L7 Sepsis, Shock

Sepsis/ Septic Shock
Sepsis
• Sepsis is a condition caused by an overwhelming immune response to an infection in the body. It
is a life-threatening medical emergency.
• When you have an infection, your immune system works to try to fight it. But sometimes your
immune system stops fighting the infection and starts damaging your normal tissues and organs,
leading to widespread inflammation throughout your body.
• At the same time, an abnormal chain reaction in your clotting system can cause blood clots to
form in your blood vessels. This reduces blood flow to the different organs of your body and can
cause significant damage or even failure.
• Infections that lead to sepsis most often start in the lung, urinary tract, skin, or gastrointestinal
tract.
• Without timely treatment, sepsis can rapidly lead to tissue damage, organ failure, and death.
• Sepsis can be induced by several clinical situations: malignant tumours, organ
transplantation, AIDS, radiation therapy, burns, sores, polytrauma, diabetes
mellitus, hepatic failure, renal failure, malnutrition, catheters or different
invasive devices, and urinary catheters.
• Bacterial infections cause most cases of sepsis. Sepsis can also be a result of
other infections, including viral infections, such as COVID-19 or influenza, or
fungal infections.
• The microorganisms involved in the pathogenesis of sepsis are Gram-positive

cocci (Staphylococci, Streptococci) and Gram-negative bacilli (Klebsiella,
Pseudomonas aeruginosa, E. coli), fungi (Candida), parasites, and viruses.
Stages of Sepsis
Sepsis can be classified into three stages:
1. Sepsis
2. Severe sepsis and
3. Septic shock
This scale ranges from infection and bacteremia (bacteria in
bloodstream) to sepsis and septic shock, which can lead to dysfunction
of multiple organs and even death.
Septic Shock
• Septic shock is a severe complication of sepsis that can include
very low blood pressure, an altered mental state, and organ
dysfunction.
• It has a hospital mortality rate of 30–50 percent, making it very
dangerous if not treated quickly.
• Any type of bacteria can cause the infection.
• Fungi such as candida and viruses can also be a cause, although this is
rare.
Sepsis vs. Septic Shock
• https://youtu.be/-MXi4mOMmI4
• Sepsis is infection that becomes widespread by travelling through the

bloodstream.
• Septic shock is sepsis at its most severe, when the blood is no longer
able to get where it needs to go.
• Septic shock is life-threatening.
Survival in Septic Shock
• Recovering from septic shock can take longer than you may expect.
• Survivors may appear to be better, but many live with long-lasting
effects from having been so ill.
• Up to 50% of sepsis survivors live with post-sepsis syndrome (PSS),
which can be mild or severe.
Sepsis Syndrome
• Severe sepsis or Sepsis Syndrome is defined as sepsis associated with multiple organ
dysfunctions.
• Multiple organic dysfunction syndrome (MODS) is defined by the presence of functional

deterioration of at least 2 organs, as an indicator of the impossibility of maintaining
homeostasis.
• Sepsis and the inflammatory response that ensues can lead to multiple organ dysfunction
syndrome and death.
• Its severity is directly proportionate to the intensity of the host body's response.
• In most cases the following organ systems are affected, the cardiovascular system, renal
system, blood, nervous system and liver.
Molecular Mechanism
https://www.youtube.com/watch?v=J-ahUBMkrdM
• Immunodeficiency is common in patients with severe sepsis or septic shock.

• The immune response in sepsis can be characterized by a cytokine-
mediated hyper-inflammatory phase, which most patients survive, and a
subsequent immune-suppressive phase.
• Patients fail to eradicate invading pathogens and are susceptible to
opportunistic organisms in the hypo-inflammatory phase.
• Many mechanisms are responsible for sepsis-induced immuno-suppression,
including apoptotic depletion of immune cells, increased T regulatory and
myeloid-derived suppressor cells, and cellular exhaustion.
• Within the first 24 h of sepsis diagnosis in humans, marked lymphopenia
occurs which is due to recruitment of lymphocytes from the circulation to
sites of inflammation/infection and to apoptotic depletion of CD4 and
CD8 T cells in the blood.
• Postmortem analysis of spleens and lymph nodes from individuals who
succumbed to sepsis confirmed the highly significant loss of CD4 and CD8 T
cells.
• Memory CD8 T cells are highly susceptible to apoptosis in systemic
inflammatory states such as septic shock and are depleted in sepsis.
• These results indicate that depletion of adaptive immune cells is a major
pathologic component of sepsis with potential debilitating effects on host
immunity.
The Role of
Immunoglobulins
IgA, IgG, and IgM are known
to behave synergistically in
sepsis and septic shock, and
the simultaneous occurrence
of low plasma levels of these
antibodies is associated with
reduced survival in patients at
the onset or during sepsis or
septic shock.
Clinical perspectives
• A principal treatment for sepsis is timely, appropriate antibiotic therapy as recommended

by international practice guidelines and multiple professional societies.
• Recent studies show that timely administration of antibiotics in sepsis is associated with
a significant reduction in risk-adjusted in-hospital mortality, particularly for individuals in
shock.
• Yet, antibiotics are unnecessary when no bacterial infection (e.g., viral infection) is
present or when sepsis itself is misdiagnosed.
• In such cases, fast-paced antibiotic administration could result in distracting the clinician
from other acute conditions, expansion of antimicrobial resistance, or even avoidable
adverse drug reactions.
Diagnosis
• A single diagnostic test for sepsis does not yet exist, and so doctors and
healthcare professionals use a combination of tests and immediate and
worrisome clinical signs, which include the following:
• The presence of an infection
• Very low blood pressure and high heart rate
• Increased breathing rate
• Doctors will also do tests to try to confirm the presence—and possibly type—
of infection. A urine sample can provide information about urinary tract
infections (UTI) or kidney problems. Markers found in the blood can show
that the immune system has gone into an over-reactive mode.
Blood tests may reveal the following signs suggestive of sepsis:
• Elevated or low white blood cells – Higher than usual levels of
leukocytes, known as white blood cells (WBCs), are a sign of a current
infection, while too few WBCs indicate that a person is at higher risk
of developing one.
• Lactic acid – When organs and muscles do not receive enough
oxygen, they can release lactic acid. A high level of this in the blood
can indicate that an infection is present.
• Markers of organ dysfunction – Creatinine levels (which test kidney
function), enzymes (to check liver function), and cardiac biomarkers.

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Sepsis/ Septic Shock

• The microorganisms involved in the pathogenesis of sepsis are Gram-positive

• Sepsis is infection that becomes widespread by travelling through the

• Multiple organic dysfunction syndrome (MODS) is defined by the presence of functional

• Immunodeficiency is common in patients with severe sepsis or septic shock.

• A principal treatment for sepsis is timely, appropriate antibiotic therapy as recommended

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