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Course Instructions
Please proceed through the course by clicking on the blue arrows or text links. Use the table of contents to monitor your progress. Your progress will be saved automatically as you proceed through the course, and you may later continue where you left off even if you use a different computer. You may encounter practice questions within the course, which are not graded or recorded.
Course Info
This course carries the following continuing education credits:
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P.A.C.E. Contact Hours: 1.00 hour(s) Course Number: 578-041-12 Florida Board of Clinical Laboratory Science CE - General (Clinical Chemistry/UA/Toxicology): 1.00 hour(s)
Sepsis Definition
Sepsis is an overreaction by the immune system to infection (usually bacterial, but could be viral, fungal, or parasitic). It is a systemic inflammatory response, which can be life-threatening. A weakened immune system, certain chronic disorders, an artificial joint or heart valve, and certain heart valve abnormalities increase the risk for sepsis. Sepsis has been reported to be the most common cause of death in the noncoronary intensive care unit. Note that it is sepsis (the immune system's response) that is usually the cause of death and not the infection. Therefore, it is crucial that the recognition of sepsis be made as quickly as possible. Delay in identifying sepsis limits the effectiveness of treatment. Sepsis includes two or more of the following symptoms:
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A body temperature >38C (100.4F) or <36C (96.8 F) A heart rate >90 beats/minute Respiratory rate >20 breaths/minute An alteration in the white blood cell (WBC) picture, such as a count >12.0 x 10 /L or <4.0 x 10 /L or >10% immature neutrophils
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However, these inflammatory responses may also occur in the absence of infection, a condition termed systemic inflammatory response syndrome (SIRS). When the cause of the systemic inflammatory response is infection, the condition is defined as sepsis.
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Hyperglycemia in the absence of diabetes Elevated C-reactive protein (CRP) Elevated procalcitonin Elevated lactic acid (lactate)
Severe Sepsis
If sepsis progresses to severe sepsis, organs begin to shut down. Multiple organ (lung, liver, and kidney) dysfunction is possible, which may result in death. Severe sepsis is characterized by organ dysfunction, hypoperfusion, and/or hypotension.
Septic Shock
A patient progresses to septic shock from severe sepsis if the hypotension due to the systemic infection does not respond to fluid resuscitation. Septic shock is life-threatening with a mortality rate of 40 - 60%.
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Continuous cycle of inflammation and coagulation Weakening of the heart caused by the strain of increased pumping in an attempt to compensate for the decreased blood flow Cardiovascular insufficiency Tissue hypoxia Multiple organ failure
Feedback Sepsis results in an immune response by the body. This response includes increasing body temperature and leukocytes in order to help fight off the infection, and increased heart rate in order to get more blood and oxygen to the tissues. Erythrocytosis is not part of the immune response.
Biomarkers
An ideal biomarker for diagnosis of disease has these properties:
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High sensitivity (accurately identifies the presence of disease and has few false-negatives) High specificity (accurately detects the absence of disease and has few false-positives) Relates to the extent of disease Changes as the clinical condition evolves
A biomarker that is able to identify sepsis, or determine which patients with sepsis are likely to develop severe sepsis, would be very useful. However, an ideal marker for sepsis is still not available. C-reactive protein (CRP), procalcitonin (PCT), and lactic acid (lactate) are currently the tests that are most often used to aid in the detection of sepsis. However, test specificities and sensitivities are not high and if these tests are used to presumptively diagnose sepsis prior to availability of the blood culture or other culture reports, the results must be interpreted along with the clinical assessment. As mentioned earlier in the course, sepsis may include these symptoms:
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A body temperature >38C or <36C A heart rate >90 beats/minute Respiratory rate >20 breaths/minute An alteration in the white blood cell (WBC) picture, such as a count >12.0 x 109 /L or < 4.0 x 109 /L or >10% immature neutrophils Altered mental status
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Edema Hyperglycemia in the absence of diabetes Elevated CRP Elevated PCT Elevated lactic acid (septic shock)
Glucose
Hyperglycemia commonly develops in sepsis; it is a part of the body s inflammatory response as well as a common response to stress. However, hyperglycemia does not always develop with sepsis, and in some patients, it may develop even in mild disease. Therefore, it cannot be considered a reliable biomarker as it lacks both specificity and sensitivity. It may be used along with other indicators to identify sepsis.
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Rheumatic diseases Systemic lupus erythematosus Systemic sclerosis Sjogren syndrome Inflammatory bowel disease Leukemia Transfusion associated graft-vs-host disease
Once the determination has been made that sepsis is present and therapy has been initiated, CRP is useful for monitoring response to antibiotics and predicting prognosis.
