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Non-Cardiogenic Causes of Fluid Overload : Uncommon Etiologies and Diagnostic Challenges

Fluid overload, characterized by excessive accumulation of fluid in the body, is commonly associated with cardiac dysfunction. However, there are several non-cardiogenic causes that can lead to fluid overload, posing diagnostic challenges for healthcare professionals. This article explores some of the less common etiologies of fluid overload and discusses the complexities involved in diagnosing these conditions.

Non-Cardiogenic Causes of Fluid Overload: Uncommon Etiologies and Diagnostic Challenges

  1. Renal Causes

    While cardiac dysfunction is a primary contributor to fluid overload, impaired renal function can also play a significant role. Conditions such as acute kidney injury (AKI) or chronic kidney disease (CKD) can lead to fluid retention and subsequent overload. AKI, often caused by infections, medications, or renal ischemia, disrupts the normal filtration and excretion of fluids by the kidneys. Similarly, CKD, a progressive condition, impairs the kidneys’ ability to regulate fluid balance, resulting in fluid accumulation.(1)

  2. Liver Dysfunction

    The liver plays a crucial role in regulating fluid balance through the production of proteins such as albumin, which helps maintain oncotic pressure in the blood vessels. Liver dysfunction, as seen in cirrhosis or acute liver failure, can lead to hypoalbuminemia and a subsequent decrease in oncotic pressure. This disruption impairs fluid distribution, leading to fluid accumulation in the interstitial spaces and, eventually, fluid overload.(2)

  3. Endocrine Disorders

    Certain endocrine disorders can also contribute to fluid overload. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a condition characterized by excessive release of antidiuretic hormone (ADH), leading to water retention and dilutional hyponatremia. ADH acts on the kidneys, promoting water reabsorption and reducing urine output, resulting in fluid overload.(3)

  4. Medications and Iatrogenic Causes

    Some medications can have fluid retention as a side effect, leading to fluid overload. Nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, certain antihypertensives, and hormone replacement therapies are examples of medications that can disrupt fluid balance. Additionally, iatrogenic causes, such as excessive intravenous fluid administration during medical procedures or incorrect fluid replacement strategies, can result in fluid overload.(4)

  5. Miscellaneous Causes

    There are several other less common causes of fluid overload that can pose diagnostic challenges. These include:

    • Lymphatic Disorders: Conditions like lymphedema or obstruction of lymphatic vessels can impair fluid drainage, leading to fluid accumulation in the affected tissues.(5)
    • Hypoalbuminemia: Apart from liver dysfunction, other conditions like protein-losing enteropathy or malnutrition can lead to low levels of albumin, contributing to fluid overload.(6)
    • Systemic Inflammation: Inflammatory conditions such as sepsis or systemic inflammatory response syndrome (SIRS) can disrupt fluid homeostasis, leading to fluid overload.(7)

Other Uncommon Etiologies of Non-cardiogenic Causes of Fluid Overload

In addition to the common etiologies listed above, there are a number of uncommon causes of non-cardiogenic pulmonary edema. These include:

  1. Inhalation Injury: This can occur after exposure to smoke, chemicals, or other irritants.
  2. Acute Kidney Injury: This can lead to fluid overload and increased capillary permeability.
  3. Allergic Reaction: This can cause inflammation and increased capillary permeability.
  4. Drug Overdose: Some drugs, such as opioids and salicylates, can cause non-cardiogenic pulmonary edema.
  5. Medications: Some medications, such as high-dose corticosteroids, can increase the risk of non-cardiogenic pulmonary edema.
  6. Trauma: This can cause inflammation and increased capillary permeability.
  7. Sepsis: This is a life-threatening infection that can cause inflammation and increased capillary permeability.

Diagnostic Challenges of Non-Cardiogenic Causes of Fluid Overload

Diagnosing non-cardiogenic causes of fluid overload can be challenging due to overlapping symptoms and the need for a comprehensive evaluation. Healthcare professionals need to conduct a detailed medical history review, physical examination, and order appropriate diagnostic tests to determine the underlying cause. These tests may include blood tests, urinalysis, imaging studies (such as ultrasound or CT scan), and in some cases, invasive procedures like liver biopsy or renal function assessment.

Other tests that may be helpful in diagnosing non-cardiogenic pulmonary edema include:

  • Arterial blood gas analysis
  • Echocardiogram
  • Pulmonary function tests
  • Lactic acid level
  • Brain natriuretic peptide (BNP) level

Additionally, healthcare providers must be vigilant in recognizing potential non-cardiogenic causes when evaluating patients with fluid overload. A multidisciplinary approach involving nephrologists, hepatologists, endocrinologists, and other specialists may be necessary to arrive at an accurate diagnosis.

