What causes sepsis?

Summary

Sepsis is a life-threatening condition. Sepsis is caused by:

• A severe infection - usually bacterial, but sometimes fungal or viral.
• Widespread inflammation throughout the body, as the immune system tries to respond to the infection.

Inflammation is usually a good thing for fighting off infection. In sepsis, the immune system gets out of control, and the extensive inflammation causes tissue damage around the body.

This can cause fluid to leak out of blood vessels, causing a drop in blood pressure, which stops organs from getting enough blood flow, leading to organ failure.

In this series of articles centred around sepsis, you can read about symptoms of sepsis, sepsis treatment, and the causes of sepsis - all written by one of our expert GPs.

The rest of this feature will take an in-depth look at the causes of sepsis, as, at Patient, we know our readers sometimes want to have a deep dive into certain topics.

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Sepsis causes

Infection

Infections are the initial cause of sepsis.

Usually, when we get an infection, it stays in one part of the body. The immune system is good at keeping it in one place, and, eventually, getting rid of it completely.

In sepsis, infection spreads and triggers a chain reaction of inflammation throughout the body. The infection can spread because:

• The germs (bacteria/fungi/viruses) are particularly aggressive and able to defeat the immune system.
• The immune system is already weakened and less able to defend against the germs.

Some people might have a combination of both.

Germs in sepsis can spread to the blood, causing septicaemia - blood poisoning. This allows them to get all around the body, causing infection in other organs and triggering the immune system throughout the entire body.

The most common type of infection that causes sepsis is a lung infection (pneumonia). Other common infections that can lead to sepsis are:

• Infection of the intestine or guts - for example, a burst appendix.
• Severe skin infection (cellulitis).
• Urinary tract infection, including kidney infection (pyelonephritis).

Inflammation

The infection causes a major immune response throughout the whole body, triggering the immune system to produce inflammation.

Inflammation is normally a helpful process that helps us fight off infection and heal injuries. But too much inflammation, inflammation in the wrong place, or inflammation at the wrong time, can cause major problems.

In sepsis, out-of-control, widespread inflammation can cause the following:

• Blood vessels to become leaky, causing fluid to leave the blood. This can cause a drop in blood pressure. If blood pressure becomes too low, tissues and organs don't get enough blood and oxygen.
• Damage to the wall of tiny blood vessels. This can cause tissue and organ damage directly.
• Activation of blood clotting - which is also caused by damage to blood vessel walls. Tiny blood clots develop inside small blood vessels, again damaging organs by restricting blood flow. The proteins that cause blood clotting can also get used up by this, meaning that the blood loses its clotting ability, paradoxically leading to bleeding elsewhere. This process is called disseminated intravascular coagulation (DIC).
• This is what happens in meningococcal septicaemia to cause the rash that doesn't disappear with pressure - the glass test. That rash is caused by tiny blood clots in blood vessels under the skin.
• Later on in sepsis, the immune system can become worn out and under-active, leaving the body more vulnerable to infections.

The massive immune response across the body is called a systemic inflammatory response syndrome (SIRS). SIRS can also be caused by things other than infection, like severe burns, pancreatitis, or major bleeding.

Most people define sepsis as SIRS caused by an infection.

Tissue and organ damage

Severe infection and widespread inflammation in sepsis can lead to tissue and organ damage, which in turn can cause organ failure. Organs affected can include:

• The lungs. Sepsis can cause acute respiratory distress syndrome (ARDS), where the lungs fill with fluid due to inflammation. This can make it difficult to breathe and get enough oxygen. People with sepsis may need oxygen via tubing or a mask. If the lungs are severely affected, they may need breathing support with a ventilator in the intensive care unit (ICU).
• The kidneys. Sepsis can cause kidney failure - in this case, something called acute kidney injury (AKI). Intravenous fluids are given to support the kidneys. In severe cases, dialysis might be needed. Some people might be left with chronic kidney disease- CKD.
• The heart and blood vessels. Sepsis can cause blood pressure to drop dangerously low, and the heart and blood vessels may not be able to compensate. Intravenous fluids - fluid through a drip in your veins - can help to increase blood pressure sometimes, but, if these don't work, special medications to help the heart and blood vessels may need to be given in the intensive care unit (ICU).
• The liver. Liver damage can occur due to sepsis.
• The brain. Sepsis can affect the workings of the brain, causing delirium. People with sepsis can become confused, drowsy, agitated, develop slurred speech, and, in severe cases, become unconscious.

How common is sepsis?

Sepsis is relatively common. In the UK, it's estimated that, each year, around 250,000 people develop sepsis, and around 50,000 people die from sepsis.

Sepsis is becoming more common in the UK. This is probably due to a combination of things, such as:

• People being more aware of sepsis, and so recognising and diagnosing it more often.
• More people living with conditions that make them more vulnerable to sepsis.
• More people taking medications that cause a weakened immune system.
• Antibiotic resistance increasing.

Who is more likely to get sepsis?

Sepsis can affect anyone, but some people are at higher risk of getting it. Risk factors for sepsis include:

• Young children, less than 1 year old.
• Older adults, over 75 years of age.
• People with a condition causing a weakened immune system, such as diabetes, HIV/AIDS, or sickle cell disease.
• People taking immune-suppressing medication, including chemotherapy, drugs for rheumatic conditions (for example methotrexate), and biologic medications.
• People who are extremely frail.
• People who have a long-term intravenous line - for example a PICC line - or urinary catheter.
• Women who are pregnant, have just given birth, or recently had a termination of pregnancy.
• People in an ICU who are seriously unwell, and more vulnerable to infections.
• People who misuse alcohol or drugs.

How to avoid infections that cause sepsis

Ways to reduce the risk of getting serious infections include:

• Getting vaccines when recommended. For example, the flu and pneumonia vaccines protect against serious illness.
• Good hygiene. Washing hands regularly - after using the toilet, before preparing food, after blowing your nose, and before caring for others - protects against getting and spreading infections.
• Keeping any wounds clean and well-cared for, to avoid wound infections.
• Treating other long-term conditions - for example, keeping diabetes under good control.