Sepsis – Pathophysiology, Treatment, and Prevention.

What is sepsis?

Sepsis is a life-threatening illness caused by your body’s response to an infection. Your immune system protects you from many illnesses and infections, but it’s also possible for it to go into overdrive in response to an infection.

Sepsis develops when the chemicals the immune system releases into the bloodstream to fight an infection cause inflammation throughout the entire body instead. Severe cases of sepsis can lead to septic shock, which is a medical emergency.

What are the stages of sepsis?

Some medical researchers consider sepsis to have three stages.

  • The first stage is the least severe and usually has symptoms of fever and an increased heart rate.
  • The second stage is more severe and is characterized by symptoms of difficulty breathing and possible organ malfunctions.
  • The third stage is the most severe stage (septic shock or severe sepsis) with life-threatening low blood pressure.

Not all researchers agree with these stages; some researchers choose not to consider sepsis in stages.

Pathophysiology of sepsis

The pathogenesis of sepsis is not completely understood. An inflammatory stimulus (eg, a bacterial toxin) triggers the production of proinflammatory mediators, including TNF and IL-1. These cytokines cause neutrophil–endothelial cell adhesion, activate the clotting mechanism and generate microthrombi. They also release numerous other mediators, including leukotrienes, lipoxygenase, histamine, bradykinin, serotonin, and IL-2. They are opposed by anti-inflammatory mediators, such as IL-4 and IL-10, resulting in a negative feedback mechanism.

Initially, arteries and arterioles dilate, decreasing peripheral arterial resistance; cardiac output typically increases. This stage has been referred to as warm shock. Later, cardiac output may decrease, BP falls (with or without an increase in peripheral resistance), and typical features of shock appear.

Even in the stage of increased cardiac output, vasoactive mediators cause blood flow to bypass capillary exchange vessels (a distributive defect). Poor capillary flow from this shunting along with capillary obstruction by microthrombi decreases delivery of oxygen and impairs removal of carbon dioxide and waste products. Decreased perfusion causes dysfunction and sometimes failure of one or more organs, including the kidneys, lungs, liver, brain, and heart.

Coagulopathy may develop because of intravascular coagulation with consumption of major clotting factors, excessive fibrinolysis in reaction thereto, and more often a combination of both.

Sepsis Causes and Risk Factors

Bacterial infections are most often to blame. But sepsis can also result from other infections. It can begin anywhere bacteria or viruses enter the body. So, it could sometimes be caused by something as minor as a scraped knee or nicked cuticle. If you have a more serious medical problem such as appendicitis, pneumonia, meningitis, or a urinary tract infection, you’re also at risk.

If you have an infection of the bone, called osteomyelitis, it could lead to sepsis. In people who are hospitalized, the bacteria that trigger sepsis can enter the body through IV lines, surgical incisions, urinary catheters, and bedsores.

Anyone can get it, but certain groups of people are at greater risk. They include:

  • People whose immune systems are not working well due to illnesses like HIV/AIDS or cancer
  • People who take drugs that suppress the immune system, like steroids and those used to prevent rejection of transplanted organs
  • Very young babies
  • The elderly, especially those with other health problems
  • People who have recently been hospitalized and/or had major surgeries
  • People with diabetes

Signs and Symptoms of sepsis

The most important step for patients or people around them suspecting sepsis is that they:

  • Do not attempt to make a home diagnosis
  • Instead, get medical help as soon as possible – the symptoms of sepsis from a bad infection are serious
  • The symptoms can signal other conditions that would also need medical help

The signs and symptoms of sepsis following a bad infection are often subtle and can be mistaken for those of other serious conditions. However, sepsis typically involves the following main features in someone who has had a recent infection, and symptoms can come on quickly.

Get urgent medical help – go to the emergency department whenever sepsis is suspected. It often produces:

  • Fever (high temperature, pyrexia), and there may be chills and shivering
  • Fast heart rate/pulse (tachycardia)
  • The rapid rate of breathing (tachypnea)
  • Unusual levels of sweating (diaphoresis)

It is particularly important to call for urgent medical help if sepsis has reached a late stage – severe sepsis or septic shock.

Call an ambulance whenever sepsis is suspected and there is:

  • Dizziness or feelings of faintness
  • Confusion or a drop in alertness, or any other unusual change in mental state, including a feeling of doom or a real fear of death
  • Slurred speech
  • Diarrhea, nausea, or vomiting
  • Severe muscle pain and extreme general discomfort
  • Difficulty breathing – shortness of breath
  • Low urine output (not needing to urinate for a whole day, for example)
  • Skin that is cold, clammy, and pale, or discolored or mottled
  • Skin that is cool and pale at the extremities, signaling poor blood supply (poor perfusion)
  • Loss of consciousness

Get medical help for anyone whether the skin feels unusually warm or cold; either can happen with sepsis. The elderly and very young are particularly vulnerable to sepsis after infection and also more vulnerable to the worsening of any sepsis condition.

When calling for medical help, going to the emergency department, or speaking to doctors and nurses, it is important to mention any recent infection, surgical procedure, or if the patient has a compromised immune.

Such a medical history is more likely to mean there has been an infection, this alerts the doctors to the possibility of sepsis if they see the typical features.

Long-term complications of sepsis

  • Sepsis is a severe complication of the infection. Further complications depend on the extent of any organ damage. This will depend on the overall health of the individual, and how quickly they get treatment.
  • Many people who recover from severe sepsis recover without long-term problems, but some people may have lifelong organ damage.
  • This is more likely for those with a long-standing condition, such as kidney disease. Damage to the kidneys may be so severe that dialysis is needed.
  • In some cases, the person’s immune system is affected. This may increase their likelihood of having future infections.

