Acute Phase Reactants Infection • Humans are prey to thousands of infectious agents ranging from submicroscopic viruses to several meters long tape worms. • Infections can be caused by different causative agents like – – – – – – Viruses Bacteria Fungi Protozoa helminths and some abnormal forms of host proteins called prions. Host Immune Response to infections Infections and Mortality • Infectious diseases are an important health problem worldwide despite the availability of effective vaccines and antibiotics for many types of infections the estimated 7.7 million deaths were associated with bacterial pathogens constituted 13.6% of all global deaths in 2019. • Other infections like Influenza, pneumonia, Lowerrespiratory infections, HIV/AIDS, and malaria are also leading causes of mortality. Acute Phase Response • Human body has an acute phase response to different conditions like infection, trauma, infarction and other inflammatory diseases. • During this acute phase response serum level of certain proteins in raised by approximately 25 %. These are called acute phase proteins such as CRP and procalcitonin. • Erythrocyte Sedimentation rate is a non-protein or indirect Acute Phase Reactant which indicates certain pathologic conditions including infections. Role of Acute Phase Reactants in Infection • Acute-phase reactants increase or decrease in response to inflammatory stimuli such as infections, trauma, acute arthritis, systemic autoimmune disorders, and neoplasms • The response is proportional to the severity of the inflammatory stimulus and is mediated by pro-inflammatory cytokines such as interleukin (IL)-6, IL1, tumor necrosis factor-alpha, and interferon gamma. Erythrocyte Sedimentation Rate • The ESR measures the rate at which erythrocytes fall or settle in the plasma of a randomly drawn anticoagulated blood specimen over a specified period of time. • ESR is a good indicator of inflammation and infection in body. • There are a lot of other conditions in which ESR is raised. Erythrocyte Sedimentation Rate • Normal Range – Males: 0 to 22 mm/h – Females: 0 to 29 mm/h C Reactive Protein • C-reactive protein is the classic acute phase protein in inflammatory reactions. • Its concentration increases rapidly during inflammatory conditions. • In normal healthy individuals it’s a trace protein and its concentration ranges up to 5 mg/L. • The increase in CRP level begins within 6 to 12 hours and peak value is reached within 24 to 48 hours . Mechanism of Release of CRP Infection • Bacterial or Viral Release of Inflammatory Mediators • IL-1, IL-6, IL-8 and TNF- Liver Release of CRP Five Identical Polypeptide Chains Of CRP C Reactive Protein • Reference Ranges – In healthy individuals: less than 5 mg/L. – Severe infection/Inflammation: More than 100 mg/L. Procalcitonin • Procalcitonin is a precursor protein of the hormone calcitonin produced by parafollicular cells of thyroid and neuroendocrine cells of the lung and the intestine. • It is undetectable in healthy individuals but is produced ubiquitously in response to endotoxin or mediators released following bacterial infections. Procalcitonin Procalcitonin • PCT is among the most promising sepsis markers, capable of complementing clinical signs and routine lab parameters of severe infections. • It is detectable within 2 to 4 hours and peaks within 6 to 24 hours. • PCT production is not impaired by neutropenia or other immunosuppressive states. Procalcitonin • In case of sepsis, early diagnosis and prompt antimicrobial therapy is crucial in the treatment of sepsis for saving lives. • As compared to ESR and CRP, PCT is a better marker of infection or inflammation. • It is specifically associated with bacterial infection thus is a good diagnostic tool in case of sepsis. Reference Ranges • Normal – <0.1 ng/mL • Suspected Sepsis – 0.1 to 0.5 ng/mL- Low likelihood for sepsis. – >0.5 ng/mL- Increased risk of sepsis. – >2.0 ng/mL- High risk of sepsis/ septic shock.
