Transcript CRP

CRP
C-Reactive Protein
CRP
One of many Acute Phase Proteins
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Produced in response to trauma, tissue damage,
infection and inflammation
Most are made in the liver as a result of increased
synthesis and secretion
The monitoring of an acute phase response can
reflect the extent and activity of an ongoing
problem and can be used to monitor response to
therapy
CRP
CRP
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Five identical polypeptide units
Reference Range <10 mg/L
Half Life 8 hours
Rises within a few hours of insult or injury
CRP
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3 main group of APP
1. Those that show a 50% increase in levels Eg.
Ceruloplasmin
2. Those that show a 2-4 fold increase Eg.
Fibrinogen, haptoglobin a A1T
3. Those that show a several hundred fold increase
Eg. CRP
Activation
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Once CRP has bound to a ligand, C1q
attaches and activates the complement
cascade
CRP is also able to bind FcγRI and FcγRII
These two immunoglobulin receptors create
responses from phagocytic cells
What does CRP bind to?
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CRP has the highest affinity for
phosphocholine on bacteria or as a
mixture of sphingomyelin and
phosphatidylcholine in eukaryotic
membranes.
CRP can also recognize self ligands
such as plasma lipoproteins, damaged
cell membranes, several phospholipids,
small nuclear ribonucleoprotein
components, and apoptotic cells.
Some extrinsic ligands that CRP bind
are glygan, phospholipids, capsular or
cell body components of bacteria,
fungi, and parasites, as well as plant
particles.
CRP
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10 – 40 mg/L suggest mild inflammation or Viral
infection
40 – 200 mg/L acute inflammation or bacterial
infection
>300 mg/L extensive trauma, burns and severe
bacterial infection
CRP
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Why measure CRP ?
– On its own non-specific but very sensitive
– works by binding to exposed DNA in damaged
or dead cells
– scavenger to clear damaged tissue from the
circulation
– needs to be interpreted with full clinical
information to be useful
– Can reflect the extent and activity of an
injury/insult and response to treatment
CRP
Causes of a raised CRP
 Infection
Most microbial infections (serial
measurements are most useful)
 Chronic infection (lower than in acute
infection)
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CRP
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Uncomplicated
virus
infections
(e.g.
Viral
meningitis) will give little or no rise whereas
complex viruses (e.g. Herpes simplex) especially in
immuno compromised patients may lead to major
elevations in serum CRP
CRP changes occur in all ages and in all stages of
health e.g. AIDS, Steroid therapy, irradiation and
may be useful as other clinical signs and symptoms
may be lacking or masked
CRP
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CRP may precede clinical signs of infection by up to
24-48 hours
CRP levels can be used to monitor antibiotic
therapy and further rises can indicate recurrence of
infection
Bacterial meningitis will produce a much higher
level of CRP than viral meningitis
CRP
Causes of a raised CRP
 Inflammatory Disease
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Chronic inflammatory disease associated with
elevated CRP e.g. RA and monitoring serially
reflects the extent and activity of the disease
Persistent elevation of CRP in the absence of
clinical signs and symptoms may indicate
relapse of an underlying inflammation
requiring additional treatment
CRP
Causes of a raised CRP:
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Allograft rejection post transplant
post transplant monitoring can help prompt
possible rejection (must exclude possibility of
infection)
 return to normal followed by a rise can
indicate rejection
 consistent modest elevation may suggest
chronic
rejection
that
may
require
graftectomy
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CRP
Causes of a raised CRP
 Malignancy
Most malignant tumours cause APP response
especially Hodgkins Lymphoma and Renal
Carcinoma
 Some anecdotal evidence suggests CRP levels
correlate to prognosis in prostate and bladder
carcinoma
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CRP
Causes of a raised CRP
 Necrosis
any tissue necrosis causes a rise in CRP
 MI will cause a rise in CRP as will any
embolytic lesion
 Angina does not cause a raised CRP but
pericarditis, PE and pleurisy do.
 CRP cam be used monitor pancreatitis
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CRP
Causes of a raised CR
 Trauma
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CRP rises after any significant trauma,
surgery or burns peaking after 2 days. Any
alteration in this pattern may suggest
underlying infection
CRP
Causes of a raised CRP
 Other
SLE (auto immune disease)
 Leukaemia
 graft v host disease
 Ulcerative colitis
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