Sepsis is a life-threatening condition that has been around for thousands of years. Sepsis goes by many names including; Septicemia, Sepsis syndrome, Systemic inflammatory response syndrome or SIRS, and Septic shock. Sepsis is one of the leading causes of death in the intensive care unit. Unfortunately, due to its broad symptoms and comorbidity, Sepsis can be difficult to diagnose. Sepsis was first described in 1,000 BC by Ibn Sīnā, an Islamic philosopher, as the putrefaction of blood and tissues with fever. Since then, the disease has been redefined by several notable scholars and scientists. As of the 1990s, sepsis was described as a systemic inflammatory response (SIRS) to a microbial infection. A SIRS is defined as two of the following occurring at the same time:

• Tachypnoea (rapid breathing)
• Tachycardia (rapid heartbeat)
• Pyrexia (fever)
• Hypothermia
• Leukocytosis (high white blood cell count)
• Leukopaenia (low white blood cell count)
• Neutrophilia (high amount of neutrophil granulocytes in the blood)

However, there is some consideration of whether some of these responses should be used in the definition since these symptoms can be a response to an infection. Thus the definition of sepsis has been simplified to a life-threatening organ dysfunction caused by deregulated host response to infection. Sepsis is different from a general infection – the host response is abnormal – as it results in the dysfunction of multiple organs.

What are the risk factors for Sepsis? 
Common risk factors for sepsis include:

Age

• Very young (<2 years of age)
• >55 years of age     

Chronic and serious illness

• Cancer
• Diabetes
• Chronic obstructive pulmonary disease
• Cirrhosis or biliary obstruction
• Cystic fibrosis
• Chronic kidney disease
• Congestive heart failure
• Collagen vascular disease
• Obesity

Impaired immunity

• Transplantation
• Chemotherapy
• Radiation therapy
• Drug-mediated immune suppression
• Blood transfusions     

Breach of natural barriers

• Trauma
• Surgical injury
• Catheterization or intubation
• Burns
• Enterocolitis    

Chronic infections

• HIV
• Urinary tract infections
• Pneumonia
• Decubitus or non-healing dermal wounds

Other

• Protein-calorie malnutrition

Comorbidities and Previous Disorders
Patients with other disorders or comorbidities are more susceptible to sepsis. However, just having these conditions alone are not enough to cause sepsis to develop. In addition to these conditions, the patient would have to experience other risk factors that influence the immune system such as treatment with certain therapies or hospitalization.

Preadmission Status
Related to comorbidity is the health of the patient prior to the development of sepsis. Elderly patients experiencing the following are more susceptible to sepsis.

• Disuse atrophy (Wasting away of the muscles due to lack of use)
• Sarcopenia (Deterioration of skeletal muscle mass, quality, and strength due to aging)
• Altered responsiveness to specific hormones
• Changes in neurological functioning
• Altered cytokine regulation
• Changes in protein metabolism
• Changes in diet

Malnutrition
Malnutrition is particularly a risk factor in the elderly. As one age, their ability to smell fades, resulting in reduced tastes from food and thus a reduced appetite. Other factors also contribute to malnutrition in the elderly population including

• Reduced physical activity
• Fewer resources
• Difficulty moving
• Social isolation
• Insufficient diet
• Chronic illnesses
• Cognitive impairment
• Mood disorders
• Teeth issues
• Overmedication
• Substance abuse

Drugs
The way drugs are absorbed, broken down and affect the body differs from person to person and with age. Thus, drug interactions may have different effects on different people. This is particularly a concern in the elderly since they often take several medications at once.

Intestinal Microbiota
Changes in intestinal microbiota can support pathological processes, like malnutrition and inflammation that promote infection and potentially sepsis.

Immunosenescence
Immunosenescence is the breakdown of the immune system due to age. An impaired immune system has greater difficulty protecting against foreign organisms that could cause infections.  Immunosenescence is characterized by several changes to immune system function including:

• Innate immunity

• Decreased function of macrophages (chemotaxis,
• phagocytosis, apoptosis, TLR expression, and cytokine production)
• Decreased function of neutrophils (such as chemotaxis,
• phagocytosis, signal transduction, and apoptosis)
• Decreased function in dendritic cells (such as antigen presentation,
• chemotaxis, and endocytosis)
• Decreased in phagocytic capacity
• Decreased sensitivity to IFN and growth hormone
• Decreased production of TNF-α and IL-6
• Increased production of IL-10
• Decreased sensitivity to G-CSF
• Decreased expression of TLRs
• Increased number of NK cells
• Decline in NK cell function
• Circulating immature neutrophils

• Changes in T-Cells

• Fewer naïve cells
• Lower naïve CD4 function
• Decrease naïve CD8 function
• Decreased type 1 cytokine response
• Increased type 2 cytokine response
• Decreased function of mitogen-activated protein kinases

• Changes in B-Cell functions

• Decrease in B-cells levels
• Reduced affinity for antibodies
• Decreased response to neoantigens
• Increased level of antibodies
• Hypogammaglobulinemia (a low level of gamma globulins in the blood)

During immunosenescence, levels of IL-6, IL1, and TNF are elevated, causing constant stimulation of the immune system. This inflammation promotes the development and progression of many disease processes. Inflammatory responses also last longer in the elderly than in younger individuals. This may be due to a reduced ability to remove pathogens and/or the inability for counterregulatory mediators to inhibit the pro-inflammatory signal. This prolonged inflammatory response may cause T-cell exhaustion, leading to increased susceptibility to infection. Chronic inflammation also reduces sensitivity to CD4 and CD8 cells, which leads to cell death caused by TNF-α. Macrophage function is also impaired because there is less major histocompatibility complex type II, or MHC II, available resulting in a reduced response to CD4. Once an individual reaches age 60, their thymus, which produces lymphocytes, begins to degrade resulting in a decrease in production of T-, CD4 and CD8 lymphocytes. This reduction leads to a reduced responsiveness to new antigens.