Exploring inflammatory syndrome

1. Erythrocyte sedimentation rate (ESR)

Erythrocyte sedimentation rate (ESR) is a non-specific test for inflammation. It is easy
to perform, widely available and inexpensive making it a widely used screening test. It
is also used as monitoring tool for response to treatment in conditions in which it is
raised.
Erythrocyte sedimentation rate is a non-specific test and is not diagnostic of any
particular disease. It has a high sensitivity but low specificity. Never base a diagnosis
solely on an ESR value, either normal or high. Interpretation of the result should always
be along with the patient's clinical history, examination findings and results of other
tests done.
The ESR test in performed in the laboratory by placing anticoagulated blood in an
upright tube. At the end of an hour of this, the rate of the RBC sedimentation is
measured.

Fig. 1. Performing ESR

Normal values:
ESR values tend to rise with age and are generally higher in women. ESR is also elevated in the
African - American population.
Children
Normal values of ESR have been quoted as 1 to 2 mm/hr at birth, rising to 4 mm/hr 8 days after
delivery, and then to 17 mm/hr by day 14.
Typical normal ranges are:
o Newborn: 0 to 2 mm/hr
o Neonatal to puberty: 3 to 13 mm/hr, but other laboratories place an upper limit of 20.
o Men: 3-9 mm/h
o Women: 6-12 mm/h
o Alert values: > 50 mm/h
Mechanism:
ESR is determined by the interaction between factors that promote (fibrinogen) and resist
(negative charge of RBCs - that repel each other) sedimentation. Normal RBCs settle slowly as
they do not form rouleaux or aggregate together. Instead, they gently repel each other due to the
negative charge on their surfaces.
Increased rouleaux formation contributes to high ESR. Rouleaux are stacks of many RBCs that
become heavier and sediment faster. Plasma proteins, especially fibrinogen, adhere to the red
cell membranes and neutralize the surface negative charges, promoting cell adherence and
rouleaux formation.
The aggregated RBCs in the rouleaux formation have a higher ratio of 'mass to surface area' as
compared to single RBCs and hence sink faster in plasma.
ESR of more than 100 mm/hr is strongly associated with serious underlying disorders like
connective tissue disease, infections and malignancies.

Fig. 2. Rouleaux
2

Any condition that elevates fibrinogen (e.g., pregnancy, diabetes mellitus, end-stage renal
failure, heart disease, collagen vascular diseases, malignancy) may also elevate the ESR.
Anemia and macrocytosis increase the ESR. In anemia, with the hematocrit reduced, the
velocity of the upward flow of plasma is altered so that red blood cell aggregates fall faster. Macrocytic
red cells with a smaller surface-to-volume ratio also settle more rapidly.
Some conditions with very high (>100 mm/hr) ESR:
Malignancies e.g. multiple myeloma
Connective tissue disorders - autoimmune diseases
Tuberculosis
Severe anemia
A decreased ESR is associated with a number of blood diseases in which red blood cells have an
irregular or smaller shape that causes slower settling.
In patients with polycythemia, too many red blood cells decrease the compactness of the rouleau
network and artifactually lower the ESR.
Some conditions with low ESR:
Polycythemia
Severe leukocytosis
Sickle cell disease (anemia)
Hereditary spherocytosis
Hypofibrinogenemia
Corticosteroid use
2. Acute-phase proteins
Acute-phase proteins are a class of proteins whose plasma concentrations increase (positive acutephase proteins) or decrease (negative acute-phase proteins) in response to inflammation. This response
is called the acute-phase reaction (also called acute-phase response).
In response to injury, local inflammatory cells (neutrophil granulocytes and macrophages) secrete a
number of cytokines into the bloodstream, most notable of which are the interleukins IL-1, IL-6 and
IL-8, and TNF-.
The liver responds by producing a large number of acute-phase reactants. At the same time, the
production of a number of other proteins is reduced; these are, therefore, referred to as "negative"
acute-phase reactants.
Positive" acute-phase proteins:
C-reactive protein
Alpha 1-antitrypsin
Alpha 1-antichymotrypsin
Ferritin
Ceruloplasmin
Haptoglobin
Fibrinogen

Negative" acute-phase proteins:

Transferrin
C3 factor of complement (increased consumption)
Transcortin
Albumin
C-reactive protein (CRP)
CRP is a protein found in the blood, the levels of which rise in response to inflammation (an
acute-phase protein). Its physiological role is to bind to phosphocholine expressed on the
surface of dead or dying cells (and some types of bacteria) in order to activate the complement
system.
CRP is synthesized by the liver in response to factors released by fat cells (adipocytes).
CRP is a member of the class of acute-phase reactants, as its levels rise dramatically during
inflammatory processes occurring in the body. This increment is due to a rise in the plasma
concentration of IL-6, which is produced predominantly by macrophages as well as adipocytes.
CRP rises up to 1000 or even more - fold in acute inflammation, such as infection. It rises
above normal limits within 6 hours, and peaks at 48 hours. Its half-life is constant, and
therefore its level is mainly determined by the rate of production.
Normal value: < 2.5 mg/l.
Diagnostic use:
CRP is used mainly as a marker of inflammation, but without prognostic value.
It increases in:
Infections
Myocardial infarction
Cancer
Autoimmune diseases
Metabolic diseases
Apart from liver failure, there are few known factors that interfere with CRP production.
Cardiology diagnostic test
Recent research suggests that patients with elevated basal levels of CRP are at an increased risk
of diabetes, hypertension and cardiovascular disease.
It can be used for monitoring response to therapy (e.g. newborns, infants, and children).
3. Protein electrophoresis
Analytical method for separating particles or combinations of electrically charged particles
under the action of an external electric field.
Acute inflammation type:
Moderate increase of proteinemia
Low serum albumin level

High 1 and 2 globulins

Figure 3. Electrophoresis of serum proteins

Figure 4. Acute inflammation type

4. Fibrinogen serum level
It is a soluble plasma glycoprotein, synthesised by the liver, which is converted by thrombin
into fibrin during blood coagulation.
Fibrinogen levels can be measured in venous blood. Typically fibrinogen is measured in
citrated plasma samples.
Normal levels are about 200-400 mg%.
Diagnostic use:
It may be elevated in any form of inflammation, as it is an acute phase protein. Coagulation
factor, trapping invading microbes in blood clots.

Low levels of fibrinogen can indicate a systemic activation of the clotting system, with
consumption of clotting factors faster than synthesis. This excessive clotting factor
consumption condition is known as disseminated intravascular coagulation.

5. Leukocyte number cell blood count (CBC)

Inflammation often affects the numbers of leukocytes present in the body:
Leukocytosis is often seen during inflammation induced by infection, where it results in a large
increase in the amount of leukocytes in the blood, especially immature cells.
Leukocyte numbers usually increase to between 15 000 and 20 000 cells per microliter, but
extreme cases can see it approach 100 000 cells per microliter.
Bacterial infection usually results in an increase of neutrophils, creating neutrophilia, whereas
diseases such as asthma, hay fever, and parasite infestation result in an increase in eosinophils,
creating eosinophilia.
Leukopenia can be induced by certain infections and diseases, including viral infection,
Rickettsia infection, some protozoa, tuberculosis, and some cancers.

Figure 5. Neutrophilia