Tissue repair (need to tidy up)

Question 1

Two types of healing

Answer 1

Regeneration or scar formation

Question 2

Explain regeneration

Answer 2

Return to normal state
From surviving tissue ( especially rapidly dividing epithelia of skin and intestines eg liver)
Sometimes stem cells
Only come pcomponets fully restore themselves

Question 3

Explain scar formation

Answer 3

Connective fibrous tisse placed down instead
Provides enough stability that the tissue can still fx

Question 4

The regeneration of cells and tissues involves

Answer 4

1. Cell proliferation
2. Integrity of extracellular matrix - provides the framework for
   cell migration and maintains the correct cell polarity for the re-assembly of multilayered
   structures.
3. Development of mature cells from stem cells - skin stem cells in the bulge region of the hair follicles, in sebaceous glands and in the
   lower layer of the epidermis; small intestine stem cells located near the base of the crypt;
   corneal stem cells in the limbus

Question 5

ability of tissues to repair themselves is determined in part by their intrinsic proliferative capacity. Therefore, the tissues of the body are divided into three groups

Answer 5

Labile (continuously dividing)
Stabile tissues
Permanent tissues

Question 6

labile (continuously dividing)

Answer 6

cells of these tissues are continuously being lost and replaced by maturation from tissue stem cells and by proliferation of mature cells. These tissues can easily regenerate after injury by proliferation of residual cells and differentiation of tissue stem cells. 
Labile cells include:
 Haematopoietic cells in the bone marrow 

 The majority of surface epithelia (skin, oral cavity…) 

 Cuboidal epithelial of the ducts draining exocrine organs (e.g. salivary glands, 
pancreas, biliary tract) 

 Columnar epithelium of the GI tract, uterus, fallopian tubes 

 Transitional epithelium of the urinary tract 


Question 7

Stabile tissues

Answer 7

in these tissues are quiescent (G0 stage of the cell cycle) and have only minimal proliferative activity in their normal state. However, these cells are capable of dividing in response to injury, especially the liver.
Stable cells include:
 Cells of liver, kidney and pancreas 

 Endothelial cells  Fibroblasts 

 Smooth muscle cells
The liver has a remarkable capacity to regenerate, as demonstrated by its growth after partial hepatectomy, which may be performed for tumour resection or for living-donor hepatic transplantation.

Question 8

Permanent tissues

Answer 8

cells of these tissues are considered to be terminally differentiated and nonproliferative in postnatal life. The majority of neurons and cardiac muscle cells belong to this category. Thus, injury to the brain or heart is irreversible and results in scar. Limited stem cell replication and differentiation occur in some areas of the adult brain, and there is some evidence that heart muscle cells may proliferate after myocardial necrosis. Nevertheless, whatever proliferative capacity may exist in these tissues, it is insufficient to produce tissue regeneration after injury

Question 9

Repair by scar formation

Answer 9

Scaring damages parenchymal and epithelial cells and connective tissue framework

Question 10

Repair by connective tissue deposition consists of sequential processes that follow tissue injury and inflammation:

Answer 10

Angiogenesis: formation of new blood vessels, which supply nutrients and oxygen needed to support the repair process 


Formation of granulation tissue: characterised by migration and proliferation of fibroblasts and deposition of loose connective tissue, 

Remodelling of connective tissue with production of the stable fibrous scar. 


Not all of these events occur in every repair reaction. The repair process is influenced by many factors, including:
 The intensity and duration of the stimulus. Infection leads to persistent tissue injury and inflammation. 

 Conditions that inhibit repair, such as presence of foreign bodies or inadequate blood supply 

 Various diseases that inhibit repair (e.g. vitamin C deficiency resulting in impaired collagen formation) 


Question 11

Angiogenesis steps

Answer 11

Forming new blood vessels from branching na extension of pre-exisiting vessels

1) Separation of pericytes from the abluminal surface and breakdown of the basement 
membrane to allow formation of a vessel sprout 

2) Migration of endothelial cells toward the area of tissue injury 

3) Proliferation of endothelial cells just behind the leading front of migrating cells 

4) Remodelling into capillary tubes 

5) Recruitment of periendothelial cells (pericytes from small capillaries and smooth muscle 
cells for larger vessels) 

6) Formation of the mature vessel 


Question 12

angiogenesis is tightly regulated by growth factors and adhesion molecules

Answer 12

Vascular endothelial growth factors (VEGFs), especially VEGF-A), stimulates both migration 
and proliferation of endothelial cells 

 FGF-2 stimulates the proliferation of endothelial cells 

 Angiopoietins 1 and 2 (Ang-1, 2) play a role in angiogenesis and the structural maturation of 
new vessels 

 Ephrin mediate vascular remodelling, a process consisting of the production of a BM and 
recruitment of smooth muscle cells, pericytes, fibroblasts. 


