Sepsis is a life-threatening disease of disproportionate inflammatory response to microbial infection. The elderly and infants are more prone to sepsis due to a weakened immune system. People suffering from chronic health disorders associated with the kidney, liver, and other organs have a high risk of sepsis. Immune suppression  is also a major predisposing circumstance for sepsis.

Sepsis, bacteria in blood. 3D illustration showing rod-shaped bacteria in blood with red blood cells and leukocytes. Image Credit: Kateryna Kon / Shutterstock

Impaired Immune Response

Generally, immune cells defend against foreign pathogens that invade the body. During sepsis, the immune system malfunctions in one of the following ways:

• Overreaction: the invading organism triggers a devastating immune response.
• Underreaction: the immune system does not work effectively or does not work at all. The actual reasons for an impaired immune system is not known, but  some circumstances like immune suppression and immunodeficiency disorder caused by trauma, splenectomy, AIDS, etc., decrease the efficiency.

Direct Cause

1. Microbial infection

Microbes enter into the human body through openings like the airway, mouth, or urinary tract, and by lesions, bug bites, and surgical wounds on the skin. The most common regions where the multiplication of microbes leads to sepsis are in the blood, bowel, lungs, kidney, and pelvis.

Bacteria

Bacterial infections are the main causes of sepsis. Studies have revealed that Gram-negative bacteria more commonly cause sepsis than Gram-positive bacteria. Bacterial triggers are responsible for the secretion of proinflammatory cytokine.

• Gram-negative bacteria: Escherichia coli, Klebseilla pneumoniae, Enterobacter, Pseudomonas aerugi nosa, and Proteus are examples of Gram-negative bacteria that can cause sepsis. Endotoxin, otherwise called lipopolysaccaride, is the trigger element formed by this kind of bacteria.
• Gram-positive bacteria: Examples of Gram-positive bacteria causing sepsis are Staphylococcous aureus, Streptococcus pyrogens, S. pneumoniae, and Enterococcus. The trigger constituents of this group of bacteria are superantigens, peptidoglycan, lipoteichoic acid, and hemolysins. Among these, superantigens are more potent, since they bind to the receptor located on the outer surface of T-cell, thereby making the cells react against the body.

Virus

Viruses such as influenza, HIV, and chicken pox and conditions like viral pneumonia and viral meningitis can cause sepsis. The pathogenesis of viral sepsis is associated with the degeneration and cellular necrosis of infected cells leading to a systemic inflammatory reaction.

Fungi

Most commonly, fungal infections develop on skin, but the risk of sepsis increases when it enters a body with impaired immunity. Candida, Pneumocystis jirovercii, Histoplasma, and Aspergillus are fungi that can cause serious infections. Among them, invasive candidiasis can lead to sepsis.

Pathogenesis

1. Microbes stimulate cytokine signaling, which in turn triggers the hyperbolic inflammatory reaction.
2. The white blood cell (WBC) count increases, disseminating inflammation throughout the body called a systemic inflammatory response syndrome (SIRS).
3. The persistent activation of WBC leads to tissue necrosis (death) of an organ.
4. Since the coagulation system is closely connected to inflammation, clots are formed throughout the body, rupturing blood vessels, which can result in fluid leakage from circulation.
5. Insufficient perfusion of blood in organs leads to hypoxia (oxygen deficiency), triggering nitric oxide (NO) synthesis.
6. Stimulation of tumor necrosis component and increased levels of NO result in systemic hypotension.

2. Immune suppression

1. Chemotherapy: Chemotherapy kills cancer cells, but along with that healthy cells like white blood cells, which helps to fight infection, are  also killed. So, chemotherapy patients are more susceptible to infections.
2. Organ transplantation: Anti-rejection drugs are given to prevent rejection of transplanted organs. However, these drugs decrease the ability of the defense mechanism of the body to fight even against very common infections like flu and colds.
3. Medications: Drugs prescribed to treat some autoimmune disorders like rheumatoid arthritis and psoriasis can make a person more prone to infections.  For example, corticosteroids and TNF inhibitors suppress immunity.
4. Splenectomy: The spleen is an organ that consists of WBC, platelets, and other immune system elements. Damage or the removal of spleen directly affects the immunity of a person, resulting in immune suppression.

Indirect Causes

Chronic illness: Infections of the vital organs like pneumonia or a urinary track infections, can lead to sepsis as the organism enters the circulation. A person with chronic illness has a higher risk of developing sepsis.

Contaminated instruments: Some contaminated medical instruments can lead to infections. For example, vascular catheter insertion may bring about bacteria in blood .

Serious burns and wounds: Sometimes, burns and wounds get contaminated by microbes. If not treated, this can cause serious infection resulting in sepsis.