Homeostasis

Homeostasis the maintenance of normal

physiological functions
Regulation of body temperature
Maintenance of blood pressure
Cell turnover
Tissue repair
Immune system fighting off diseases

What Does Healing Involve?

The bodys ability to repair itself is essential
It involves:
prevents excessive bleeding
removes exogenous debris
promotes new tissue deposition
allows resumption of normal physiological
processes

Regeneration vs. Scarring

There are two types of tissue repair
Regeneration
Formation of scar tissue
The type of repair depends on the tissue

How Is Healing Handled?

Through activation of a series of processes that
limit bleeding (blood coagulation)
lead to clot removal (fibrinolysis)
target foreign bacteria for removal (complement
system)
stimulate dilatation of the vasculature (kinin
system)

Inflammation and Wound Healing

The immediate response to tissue injury is inflammation
and wound healing which leads to...
migration of inflammatory cells to the wound site
release of cytokines and growth factors
activation of kinin, complement, blood clotting, and fibrinolytic
cascades

If not controlled this can lead to the deposition of

fibrous scar tissue.

Inflammation and Wound Healing

Blood Clotting & Platelet Aggregation
Soluble Blood Proteins involved in wound
healing
Hageman factor (factor XII)
fibrinogen (factor II)
Intrinsic Coagulation Pathway
torn blood vessels exposed fragments of collagen fibers
activated Hageman factor
Activated Hageman factor the intrinsic blood coagulation cas
cade an insoluble fibrin network that binds proteins and cells
together.

Inflammation and Wound Healing

Extrinsic Coagulation Pathway

Direct cell injury release of tissue factors activate

factor VII and short circuit insoluble fibrin network formation

Platelet Aggregation
In addition to protein clotting, during blood coagulation platelets
adhere to cut segments of the vessel wall and release agents such as
ADP, causing platelet aggregation.
Blood clotting and platelet aggregation work together to prevent
uncontrolled bleeding due to traumatic rupture of blood vessels.
Video clip of Coagulation Cascade
http://www.youtube.com/watch?v=cy3a__OOa2M

Inflammation and Wound Healing

Fig 13.1

Inflammation and Wound Healing

Fibrinolysis - Clot Removal
Fibrinolysis occurs when plasminogen interacts with the crosslinked fibrin network in the presence of cellular and plasma factors ,
which leads to the degradation of the fibrin network

Inflammation and Wound Healing

The Complement System
Triggered during contact with foreign materials
Involves about 11 soluble serum proteins
They can lyse bacteria
Antibody response to foreign cell surface macromolecules.
Induces an inflammatory response, so excessive complement
activation is undesirable.

Inflammation and Wound Healing

Complement System
There are two pathways by which membrane lysis can occur.
Classic pathway
triggered by an antibody-antigen complex on the foreign cell
surface
inflammation and tissue swelling
attracting white blood cells to the area of injury
Membrane lysis occurs
a full-thickness defect in the bacterial cell membrane
leads to cell death
Alternate Pathway
conversion of C3 into fragments that form active C3b.

Inflammation and Wound Healing

See this complement viedo:

http://www.youtube.com/watch?v=_iMy50AxyZE

Cells Involved In Wound Healing

Red Blood Cells
enucleated cells
surrounded by a deformable membrane
in the form of a disk
filled with the protein hemoglobin
comprise about 45% of the blood volume
circulate for about 120 day
Then they are removed by the reticuloendothelial system
Give clots thier characteristic red color

Cells Involved In Wound Healing

White Blood Cells [Leukocytes]
found at a concentration of 4,000 to 10,000 per milliliter of
blood
several sub-classifications of leukocytes
Neutrophils - 40 to 75%
Lymphocytes - 20 to 45%
Monocytes - 2 to 10%
Eosinophils - 1 to 6%
Basophils - less than 1%

Cells Involved In Wound Healing

White Blood Cells [Leukocytes] Neutrophils
Phagocytic cells that digest foreign and dead cellular and
noncellular material
Neutrophils contain granules in the cytoplasm, called lysosomes
They are used to break down bacteria
denatured proteins, and other foreign or worn-out materials
Neutrophils are found in peripheral blood and small blood
vessels
Within 12 hours of injury, they migrate to the injury sites
Undergo phagocytosis for a period of four to five days
If the injury persists for more than five days, then neutrophils are
replaced by monocytes at the wound site.

Cells Involved In Wound Healing

White Blood Cells [Leukocytes] Monocytes
Phagocytic cells that digest foreign and dead cellular and
noncellular material
Larger than other leukocytes
Released into the circulation from the bone marrow
migrate into the liver, spleen, lymph nodes, and lungs where they
comprise the macrophages of the reticuloendothelial system
In sites of injury, macrophages remove foreign and worn-out
materials by the process of phagocytosis.

Cells Involved In Wound Healing

White Blood Cells [Leukocytes] Lymphocytes
associated with immunological responses to foreign materials
subclassified as B and T cells
B (bone marrow derived) cells
are transformed on contact with foreign antigens into
plasma cells that make antibodies which bind to foreign
cells and promote cell death, or they form antibody
T (thymus derived) cells
participate in cell-mediated immunity by helping or
suppressing antibody production or by promoting cell
lysis

Cells Involved In Wound Healing

Platelets

lack a nucleus and stick to cut blood vessels

present at a concentration of 150,000 to 400,000 per milliliter of
blood
play an active role in plugging leaky vessels in conjunction with
fibrin

Wound Healing
Injury to cells and tissues as well as activation of the kinin,
complement, and fibrinolytic systems causes vasodilation, an influx of
inflammatory cells
Results in vascular permeability and the ability of white blood cells
to permeate through blood vessel walls into the wound area
Denatured collagen and fibrin degradation products help promote
migration of the white blood cells
Wound Healing clips:
http://www.youtube.com/watch?v=0TvTyj5FAaQ
http://www.youtube.com/watch?v=-_wddQWG32A

Wound Healing - Immunity

The normal defense against foreign matter consists of natural and
acquired immunity.
Natural immunity involves no prior exposure to the foreign material
and is not enhanced by exposure. This type of immunity involves the
inflammatory process, including neutrophils and macrophages.
Acquired immunity is specific and requires exposure to a foreign
material, an antigen, and is magnified by a subsequent exposure to the
antigen.

Wound Healing T Cells

T cells are characterized at different stages of development by specific
cell-surface markers including T-helper cells, T-suppressor cells,
CD4+, and CD8+.
Antibody-producing cells in the presence of T-helper cells up
regulate antibody production to foreign cells.
T-suppressor cells down regulate the production of antibodies by
plasma cells.
CD4+ T cells secrete proinflammatory lymphokines such as
interleukin 1 (IL-1) and recognize antigens on foreign cells containing
class II major histocompatibility complex (MHC) markers
CD8+ T cells secrete molecules that exert suppressor and cyto-toxic
functions, and these cells recognize class I MHC markers on foreign
cells.

Wound Healing Natural Killer Cells

Cytolytic T cells are another subset of T cells that kill target cells
expressing specific antigens on the cell membrane.
Most cytolytic T cells are CD8+ and recognize class I MHC
products expressed on the surface of foreign cells.
Cytolytic T cells react with class I MHC markers and release a
cytotoxin that leads to target cell lysis.
In comparison, a third type of lymphocyte, called null cells, include
natural killer cells (NK).
Found in blood and lymphoid tissue (lymph nodes and spleen) that
lack specific receptors for antigen recognition on the surface of foreign
cells.
NK cells possess the ability to kill certain tumor cells or cells
infected by viruses and are not antigen dependent.