Question 13

Formation of granulation tissue

Answer 13

Migration and proliferation of fibroblasts and deposition of loose connective tissue, together with the newly formed vessels, form granulation tissue.
The term derives from its pink, soft, granular appearance on the surface of wounds, corresponding to the formation of new small blood vessels (angiogenesis) and proliferation of fibroblasts. Granulation tissue forms by 3 to 5 days after injury.

Question 14

Maturation of the connective tissue

Answer 14

As repair continues, the number of proliferating endothelial cells and fibroblasts decreases; however, the fibroblasts progressively assume a more synthetic phenotype, with increased deposition of ECM. Collagen synthesis by fibroblasts begins within 3 to 5 days after injury and continues for several weeks. Ultimately, the granulation tissue scaffolding is converted into a scar composed of spindle-shaped fibroblasts, dense collagen, fragments of elastic tissue, and other ECM components. As the scar matures, vascular regression continues transforming the richly vascularized granulation tissue into a pale avascular scar.

Question 15

Tissue remodelling

Answer 15

Tissue remodelling phase begins 3 to 4 weeks after injury. The remodelling is essential since only the connective tissue necessary to repair the defect should be produced.Net collagen accumulation depends not only on increased collagen synthesis but also on decreased degradation. The balance between ECM synthesis and degradation results in remodelling of the connective tissue framework. Degradation of collagen and other ECM proteins is achieved by a family of matrix metalloproteinase (MMPs). They are produced by different cell types (macrophages, neutrophils, some epithelial cells, synovial cells) and released as propeptides, so requiring a proteolytic cleavage (accomplished by proteases likely to be present only at sites of injury) for the activation. Once formed, activated collagenases are rapidly inhibited by TIMPs (tissue-inhibitors of metalloproteinases) produced by most mesenchymal cells. Thus, during scar formation MMPs are activated to remodel the deposited ECM and then their activity is shut down by the TIMPs.

Question 16

Cutaneous wound healing: First intention

Answer 16

When the injury involves only the epithelial layer, the principal mechanism of repair is epithelial regeneration, also called primary union or healing by first intention.
One of the simplest examples of this type of wound repair is the healing of a clean, uninfected surgical incision approximated by surgical suture.
There is an initial haemorrhage with deposition of fibrin, leakage of plasma proteins, clot formation and platelet aggregation, associated with an acute inflammatory lesion with neutrophils followed by infiltration of macrophages that remove cell debris.
New vessels sprout and grow into the lesion and the ECM is synthesized to fill the gap. With time, this stable interconnection in the dermis is replaced by collagen fibers undergoing continual maturation. Concurrently, basal cells from both edges will undergo hyperplasia and cover the defect.
This repair leaves little trace of the wound except for mild fibrosis in the superficial dermis and loss of adnexa (sebaceous glands, hair follicles, sweat glands) at the site of the wound. The tensile strength is nearly the same as that the adjacent tissue.

Question 17

Cutaneous wound healing: second intention

Answer 17

Second intention healing occurs in septic wounds, with foreign bodies, or gaping wounds with nonopposed edges. If the wound process is disrupted or delayed, the process is shifted to second intention healing. When there is more extensive loss of cells and tissue, the reparative process is more complicated. Regeneration of parenchymal cells cannot completely restore the original architecture and abundant granulation tissue grows. Large tissue defects generate a larger fibrin clot and more necrotic debris and exudate that must be removed. So the inflammatory reaction is more intense. Moreover there are substantial scar formation and thinning of the epidermis.
. Tensile strength of granulation tissue is diminished and the lesions can tear or split with easy ulceration.