While fluid overload is often associated with cardiac dysfunction, it is essential to consider non-cardiogenic causes as well. Renal causes, liver dysfunction, endocrine disorders, medications, and miscellaneous causes can all contribute to fluid overload. Recognizing these uncommon etiologies is crucial for accurate diagnosis and effective management of patients presenting with fluid overload symptoms.

Treatment of Non-Cardiogenic Causes of Fluid Overload

Managing non-cardiogenic causes of fluid overload involves addressing the underlying condition and correcting the fluid imbalance. Treatment strategies may include:

  1. Renal Causes: In cases of acute kidney injury, identifying and treating the underlying cause, along with supportive measures such as fluid restriction, diuretics, or renal replacement therapy, may be necessary. In chronic kidney disease, a combination of dietary modifications, medications to control blood pressure and preserve renal function, and dialysis or kidney transplantation in advanced stages can help manage fluid overload.
  2. Liver Dysfunction: Managing fluid overload in patients with liver dysfunction involves addressing the underlying liver disease. This may include lifestyle modifications, medication adjustments, and in severe cases, liver transplantation. Diuretics may also be prescribed to promote diuresis and alleviate fluid retention.
  3. Endocrine Disorders: Treating underlying endocrine disorders contributing to fluid overload, such as SIADH, often involves restricting fluid intake, administering medications to normalize ADH levels, or addressing the primary cause of hormone dysregulation.
  4. Medications and Iatrogenic Causes: In cases where medications are the cause of fluid overload, healthcare professionals should consider alternative medications with less fluid retention potential or adjust dosage as appropriate. Addressing iatrogenic causes requires reevaluating fluid management strategies and ensuring proper fluid balance during medical procedures.
  5. Miscellaneous Causes: Managing fluid overload related to lymphatic disorders may involve physical therapies, compression garments, or surgical interventions to improve lymphatic drainage. Addressing hypoalbuminemia requires identifying and treating the underlying condition causing low albumin levels. Systemic inflammation-associated fluid overload may require targeted treatment for the underlying inflammatory condition.

Prognosis of Non-Cardiogenic Causes of Fluid Overload

The prognosis for non-cardiogenic pulmonary edema varies depending on the underlying cause. In general, the prognosis is better for people with acute onset of symptoms and no underlying lung disease.


Fluid overload can result from various non-cardiogenic causes, and recognizing these uncommon etiologies is essential for accurate diagnosis and management. Renal dysfunction, liver impairment, endocrine disorders, certain medications, and other miscellaneous causes can all contribute to fluid accumulation in the body.

Diagnosing non-cardiogenic causes of fluid overload can be challenging due to overlapping symptoms and the need for a comprehensive evaluation. A multidisciplinary approach involving various specialists is often necessary to arrive at an accurate diagnosis and implement appropriate treatment strategies.

By understanding and addressing these less common etiologies, healthcare professionals can improve patient outcomes, enhance fluid management strategies, and provide targeted interventions to alleviate fluid overload in diverse clinical scenarios.


  1. KDIGO Clinical Practice Guideline for Acute Kidney Injury: Section 2.1 – Definition and classification of AKI: Link: https://kdigo.org/wp-content/uploads/2016/10/KDIGO-2012-AKI-Guideline-English.pdf
  2. Arroyo V, Moreau R, Kamath PS, et al. Acute-on-chronic liver failure in cirrhosis. Nat Rev Dis Primers. 2016;2:16041. DOI: 10.1038/nrdp.2016.41
  3. Ellison DH, Berl T. The Syndrome of Inappropriate Antidiuresis. N Engl J Med. 2007;356(20):2064-2072. DOI: 10.1056/NEJMra066837
  4. Aronson JK. Side Effects of Drugs: Side Effects of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs). Encyclopedia of Psychopharmacology. Berlin, Heidelberg: Springer; 2010:1- DOI: 10.1007/978-3-540-68706-1_724 
  5. Rockson SG. Lymphedema. Am J Med. 2001;110(4):288-295. DOI: 10.1016/S0002-9343(00)00702-8
  6. Stein J, Dignass AU. Management of Iron Deficiency Anemia in Inflammatory Bowel Disease—A Practical Approach. Ann Gastroenterol. 2013;26(2):104-113. DOI: 10.1016/j.anngastro.2013.04.002
  7. Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med. 2013;369(9):840-851. DOI: 10.1056/NEJMra1208623

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Team PainAssist
Team PainAssist
Written, Edited or Reviewed By: Team PainAssist, Pain Assist Inc. This article does not provide medical advice. See disclaimer
Last Modified On:June 7, 2023

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