What Tests Do Health Care Professionals Use to Assess and Diagnose Sepsis?

In the hospital, the doctor may conduct various tests. These tests will either be geared toward the patient’s specific symptoms (for example, a chest X-ray if the patient is suspected of having pneumonia) or many different tests if the source of the sepsis is not known.

  • Blood work may be done by inserting a needle into a vein in the patient’s hand or arm and drawing blood into several tubes. This blood may be analyzed to see if the patient has an elevation in the white blood cell counts.
  • Blood may also be sent to the lab to be placed on a medium where bacteria will grow if they are present in the blood. This is called a blood culture. Results from this test usually take over 24 hours (the time required to look for bacterial growth). Lab technicians may also look for bacteria in the blood under the microscope on slides.

Samples may be taken of sputum (mucus), urine, spinal fluid, or abscess contents to look for the presence of infectious organisms.

  • To obtain urine that is not contaminated and to measure the amount of urine being produced, a flexible rubber tube may be placed into the bladder (catheter).
  • Spinal fluid may be obtained from the lower back (spinal tap or lumbar puncture) to evaluate if there is an infection in the brain or fluid surrounding the brain and spinal cord. After the skin is cleaned and numbed, a hollow needle is placed between the bones of the spine into the canal containing the spinal cord. Because the needle is placed lower than the location where the cord ends, there is little danger of injuring the nerves of the spinal cord. When the needle is in the correct spot, the doctor will let the fluid drip into tubes. The sample of fluid is sent to the lab for testing.

Other tests may include a chest X-ray to look for pneumonia or a CT scan to see if there is an infection in the abdomen.

  • A dye (contrast) might be injected into a vein during a CT scan to help highlight certain organs in the abdomen.
  • Ultrasound might be used to look at your gallbladder and ovaries.
  • Magnetic resonance imaging (MRI) can also be a useful test to look at certain areas of the body.
  • Usually, a radiologist reads the results and notifies the patient’s doctor.

In the hospital, the patient may be placed on a cardiac monitor, which will show the patient’s heart rate and rhythm.

Similarly, the patient is usually placed on a pulse oximeter which indicates the amount of oxygen in the blood.

If the patient is a young child who is ill and being evaluated for sepsis, he or she will get similar tests and treatment.

Treatment of sepsis

Early, aggressive treatment boosts your chances of surviving sepsis. People who have sepsis require close monitoring and treatment in a hospital intensive care unit. If you have sepsis or septic shock, lifesaving measures may be needed to stabilize breathing and heart function.


A number of medications are used in treating sepsis and septic shock. They include:

  • Treatment with antibiotics should begin immediately. Initially you’ll receive broad-spectrum antibiotics, which are effective against a variety of bacteria. The antibiotics are administered intravenously (IV).
  • After learning the results of blood tests, your doctor may switch to a different antibiotic that’s targeted to fight the particular bacteria causing the infection.
  • Intravenous fluids. People who have sepsis often receive intravenous fluids right away, usually within three hours.
  • If your blood pressure remains too low even after receiving intravenous fluids, you may be given a vasopressor medication, which constricts blood vessels and helps to increase blood pressure.

Other medications you may receive include low doses of corticosteroids, insulin to help maintain stable blood sugar levels, drugs that modify the immune system responses, and painkillers or sedatives.

Supportive care

People who have sepsis often receive supportive care that includes oxygen. Depending on your condition, you may need to have a machine help you breathe. If your kidneys have been affected, you may need to have dialysis.


Surgery may be needed to remove sources of infection, such as collections of pus (abscesses), infected tissues or gangrene.


It can take some time to recover from sepsis, and some people will not fully recover their previous health. The recovery process will start in the hospital and continue at home.

Patients are advised to take things slowly and get plenty of rest.

They will continue to experience:

  • Weakness and tiredness
  • Breathlessness
  • General body pain
  • Difficulty moving
  • Difficulty sleeping
  • Loss of appetite and weight
  • Brittle nails, hair loss, and dry, itchy skin

The person may also feel confused, anxious, and depressed. They may be irritable and frustrated, and they may have flashbacks.

Eating a balanced diet, exercising where possible, talking to friends and family, and resting can all help with the recovery process.

How to Help Prevent Sepsis?

  • Get vaccinated against flu, pneumonia, and any other potential infections
  • Prevent infections that can lead to sepsis by: Cleaning scrapes and wounds and practicing good hygiene by washing hands and bathing regularly

If you have an infection, look for signs like:

  • Fever and chills
  • Extreme weakness, dizziness, lethargy or confusion
  • Signs of compromised organ function: difficulty breathing, rapid heart rate, low blood pressure, low urine output
  • Rash
  • Excessive thirst
  • Loss of appetite
  • Skin or wounds that become red, hot, tender and swollen or draining pus

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  1. what are the best vasopreesors used in such cases?

    • Norepinephrine (Levophed) should be provided as the first-line vasopressor (Grade 1B).
      Epinephrine is considered the next-line agent for septic shock after norepinephrine in the Surviving Sepsis Guidelines.

  2. which are the most infectious Organism to Spread Sepsis prolong?

  3. what is the cause of septicemia and what cure is there

    • Septicemia is caused by an infection in another part of your body. This infection is typically severe. Many types of bacteria can lead to septicemia. The exact source of the infection often can’t be determined. Antibiotics are used to treat the bacterial infection that’s causing septicemia. There isn’t typically enough time to figure out the type of bacteria. Initial treatment will usually use “broad-spectrum” antibiotics.

  4. I want real drugs to all the diseases not just biotics and antibiotics

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