serum osmolarity Osmolarity The concentration of osmotically active particles in solution expressed in terms of osmoles of solute per liter of solution. Osmolality is expressed in terms of osmoles of solute per kilogram of solvent. Hypernatremia:
  • Detected by osmoreceptors Osmoreceptors Renal Sodium and Water Regulation ( hypothalamus Hypothalamus The hypothalamus is a collection of various nuclei within the diencephalon in the center of the brain. The hypothalamus plays a vital role in endocrine regulation as the primary regulator of the pituitary gland, and it is the major point of integration between the central nervous and endocrine systems. Hypothalamus)
  • ADH is very sensitive to osmolality Osmolality Plasma osmolality refers to the combined concentration of all solutes in the blood. Renal Sodium and Water Regulation, responding to as little as a 1% increase.
• Hypovolemia Hypovolemia Sepsis in Children:
  • Detected by baroreceptors Baroreceptors Receptors in the vascular system, particularly the aorta and carotid sinus, which are sensitive to stretch of the vessel walls. Diabetes Insipidus (left atrium, carotid artery, aortic arch Aortic arch Mediastinum and Great Vessels: Anatomy) 
  • Caused by low blood volume or blood pressure
  • ADH is less sensitive to blood pressure and volume, requiring a change of 10%–15% to stimulate its release. 

Function

• Increases free water absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption (via V2 receptors V2 receptors Renal Sodium and Water Regulation)
  • ↓ Serum osmolarity Osmolarity The concentration of osmotically active particles in solution expressed in terms of osmoles of solute per liter of solution. Osmolality is expressed in terms of osmoles of solute per kilogram of solvent. Hypernatremia
  • ↑ Urine osmolarity Osmolarity The concentration of osmotically active particles in solution expressed in terms of osmoles of solute per liter of solution. Osmolality is expressed in terms of osmoles of solute per kilogram of solvent. Hypernatremia 
  • ↑ Intravascular volume 
• Vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure (via V1 receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors)
• Release of von Willebrand’s factor from endothelial cells

Etiology and Pathophysiology

• Acquired SIADH: continuous production of ADH without a proper feedback mechanism control
• Hereditary SIADH:
  • A mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations affects the gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics for the renal V2 receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors
  • Also called nephrogenic syndrome of inappropriate antidiuresis
• Both types cause free-water absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption → dilutional hyponatremia Hyponatremia Hyponatremia is defined as a decreased serum sodium (sNa+) concentration less than 135 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled via antidiuretic hormone (ADH) release from the hypothalamus and by the thirst mechanism. Hyponatremia → cerebral edema Cerebral edema Increased intracellular or extracellular fluid in brain tissue. Cytotoxic brain edema (swelling due to increased intracellular fluid) is indicative of a disturbance in cell metabolism, and is commonly associated with hypoxic or ischemic injuries. An increase in extracellular fluid may be caused by increased brain capillary permeability (vasogenic edema), an osmotic gradient, local blockages in interstitial fluid pathways, or by obstruction of CSF flow (e.g., obstructive hydrocephalus). Increased Intracranial Pressure (ICP) and neurologic symptoms

