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
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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.