Lecture 3 PATH 300 Jan 14
Lecture 3 - Inflammation and Repair: Part 1
Inflammation is the reaction of living tissues to injury.
Injured tissue releases mediators that cause changes in the local microcirculation
providing the injured tissue.
o Microcirculation consists of an arteriole, a capillary bed, a venule, and then
connects back to circulation.
Changes are in the vessel properties
The 4 classical signs have long been known as:
o Redness, hot, swelling, and pain. A 5 sign might apparent if the inflammation is
serious enough, and it would be a loss of function.
Acute inflammation (fast onset and mild) delivers leukocytes and plasma proteins to sites of
injury. The two major components are:
1. Vascular Changes:
Specific hemodynamic changes include changes in pressure and flow of blood due to
hydrostatic pressure. Entrance to the capillary bed is through the arterioles which are
surrounded by smooth muscle. The smooth muscle can contracts or relax. (FIG) This
controls the amount of blood that flows through the vessel.
o When smooth muscle relaxes, there is increased blood flow into the
microcirculation resulting in vasodilation. The area becomes red and hot.
o Hyperemia results from a greater than normal flow of blood ( it's the opposite to
Some fluid flows
past cells on the
arteriole side and
enters back on the
venous side. As
it's going through
the tissue it
delivers gases and
Fig 1 - Schematic of the microcirculation and the leaving fluid Lecture 3 PATH 300 Jan 14
There are two main different forces acting on the fluids. The first main pushing force is
hydrostatic pressure. It's highest on arteriole side so fluid can flow out into the tissue.
The force acting to keep fluid inside the vessels or draw it in is the osmotic pressure.
o Not all of the fluid that exits the microcirculation comes back on the venous side.
Some excess fluid is drained in the lymphatic system.
If the fluid flowing out is protein-free it is called transudate. Under acute inflammation
you lose some of the
plasma proteins and the
fluid is then called
exudate (2-4). Tissue
with exudate is much
more swollen Proteins
leave the vasculature via
spaces between the
endothelial cells. This is
a normal process that
happens under injury.
However the more
serious the injury is to
the endothelial cells, the
more destructive it is
and the spaces become
too big and many
components leak out. Contraction of endothelial cells increases the spaces between them
and is the due to the action of vasoactive mediators.
Fig 3 - Schematic of the exudate and transudate
Net flow out increases on the venous side during
Mild inflammation: only the venule will contract and increase in permeability takes place.
Mast cells are located right next to blood vessels and release vasoactive mediators. One
of them is histamine
o Histamine acts on both sides of capillary bed. It causes vasodilation of arterioles
(the area becomes red) and contraction of endothelial cells in venules so you get
During extensive inflammation all of the microcirculation dilates.
The transient permeability of the microcirculation is minor and due to mast cells. In
sustained injury the swelling lasts longer, but there's a delayed prolonged reaction. The
cause of the injury doesn't cause swelling right away but the synthesis of more mediators
which are released later on, so you don't get redness and pain during injury. You don't Lecture 3 PATH 300 Jan 14
know you are being damaged. For example, you don't turn red from a sunburn right
away but when you get home.
2. Cellular: accumulation of leukocytes
At the capillary level, the flow of cells is such that smaller cells flow in the middle
and larger against the vessel walls. During inflammation, different mediators cause
the larger cells stick to the endothelial cells and eventually get out into the tissue.
RBCs and platelets stay in circulation while leukocytes enter tissue
Normal laminar flow means leukocytes are in contact with the endothelial cells. As
inflammation begins and fluid flows out, the concentration of cells increase together
and leukocytes are pushed more firmly against the walls. Leukocytes interact with
endothelial cells with selectins
Selectins stick to the endothelial cells with their extensions. This interaction is not
very strong so they detach often. The results in them trolling along the endothel