Clinical Presentation

• Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are usually euvolemic.
• Patient presentation depends on:
  • The rate and severity of hyponatremia Hyponatremia Hyponatremia is defined as a decreased serum sodium (sNa+) concentration less than 135 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled via antidiuretic hormone (ADH) release from the hypothalamus and by the thirst mechanism. Hyponatremia (acute and chronic)
  • The degree of cerebral edema Cerebral edema Increased intracellular or extracellular fluid in brain tissue. Cytotoxic brain edema (swelling due to increased intracellular fluid) is indicative of a disturbance in cell metabolism, and is commonly associated with hypoxic or ischemic injuries. An increase in extracellular fluid may be caused by increased brain capillary permeability (vasogenic edema), an osmotic gradient, local blockages in interstitial fluid pathways, or by obstruction of CSF flow (e.g., obstructive hydrocephalus). Increased Intracranial Pressure (ICP)
• Acute hyponatremia Hyponatremia Hyponatremia is defined as a decreased serum sodium (sNa+) concentration less than 135 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled via antidiuretic hormone (ADH) release from the hypothalamus and by the thirst mechanism. Hyponatremia:
  • Cerebral edema Cerebral edema Increased intracellular or extracellular fluid in brain tissue. Cytotoxic brain edema (swelling due to increased intracellular fluid) is indicative of a disturbance in cell metabolism, and is commonly associated with hypoxic or ischemic injuries. An increase in extracellular fluid may be caused by increased brain capillary permeability (vasogenic edema), an osmotic gradient, local blockages in interstitial fluid pathways, or by obstruction of CSF flow (e.g., obstructive hydrocephalus). Increased Intracranial Pressure (ICP) is the main problem.
  • Symptoms are mostly neurologic and include:
    • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics 
    • Vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
    • Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
    • Brainstem herniation Herniation Omphalocele
    • Coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma
    • Death 
  • Movement of water into cells will stimulate additional ADH secretion Secretion Coagulation Studies.
  • A major complication is hypoxemic respiratory failure Hypoxemic Respiratory Failure Respiratory Failure.
• Chronic hyponatremia Hyponatremia Hyponatremia is defined as a decreased serum sodium (sNa+) concentration less than 135 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled via antidiuretic hormone (ADH) release from the hypothalamus and by the thirst mechanism. Hyponatremia:
  • The cells adapt to the osmotic shift/dilutional hyponatremia Hyponatremia Hyponatremia is defined as a decreased serum sodium (sNa+) concentration less than 135 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled via antidiuretic hormone (ADH) release from the hypothalamus and by the thirst mechanism. Hyponatremia by losing organic osmolytes (inositol, betaine, glutamate Glutamate Derivatives of glutamic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure. Synthesis of Nonessential Amino Acids); therefore, the cerebral edema Cerebral edema Increased intracellular or extracellular fluid in brain tissue. Cytotoxic brain edema (swelling due to increased intracellular fluid) is indicative of a disturbance in cell metabolism, and is commonly associated with hypoxic or ischemic injuries. An increase in extracellular fluid may be caused by increased brain capillary permeability (vasogenic edema), an osmotic gradient, local blockages in interstitial fluid pathways, or by obstruction of CSF flow (e.g., obstructive hydrocephalus). Increased Intracranial Pressure (ICP) will be reduced.
  • Symptoms are subtle, including:
    • Abnormal gait Gait Manner or style of walking. Neurological Examination
    • Confusion
    • Cognitive defects

Diagnosis

• Laboratory results:
  • Serum sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia < 135 mEq/L
  • Serum osmolality Osmolality Plasma osmolality refers to the combined concentration of all solutes in the blood. Renal Sodium and Water Regulation < 280 mOsm/kg
  • Urine sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia > 20–40 mEq/L (unless on a low-sodium diet)
  • Reduced anion gap Anion gap Metabolic Acidosis
  • Urine osmolality Osmolality Plasma osmolality refers to the combined concentration of all solutes in the blood. Renal Sodium and Water Regulation > 100 mOsm/kg
• Further tests should be performed to find the underlying cause according to the history:
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with long-standing smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases history and weight loss Weight loss Decrease in existing body weight. Bariatric Surgery require a chest X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests and/or computed tomography (CT) scan to rule out possible lung cancer Lung cancer Lung cancer is the malignant transformation of lung tissue and the leading cause of cancer-related deaths. The majority of cases are associated with long-term smoking. The disease is generally classified histologically as either small cell lung cancer or non-small cell lung cancer. Symptoms include cough, dyspnea, weight loss, and chest discomfort. Lung Cancer.
  • Creatinine levels to assess renal function

