Repairing

Submitted to
Dr.Ammara Saleem
Submitted by
M.Asjad Ur Rahman 6610
M.Arsal Rafiq 6619
Abdur Rehman Khan 6642
Muhammad Hashim 6643
Ali Abbas 6656
Adnan Wazir 6660
FACULTY OF PHARMACEUTICL SCIENCES
 Tissue Repair
Repairing is defined as healing, refers to the restoration of tissue
architecture and function after an injury.
it occurs by two types of reactions:
1. Regeneration of the injured tissue
2. Scar formation (deposition of connective tissue)
 Regeneration.
Some tissues are able to replace the damaged cells and essentially
return to a normal state; this process is called regeneration.
Regeneration occurs by proliferation of residual (uninjured) cells that
retain the capacity to divide, and by replacement from tissue stem
cells. It is the typical response to injury in the rapidly dividing epithelia
of the skin and intestines, and some parenchymal organs, notably the
liver.
 Role of Regeneration in Tissue Repair
• In labile tissues
In labile tissues, such as the epithelia of the intestinal tract and skin,
injured cells are rapidly replaced by proliferation of residual cells and
differentiation of tissue stem cells provided the underlying basement
membrane is intact.
The growth factors involved in these processes are not defined.
Loss of blood cells is corrected by proliferation of hematopoietic
progenitors in the bone marrow and other tissues, driven by CSFs,
which are produced in response to the reduced numbers of blood cells.
 In parenchymal organs
• Tissue regeneration can occur in parenchymal organs with stable cell
populations, but with the exception of the liver, this is usually a
limited process. Pancreas, adrenal, thyroid, and lung have some
regenerative capacity. The surgical removal of a kidney elicits in the
contralateral kidney a compensatory response that con-sists of both
hypertrophy and hyperplasia of proximal duct cells. The mechanisms
underlying this response are not understood.
 Regeneartion in liver tissues
• The regenerative response in liver is unique among all tissues after its surgical removal.
• As much as 40% to 60% of the liver may be removed in a procedure called living-donor
transplantation, in which a portion of the liver is resected from a normal person and trans-
planted into a recipient with end-stage liver disease or after partial hepatectomy performed
for tumor removal.
• In both situations, the removal of tissue triggers a proliferative response of the remaining
hepatocytes (which are normally quiescent), and the subsequent replication of hepatic
nonparenchymal cells. In experimental systems, hepatocyte replication after partial
hepatectomy is initiated by cytokines (e.g., TNF, IL-6) that prepare the cells for replication
by stimulating the transition from G0 to G1 in the cell cycle. Progression through the cell
cycle is dependent on the activity of growth factors such as HGF (produced by fibroblasts,
endothelial cells, and liver nonparenchymal cells) and the EGF family of factors, which
includes transforming growth factor-α (TGF-α) (produced by many cell types).
 Scar formation
If the injured tissues are incapable of regeneration, or if the supporting
structures of the tissue are severely damaged, repair occurs by the
laying down of connective (fibrous) tissue, a process that results in scar
formation.
 Scar Formation
Steps in scar formation
Formation of new blood vessels (angiogenesis)
Migration and proliferation of fibroblasts and deposition of
connective tissue
Maturation and reorganization of the fibrous tissue (remodeling)
 Angiogenesis
Angiogenesis is the process of new blood vessel development from existing vessels, primarily
venules.
Consists of the following steps
1. Vasodilation occurring in response to NO and increased permeability induced by VEGF
2. Separation of pericytes from the abluminal surface
3. Migration of endothelial cells toward the area of tissue injury
4. Proliferation of endothelial cells just behind the leading front of migrating cells
5. Remodeling into capillary tubes
6. Recruitment of periendothelial cells (pericytes for small capillaries and smooth muscle cells
for larger vessels) to form the mature vessel
7. Suppression of endothelial proliferation and migration and deposition of the basement
membrane
 Factors that influence the tissue repair
Tissue repair may be altered by a variety of influences, frequently
reducing the quality or adequacy of the repara-tive process. Variables
that modify healing may be extrinsic (e.g., infection) or intrinsic to the
injured tissue. Particularly important are infections and diabetes.
 Factors that influence the tissue repair
• Infection
• Nutrition
• Glucocorticoid
• Type of tissue injury
• Mechanical variables
• Poor perfusion
• Infection is clinically the most important cause of delay in healing; it prolongs
inflammation and potentially increases the local tissue injury.
• Nutrition has profound effects on repair; protein defi-ciency, for example, and
especially vitamin C deficiency inhibit collagen synthesis and retard healing.
• Glucocorticoids (steroids) have well-documented anti-inflammatory
effects, and their administration may result in weakness of the scar because of
inhibition of TGF-β production and diminished fibrosis. In some instances,
however, the anti-inflammatory effects of glu-cocorticoids are desirable. For
example, in corneal infec-tions, glucocorticoids are sometimes prescribed
(along with antibiotics) to reduce the likelihood of opacity that may result from
collagen deposition.
• Mechanical variables such as increased local pressure or torsion may cause
wounds to pull apart, or dehisce.
• Poor perfusion, due either to arteriosclerosis and diabetes or to
obstructed venous drainage (e.g., in varicose veins), also impairs healing.
• The type and extent of tissue injury affects the subse-quent repair.
Complete restoration can occur only in tissues composed of stable and
labile cells; injury to tissues composed of permanent cells must inevitably
result in scarring, as in healing of a myocardial infarct.
The
End