patho sheet #?? - by Zakaria Al-Najjar

بسم الله الرحمن الرحيم

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بسم الله الرحمن الرحيم

Healing and Repair

Fundamental to the survival of the tissue that is injured is the process of Repair.

Repair means restoration of the normal architecture and/or the function of the tissue .

*sometimes in the process of repair the architecture didn’t return to normal but the function return to normal .

Repair occurs by two processes both of them might contribute in some kinds of injury :
1. The process of repair occurs by the regeneration if the tissue that is injured is capable of regeneration & replacing of the injured tissue so this process is called regeneration.
2. the second way of repair is by the production of the scar tissue ( layers of collagen & fibrous tissue) , and this occurs if the injured tissue is incapable of regeneration or if there is sever destruction to the supporting structures of the tissue ( destruction to the extra cellular matrix ).
• the scar is not a normal tissue so the restoration may be only to the function not the architecture , so the scar tissue is only give stability to the old tissue to perform the normal function.
• We can use the term of fibrosis in the case of production of collagen in solid organs like the liver , pancreas and kidney after chronic inflammation . and we use fibrosis also in case of formation of scar tissue after myocardial infarction.
• If there is tissue space filled with inflammatory exudates ( pus ) and the repair occurs by scarring this process called organization .
• The repair involves both cell proliferation like in the regeneration & involves interaction between the cells & the extra cellular matrix .
• The control of cell proliferation :
There is three types of cells that proliferate in the process of repair :
1. the remnant of the injured tissue .
2. vascular endothelial cells which give blood vessels .
3. fibroblasts that form fibrous tissue in scar tissue.

Slide 5:
The cell cycle consists of a series of steps at which the cell checks for accuracy of the process , the aim of this is the inhibition of cell proliferation when the cell damaged so the cell cycle stop to give chance to the cell to be repaired & if the cell didn’t repaired cell apoptosis occurs to prevent the proliferation of the damaged cells .

Slide 9:
Stable cells in normal situation are quiescent ( non dividing ) but if the cell injured and growth factors released , the cell enter the cycle and cell proliferation occurs.

Slide 10:
*recently they found that some of the stem cells in the brain they proliferate and sometimes proliferation of the cardiac muscle cells after myocardial infarction occurs . but they are generally considered permanent tissue .
so if these tissues injured the repair mechanism is by scarring .

Slide 11:
In literature growth factor means the factor that increase the size of the cell .
In literature mitogen means that the factor that make the cell divide and inhibits the apoptosis ( survival ).

Slide 12 :
*each growth factor must have a receptor on the cells so the binding of the growth factor to its receptor ( ligand to the receptor ) transmit the extra cellular signal to the cell . and then induction of genes that relief the block of cell cycle and induce the proliferation of the cell.
So the growth factor signaling happens by affecting the same cell that secreted it ( this called autocrine signaling system ) , or affect the adjacent cells ( paracrine signaling system ) and this occurs in wound healing process , or affect distal cells in distal places ( endocrine signaling system ) .




Slide 17 :

The process of healing & repair depend on cell proliferation and the interaction between the cell & the extra cellular matrix .

-Extra cellular matrix :
it is a dynamic constantly remodeling macromolecule complex that is synthesized locally and will form network around the cell .

-functions of the extra cellular matrix :
1. it sequesters water so it increase the turger ( solidity ) of the tissue .
2. it sequester minerals so it give rigidity to the bone .
3. it provide substrate for cell adhesion and also it restore certain growth factors , so it is important in the cell adhesion & then in cell proliferation because of the production of the growth factor .
* so without the extra cellular matrix the body the tissues of the body will be converted into clump of cells that will be attached by neurons .

slide 18:

components of interstitial matrix :
major constituents are fibrillar & non-fibrillar collagens , as well as :
1. adhesive glycoproteins which is fibronectin .
2. water hydrated gels which are proteoglycans & hyaluornate .
3. elastin.


Components of basement membrane :
Major constituents are non-fibrillar type 4 collagen & one adhesive molecule which is laminin .

Slide 19:

The most important feature for the extra cellular matrix is scaffolding for tissue renewal .

Clarification for the meaning of scaffolding :
The normal tissue structure is maintained by the extra cellular matrix . so if the tissue injured and it is capable of regeneration & the extra cellular matrix intact , normal regeneration of the cells will happen and the maintenance of the normal architecture of the tissue will happen .
But if the hepatocytes for example injured & all the extra cellular matrix injured too then the liver will be repaired by scar formation although it is capable of regeneration . and the tissue architecture will not return to normal.

Slide 21 :

The most important adhesive glycoproteins are laminin which is formed in the basement membrane . and fibronectin which is formed in the interstitial matrix.






Slide 22 :

Fibrillar collagen : it is formed by the cross-linking of the triple helices .
And we must know the types of fibrillar collagen which are : type 1 , 2 , 3 , 5 .

Non-fibrillar collagen : like type 9 , 7 , 4
Type 9 in intervertebral disc
Type 7 in dermal – epidermal junction .
Type 4 in basement membrane .


* corrections are welcomed .



best wishes ,

done by : zakaria al-najjar