Management

• The underlying cause should be treated if feasible.
• The low levels of sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia ( hyponatremia Hyponatremia Hyponatremia is defined as a decreased serum sodium (sNa+) concentration less than 135 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled via antidiuretic hormone (ADH) release from the hypothalamus and by the thirst mechanism. Hyponatremia) should be corrected:
  • Correction should be done gradually (< 8 mEq/L per 24 hours) to prevent osmotic demyelination Demyelination Multiple Sclerosis syndrome.
  • Fast correction will cause osmotic demyelination Demyelination Multiple Sclerosis syndrome ( dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia, dysarthria Dysarthria Disorders of speech articulation caused by imperfect coordination of pharynx, larynx, tongue, or face muscles. This may result from cranial nerve diseases; neuromuscular diseases; cerebellar diseases; basal ganglia diseases; brain stem diseases; or diseases of the corticobulbar tracts. The cortical language centers are intact in this condition. Wilson Disease, diplopia Diplopia A visual symptom in which a single object is perceived by the visual cortex as two objects rather than one. Disorders associated with this condition include refractive errors; strabismus; oculomotor nerve diseases; trochlear nerve diseases; abducens nerve diseases; and diseases of the brain stem and occipital lobe. Myasthenia Gravis, ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia, ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia, mutism, locked-in syndrome Locked-in syndrome Locked-in syndrome (LIS) is a rare neurological disorder in which patients are awake and conscious but are unable to move their limbs or speak. The disorder is a result of brain injury to the ventral aspect of the pons and caudal ventral midbrain; etiologies include brainstem stroke, tumors, intracranial bleeding, and demyelinating disorders. Locked-in Syndrome).
  • Acute and severe symptoms (e.g., seizure):
    • Hypertonic saline Hypertonic saline Hypertonic sodium chloride solution. A solution having an osmotic pressure greater than that of physiologic salt solution (0. 9 g NaCl in 100 ml purified water). Hyponatremia
  • Mild symptoms:
    • Fluid restriction
    • Salt tablets
• Adjunctive medications may be used:
  • Furosemide Furosemide A benzoic-sulfonamide-furan. It is a diuretic with fast onset and short duration that is used for edema and chronic renal insufficiency. Loop Diuretics 
  • Vasopressin antagonists (conivaptan, tolvaptan)
  • Demeclocycline Demeclocycline A tetracycline analog having a 7-chloro and a 6-methyl. Because it is excreted more slowly than tetracycline, it maintains effective blood levels for longer periods of time. Tetracyclines 

Differential Diagnosis

The differential diagnosis of SIADH includes other hyponatremic conditions:

