Cardinal signs of inflammation
In the scenario with a bee sting: you will see redness (Tubor). The king of vasodilators is
histamine and it vasodilates the arterioles. Therefore, histamine is responsible for the redness of
acute inflammation (ie bee sting), and is working on arterioles. Now if we felt the area, it will be
warm (Calor = heat), this is due to vasodilating the arterioles, which is caused by histamine. For
example in endotoxic and septic shock, the skin is warm b/c you are vasodilated. Tumor is a
raised structure caused by histamine. Histamine can lead to increased vessel permeability in the
venules; is arterial thicker than venules? Yes. The venules are very thin; they basically have an
endothelial cell with a basement membrane, all you have to is drill a hole through the BM and
you are out. Therefore, increased vessel permeability occurs at the venule level, not the arterial
level. Histamine contracts the endothelial cells, and leaves the BM bare, leading to increased
vessel permeability, producing an exudate, and swelling of tissue, hence tumor of acute
inflammation. The area may hurt (Dolor = pain) but hitamine does not have anything to do with
this. Bradykinin is part of the kininogen system between factor 11 and Hageman factor 12. So
when you activate the intrinsic pathway, you automatically activate the kininogen system.
When you activate factor 12 (Hageman factor), it will activate 11 and the whole kininogen
system. The end product is bradykinin. ACE degrades bradykinin. Complication of ACE inhibitor
is angioedema. Also inhibit metabolism of bradykinin, which increases vessel permeability,
producing the angioedema (swelling of the tissues). How bradykinin produces cough is not
really understood. Bradykinin and PGE2 cause pain (dolor) and is the only one out of the four
Latin terms of acute inflammation that is not due to histamine release.
Steps involved in Acute inflammation (this the normal sequence in acute inflammation):
1. Emigration: includes margination, paveenting, rolling, adhesion, and transmigration
Neutrophils in circulation start to become sticky b/c of adhesion molecule synthesis.
Endothelial cells begin to synthesize adhesion molecules. Eventatually, neutrophils will stick
to endothelial cells, these steps are called pavmenting or margination. Then neutrophils
look for bare basement membrane on the venules and then they drill a hole through it via
type 4 collagenase. Cancer cells also have type 4 collagenase, that’s how they metastasize.
Cancer cells attach to endothelial via adhesion molecules, usually against laminin in BM, and
they have collagensae to get through the BM, therefore, cancer cells are pretty much like a
neutrophil when invading tissue.
When they pass BM of small venules, they emigrate but they have to know what direction
to go. They get directions in a process called directed chemotaxis. C5a and LT-B4
(leukotriene B4) are the chemotactic agents. These chemotactic agents are also involved in
making adhesion molecules on neutrophils). Therefore, they make adhesion molecules AND
give direction by acting like chemotactic agents.
3. Phagocytosis via opsonization:
a) Example: in an acute inflammation with staph aureus, the bacteria are being processed
by opsonins, which immobilize the particles on the surface of the phagocyte. The two main
opsonins are IgG and C3b. They help with phagocytosis. b) Example of an opsonization defect: Brutons agammaglobinemia: an x-linked recessive
dz, where all the immunoglobulins are missing, including IgG. Therefore, MCC death in these
pts is due to infection b/c cannot opsonize things. It produces hypogamma-globinemia, but
the mechanism of infection is due to not having IgG to opsonize bacteria, therefore cannot
Bacteria are opsonized by IgG and C3b, which means that neutrophils must have receptors
for those. In acute inflammation the main cell is neutrophil and in chronic inflammation the
main cell is macrophage/monocyte (monocytes become macrophages). These cells have to
have receptors for these opsonins (IgG and C3b). Then they become phagocytosed or
become phagolysomes. When they are phagocytosed, the lysosomes go to microtubules
and empty their enzyme into this.
c) Example: In I-cell disease: in this dz, mannose residues cannot be phosphorylate in golgi
apparatus therefore the enzymes are not marked with phosphorus, and the lysosome are
4. Intracellular microbial killing:
(1) Staph aureus in hottub surrounded by enzymes
(2)Chlamydia can get out of phagolysosome, mechanism unknown, but sometimes they
have mucous and all kinds of things around them.
b) O 2ependent myeloperoxidase system is the boards!!
Molecular O i2 converted by NADPH oxidase, which is in the cell membrane of neutrophils
and monocytes, but not mac