Procalcitonin (PCT)
PCT increases early in infection and has a greater specificity for infection than CRP. Increased PCT can be observed within 3-6 hours of infection. PCT enables the differentiation between a severe bacterial infection and other clinical conditions that may be causing a systemic inflammatory response, allowing antibiotic treatment to begin sooner. Elevated PCT values generally correlate well
with positive blood and other culture results. Depending on the clinical assessment, a PCT concentration >0.1 ng/mL (reference value <0.05 ng/mL) can indicate clinically relevant bacterial infection. PCT levels are usually low in viral disorders, chronic inflammatory conditions, or autoimmune conditions.
Feedback A biomarker with high sensitivity accurately identifies the presence of disease and has few false-negatives. A biomarker with high specificity accurately detects the absence of disease and has few false-positives.
Feedback CRP is a sensitive marker for detection and monitoring progression of inflammation and tissue damage. However, CRP lacks specificity. Once a diagnosis of sepsis has been made and therapy has been initiated, CRP is useful for monitoring response to antibiotics and predicting prognosis.
Feedback PCT usually rises within 3-6 hours of infection. CRP also increases rapidly following infection, but is not as specific for infection as PCT. A rise in CRP could also occur with SIRS. Lactic acid is usually used to detect and monitor impaired circulation and tissue oxygenation in critically ill patients. .
Feedback The statement is false. Lactic acid will increase. When cells do not receive enough oxygen because they are not receiving enough blood, they release excess lactic acid into the bloodstream. Organ failure as a result of septic shock may be indicated by unexplained metabolic acidosis (low blood pH and low bicarbonate level) and extremely elevated lactic acid, where blood pH is <7.30 and plasma lactic acid is >1.5 times the upper limit of the laboratory s established reference values.
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Synthesis of PCT is regulated by the Calc-1 gene located on chromosome 11. In healthy individuals, production of PCT, and subsequently calcitonin, is restricted to the thyroid C cells.
the presence of oxygen, pyruvate is converted to acetyl-coenzyme A (CoA), which ultimately produces energy in the form of ATP. However, in an oxygen-deficient environment, CoA is not produced and pyruvate is converted to lactate through anaerobic metabolism. The quantitative measurement of lactic acid in plasma indicates the severity of oxygen deprivation. An elevated lactate is known to be associated with increased mortality rates. If the lactate can be cleared, prognosis improves. Patients who develop severe sepsis or septic shock commonly demonstrate hyperlactemia and lactic acidosis. Increased lactate production during anaerobic metabolism and decreased lactate clearance are likely contributors to hyperlactemia.
Feedback In healthy individuals, procalcitonin is only synthesized by the thyroid C cells. In bacterial infections, PCT is synthesized in various extrathyroidal neuroendocrine tissues.
Future Perspectives
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Immunosuppresive conditions, including HIV/AIDS, cancer, and solid organ tumors Increased use of invasive procedures Immunosuppressive drugs Chemotherapy Organ transplantation Prosthetic implants Antimicrobial resistance
Age is a risk factor in itself, even without an underlying medical condition. With the aging of the "baby boomer" generation, the United States will soon have a larger group of people over the age of 65 than it has every had before in the history of the country. The number of people over the age of 65 in 2030 is predicted to be double what it was in 2000. Oltermann has dubbed this potential occurrence the "sepsis boom."*
*Reference: Oltermann MH. The coming "sepsis boom...". MLO online. Available at: http://www.mlo-online.com/articles/201202/thecoming-and-ldquosepsis-boom-and-rdquo.php. Accessed October 30, 2012.
Future Perspectives
References
References
Angus DC, Linde-Zwirble WT, Lidicker J, et al. Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29:1303-1310. Castelli GP, Pognani C, Meisner M, et al. Procalcitonin and C-reactive protein during systemic inflammatory response syndrome, sepsis, and organ dysfunction. Available at: http://ccforum.com/content/8/4/R234. Accessed October 30, 2012. Faix J. Sepsis: New approaches to diagnosis and treatment. Clin Lab News. July 2012;38(7):12-14. Harbarth S, Holeckova K, Froidevaux C, et al. Geneva Sepsis Network. Diagnostic value of procalcitonin, interleukin-6, and interleukin-8 in critically ill patients admitted with suspected sepsis. Am J Respir Crit Care Med. 2001;164:396-402. LaRosa SP. Sepsis. Cleveland Clinic website. Available at: http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/infectious-disease/sepsis/#s0050. Accessed October 30, 2012. Mller B, Becker KL, Schchinger H, et al. Calcitonin precursors are reliable markers of sepsis in a medical intensive care unit. Crit Care Med. 2000;28(4):977-983. . Oltermann MH. The coming "sepsis boom...". MLO online. Available at: http://www.mlo-online.com/articles/201202/the-comingand-ldquosepsis-boom-and-rdquo.php. Accessed October 30, 2012.