• Hyponatremia Hyponatremia Hyponatremia is defined as a decreased serum sodium (sNa+) concentration less than 135 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled via antidiuretic hormone (ADH) release from the hypothalamus and by the thirst mechanism. Hyponatremia: a low sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia concentration in the blood. Generally defined as sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia concentration < 135 mEq/L, with severe hyponatremia Hyponatremia Hyponatremia is defined as a decreased serum sodium (sNa+) concentration less than 135 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled via antidiuretic hormone (ADH) release from the hypothalamus and by the thirst mechanism. Hyponatremia being < 120 mEq/L. The disorders that cause hyponatremia Hyponatremia Hyponatremia is defined as a decreased serum sodium (sNa+) concentration less than 135 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled via antidiuretic hormone (ADH) release from the hypothalamus and by the thirst mechanism. Hyponatremia can be divided into:
  • Disorders that cause impairment in urinary water excretion:
    • Gastrointestinal (GI) losses ( vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia, diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea) 
    • Renal losses (diuretic therapy, adrenal insufficiency Adrenal Insufficiency Conditions in which the production of adrenal corticosteroids falls below the requirement of the body. Adrenal insufficiency can be caused by defects in the adrenal glands, the pituitary gland, or the hypothalamus. Adrenal Insufficiency and Addison Disease)
    • Disorders with edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema (chronic heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR), cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis, nephrotic syndrome Nephrotic syndrome Nephrotic syndrome is characterized by severe proteinuria, hypoalbuminemia, and peripheral edema. In contrast, the nephritic syndromes present with hematuria, variable loss of renal function, and hypertension, although there is sometimes overlap of > 1 glomerular disease in the same individual. Nephrotic Syndrome)
    • Renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome ( acute kidney injury Acute Kidney Injury Acute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury and chronic kidney disease Chronic Kidney Disease Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease)
    • Other causes of excess ADH ( cortisol Cortisol Glucocorticoids deficiency, hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto’s disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism, administration of ADH derivatives)
  • Disorders in which renal handling of water is normal:
    • Primary polydipsia Polydipsia Excessive thirst manifested by excessive fluid intake. It is characteristic of many diseases such as diabetes mellitus; diabetes insipidus; and nephrogenic diabetes insipidus. The condition may be psychogenic in origin. Diabetes Insipidus
    • Cerebral salt wasting
• Cerebral salt wasting: renal loss of Na⁺ with an intracranial disease, which leads to hyponatremia Hyponatremia Hyponatremia is defined as a decreased serum sodium (sNa+) concentration less than 135 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled via antidiuretic hormone (ADH) release from the hypothalamus and by the thirst mechanism. Hyponatremia and a decrease in extracellular fluid Extracellular fluid The fluid of the body that is outside of cells. It is the external environment for the cells. Body Fluid Compartments volume. Presents with volume contraction and SIADH patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship will be euvolemic. The treatment is salt and volume replacement.
• Adrenal insufficiency Adrenal Insufficiency Conditions in which the production of adrenal corticosteroids falls below the requirement of the body. Adrenal insufficiency can be caused by defects in the adrenal glands, the pituitary gland, or the hypothalamus. Adrenal Insufficiency and Addison Disease ( Addison’s disease Addison’s Disease Adrenal insufficiency (AI) is the inadequate production of adrenocortical hormones: glucocorticoids, mineralocorticoids, and adrenal androgens. Primary AI, also called Addison’s disease, is caused by autoimmune disease, infections, and malignancy, among others. Adrenal Insufficiency and Addison Disease): glucocorticoid and mineralocorticoid insufficiency due to the destruction or dysfunction of the entire adrenal cortex Adrenal Cortex The outer layer of the adrenal gland. It is derived from mesoderm and comprised of three zones (outer zona glomerulosa, middle zona fasciculata, and inner zona reticularis) with each producing various steroids preferentially, such as aldosterone; hydrocortisone; dehydroepiandrosterone; and androstenedione. Adrenal cortex function is regulated by pituitary adrenocorticotropin. Adrenal Glands: Anatomy. Cortisol Cortisol Glucocorticoids has a negative feedback Negative feedback Hypothalamic and Pituitary Hormones effect on ADH and adrenocorticotropic hormone Adrenocorticotropic hormone An anterior pituitary hormone that stimulates the adrenal cortex and its production of corticosteroids. Acth is a 39-amino acid polypeptide of which the n-terminal 24-amino acid segment is identical in all species and contains the adrenocorticotropic activity. Upon further tissue-specific processing, acth can yield alpha-msh and corticotropin-like intermediate lobe peptide (clip). Adrenal Hormones (ACTH). The absence of cortisol Cortisol Glucocorticoids thus removes this inhibitory effect, increasing the release of ADH.
• Psychogenic polydipsia Polydipsia Excessive thirst manifested by excessive fluid intake. It is characteristic of many diseases such as diabetes mellitus; diabetes insipidus; and nephrogenic diabetes insipidus. The condition may be psychogenic in origin. Diabetes Insipidus: increase in water intake attributed to a defect in the thirst mechanism, mostly in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with psychosis.
• Hypervolemic hyponatremia Hyponatremia Hyponatremia is defined as a decreased serum sodium (sNa+) concentration less than 135 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled via antidiuretic hormone (ADH) release from the hypothalamus and by the thirst mechanism. Hyponatremia: a deficit of free water excretion that leads to inappropriate water retention in relation to the sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia concentration. This osmotic imbalance results in an expanded extracellular volume and dilutional hyponatremia Hyponatremia Hyponatremia is defined as a decreased serum sodium (sNa+) concentration less than 135 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled via antidiuretic hormone (ADH) release from the hypothalamus and by the thirst mechanism. Hyponatremia. It can be seen in cases of chronic heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR), cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis, and nephrotic syndrome Nephrotic syndrome Nephrotic syndrome is characterized by severe proteinuria, hypoalbuminemia, and peripheral edema. In contrast, the nephritic syndromes present with hematuria, variable loss of renal function, and hypertension, although there is sometimes overlap of > 1 glomerular disease in the same individual. Nephrotic Syndrome. Easy to diagnose based on the significant symptoms and laboratory values of the underlying disease.