62
U N I T 1
Cell and Tissue Function
infections, and brucellosis. These types of agents have
one thing in common: they are poorly degraded and
usually are not easily controlled by other inflammatory
mechanisms. The epithelioid cells in granulomatous
inflammation may clump in a mass or coalesce, forming
a multinucleated giant cell (often referred to as a foreign
body giant cell) that attempts to surround the foreign
agent (Fig. 3-6). A dense membrane of connective tissue
eventually encapsulates the lesion and isolates it.
FIGURE 3-6.
Foreign body giant cell.The numerous nuclei are
randomly arranged in the cytoplasm. (From Rubin E, Farber LL.
Rubin’s Pathology: Clinicopathologic Foundations of Medicine.
3rd ed. Philadelphia, PA: Lippincott Williams &Wilkins;
1999:40.)
SUMMARY CONCEPTS
■■
Chronic inflammation involves infiltration with
macrophages, lymphocytes, and fibroblasts,
leading to persistent inflammation, fibroblast
proliferation, and scar formation.
■■
Among the conditions associated with chronic
inflammation and inappropriate activation of
the immune system are low-grade inflammation
associated with atherosclerosis and type 2 diabetes
mellitus; autoimmune disorders; and susceptibility
to cancer due to deoxyribonucleic acid damage,
increased tissue proliferation, and creation of an
environment rich in cytokines and growth factors
that favor tumor cell development and growth.
■■
A granulomatous lesion is a distinctive form
of chronic inflammation characterized by
aggregates of epithelioid macrophages that
“wall off” the causal agent. Granulomatous
inflammation is associated with foreign bodies
such as splinters, sutures, silica, and asbestos
and with microorganisms that cause tuberculosis,
syphilis, sarcoidosis, deep fungal infections, and
brucellosis.
Systemic Manifestations of
Inflammation
Under optimal conditions, the inflammatory response
remains confined to a localized area. In some cases,
however, local injury can result in prominent systemic
manifestations as inflammatory mediators are released
into the circulation. The most prominent systemic
manifestations of inflammation include the acute-phase
response, alterations in white blood cell count (leuko-
cytosis or leukopenia), and fever. Localized acute and
chronic inflammation may extend to the lymphatic
system and lead to a reaction in the lymph nodes that
drain the affected area. Painful palpable lymph nodes
are more commonly associated with inflammatory pro-
cesses, whereas nonpainful nodes are more characteris-
tic of neoplasms.
Acute-Phase Response
Along with the cellular responses that occur during
the inflammatory response, a constellation of systemic
effects called the
acute-phase response
occurs.
1,2
The
acute-phase response, which usually begins within
hours or days of the onset of inflammation or infec-
tion, includes changes in the concentrations of plasma
proteins, skeletal muscle catabolism, negative nitro-
gen balance, elevated erythrocyte sedimentation rate,
and increased numbers of leukocytes. Other mani-
festations of the acute-phase response include fever,
increased heart rate, anorexia, somnolence, and
malaise.
Acute-Phase Proteins
During the acute-phase response, the liver dramatically
increases the synthesis of acute-phase proteins such as
fibrinogen, C-reactive protein (CRP), and serum amy-
loid A protein (SAA) that serve several different defense
functions.
1,2
The synthesis of these proteins is stimulated
by cytokines, especially TNF-
α
, IL-1 (for SAA), and IL-6
(for fibrinogen and CRP).
C-reactive protein
was named because it precipitated
with the C fraction (C polypeptide) of pneumococci. The
function of CRP is thought to be protective, in that it binds
to the surface of invading microorganisms and targets them
for destruction by complement and phagocytosis. Although
everyone maintains a low level of CRP, this level rises when
there is an acute inflammatory response.
27
Recent interest
has focused on the use of high-sensitivity CRP (hsCRP)
serum measurements as a marker for increased risk of
myocardial infarction in persons with coronary heart dis-
ease.
28,29
It is believed that inflammation involving athero-
sclerotic plaques in coronary arteries may predispose to
thrombosis and myocardial infarction (see Chapter 18).
During the acute-phase response, SAA protein
replaces apolipoprotein A, a component of high-density
lipoprotein (HDL) particles (see Chapter 18). This pre-
sumably increases the transfer of HDLs from liver cells
to macrophages, which can then utilize these particles
