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Sepsis and Bilirubin


What is Sepsis:-

Sepsis is a severe medical condition that occurs when the body's response to an infection causes inflammation throughout the body. It can lead to tissue damage, organ failure, and even death if not treated promptly. Symptoms of sepsis includes, sweaty skin, disorientation, shivering, high heart rate, extreme pain, short of breath. Causes of sepsis bacterial infections, viral Infections, fungal Infections, parasitic infections.

How many types of biomarkers affected by sepsis:-

Some of the key biomarkers associated with sepsis include are HR, O2Sat, MAP, DBP, HCO3, BUN, Calcium, Creatinine, Lactate,FiO2, PaCO2, SaO2, AST, Bilirubin Total, Glucose serum, Potassium, Magnesium, Potassium, Troponin I, HGB, PTT, Fibrinogen, Platelets.

Let’s learn about two biomarker here Bilirubin Total and Bilirubin Direct.

Explanation of Bilirubin:-

Bilirubin is a yellowish pigment that is produced during the normal breakdown of red blood cells. It is processed by the liver and excreted in bile. A small amount of bilirubin in your blood is normal. The liver makes bile to help you digest food, and bile contains bilirubin. Most bilirubin comes from the body's normal process of breaking down old red blood cells. A healthy liver can normally get rid of bilirubin. Bilirubin passes through the liver and is eventually excreted out of the body. Bilirubin is a yellowish pigment that is produced during the normal breakdown of red blood cells in the body. It is a byproduct of the heme component of hemoglobin, which is released when old or damaged red blood cells are broken down. 

 What causes high bilirubin levels (hyperbilirubinemia)?

Your body breaks down too many red blood cells too fast. You might be overproducing bilirubin if you have a blood disorder, such as hemolytic anemia, that destroys red blood cells. Your liver might struggle with occasional toxic overload, or it might have a chronic liver disease that affects its functioning. Your biliary system isn’t clearing bile efficiently. There might be a blockage in your bile ducts or your gallbladder that’s causing bile to back up and leak into your bloodstream.

What causes low bilirubin levels (hypo bilirubinemia)?

Sepsis can cause significant fluid shifts within the body, leading to hemodilution, where the concentration of substances in the blood, including bilirubin, becomes diluted. This dilution effect can temporarily lower bilirubin levels. In severe cases of sepsis, the liver's ability to produce bilirubin may be impaired due to decreased hepatic function. This can result from reduced blood flow to the liver, impaired liver metabolism, or other factors related to the systemic inflammatory response.

What are symptoms of abnormal bilirubin ?

Abnormal bilirubin levels can manifest with various symptoms, depending on the underlying cause and severity of the condition. Some common symptoms of abnormal bilirubin levels include:

Jaundice, Dark Urine, Pale stools, Fatigue, and weakness, Abnormal pain or discomfort, Nausea and Vomiting and Itchy skin.

 Organ Failure :

 In severe cases of sepsis, multiple organ failure can occur. The liver is particularly susceptible to damage during sepsis, and impaired liver function can contribute to elevated bilirubin levels. You can have renal failure, respiratory failure, cardiovascular failure, coagulopathy.

Organ Affected:

In Sepsis the organs more frequently affected are kidneys, liver, lungs, heart, central nervous system, and hematologic system.


 Bilirubin Total:-

Normal Range :-

Total bilirubin: 0.1 to 1.2 mg/dL (1.71 to 20.5 µmol/L)

Total bilirubin = direct bilirubin + indirect bilirubin

1.     Unconjugated Bilirubin (Indirect Bilirubin): This form of bilirubin is produced during the breakdown of hemoglobin in red blood cells. It is not water-soluble and needs to be processed by the liver to become water-soluble before it can be excreted in bile.

2.      Conjugated Bilirubin (Direct Bilirubin): After the liver processes unconjugated bilirubin, it 

Becomes conjugated bilirubin, which is water-soluble. This form is excreted in bile and eventually eliminated from the body.

How Bilirubin Total affected by Sepsis:- 

Here are some ways in which sepsis can influence total bilirubin levels:

1.     Hepatic dysfunction: Sepsis can cause dysfunction of the liver, impairing its ability to process bilirubin effectively. The liver may be affected by decreased blood flow, inflammation, or direct damage from the systemic inflammatory response. This can lead to decreased bilirubin clearance and accumulation in the bloodstream, resulting in elevated total bilirubin levels.

2.     Hemolysis: Sepsis can induce hemolysis, the breakdown of red blood cells, either directly or as a consequence of other factors such as disseminated intravascular coagulation (DIC) or the use of certain medications. Increased red blood cell breakdown can result in higher levels of unconjugated bilirubin, contributing to elevated total bilirubin levels.

3.     Impaired bilirubin conjugation: Conjugation of bilirubin in the liver is a crucial step in its metabolism, converting unconjugated bilirubin into a water-soluble form that can be excreted in bile. Hepatic dysfunction associated with sepsis can impair this conjugation process, leading to elevated levels of unconjugated bilirubin and contributing to an increase in total bilirubin levels.

4.     Fluid resuscitation: Aggressive fluid resuscitation, a common strategy in the management of sepsis, can dilute the concentration of substances in the bloodstream, including bilirubin. This dilution effect may lead to lower total bilirubin levels, particularly in the early stages of fluid resuscitation.


Bilirubin Direct:-

 Normal range:

A normal level is: Direct (also called conjugated) bilirubin: less than 0.3 mg/dL (lessthan 5.1 µmol/L) Total bilirubin: 0.1 to 1.2 mg/dL (1.71 to 20.5 µmol/L)

 How Bilirubin Direct affected by Sepsis:-

Here's how sepsis can impact direct bilirubin levels:

  • Hepatic dysfunction: Sepsis can lead to liver dysfunction, impairing the liver's ability to conjugate bilirubin effectively. This dysfunction may result from reduced blood flow to the liver, inflammatory mediators released during the systemic inflammatory response, or direct damage to liver cells. As a consequence, the conjugation of bilirubin may be impaired, leading to decreased clearance of direct bilirubin and elevated levels in the bloodstream.

  • Biliary obstruction: In some cases of sepsis, particularly if it involves infections of the biliary system (such as cholangitis), biliary obstruction can occur. This obstruction can prevent the excretion of conjugated bilirubin into bile, leading to its accumulation in the bloodstream and elevated levels of direct bilirubin.

  • Inflammatory response: The systemic inflammatory response associated with sepsis can directly affect bilirubin metabolism in the liver. Inflammatory cytokines and mediators released during sepsis can disrupt the normal processes of bilirubin conjugation and excretion, contributing to alterations in direct bilirubin levels.

  • Impaired hepatocellular function: Sepsis-induced hepatocellular dysfunction can compromise the ability of liver cells to process and excrete bilirubin effectively.


Monitoring bilirubin levels, along with other markers of liver function and organ dysfunction, is important for assessing the severity of sepsis and guiding appropriate management strategies. Elevated direct bilirubin levels in the context of sepsis may indicate hepatic dysfunction or biliary obstruction, warranting further evaluation and management. Overall, the interpretation of total bilirubin levels in sepsis requires consideration of the underlying pathophysiology, clinical context, and other laboratory findings. Abnormalities in bilirubin levels may require further investigation and medical attention. In sepsis, which is a severe and potentially life-threatening response to infection, bilirubin levels can be affected due to various factors. Sepsis can lead to dysfunction of multiple organs, including the liver, and this can impact the production and clearance of bilirubin.

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