regeneration and repair

during the early stages (beginning) of inflammation

does repair occur at the end or beginning of inflammation?

replacement of dead cells with cells of the same lineage

what is regeneration?

regeneration

replacement of dead cells with cells of the same lineage is called _______

replacement of dead cells with CT

what is scarring?

scaring

the replacement of dead cells with CT is called _______

regeneration

scaring

when dead cells are replaced with cells of the same lineage, this is called _______.

when dead cells are replaced with CT, this is called _______

soluble factors (everything in the blood)

what factors regulate the processes of regeneration and repair?

extracellular matrix

the ______ is important for repair, and can only heal by scarring if damaged.

soluble factors

regeneration and repair is regulated by ______

no.

the extracellular matrix has the important role.

do WBCs have an important role in regeneration and repair?

-growth factors

-injury

-cell death

-tissue deformation

what can stimulate cell proliferation?

micro

sometimes the presence of the pathogen/etiological agent is not enough to stimulate

the ______environment has an important role in regeneration.

labile tissues

these are tissues that have continuously replicating cells- skin, intestinal lining, etc.

what tissues have the greatest capacity of regeneration?

tissues that have a high capacity of regeneration because their cell population is constantly replicating.

ex: skin, intestinal lining

what are labile tissues?

tissues composed of cells that are at rest (not dividing) in normal circumstances. however, they can replicate in response to a stimulus.

ex: liver

what are stable/quiescent tissues?

labile

their cells are constantly replicating, so they have a high regeneration capacity

the skin and intestinal lining are ______ tissues

stable/quiescent

the cells do not usually replicate, but can replicate in response to a stimulus

the liver is an example of a ______ tissue

tissues composed of cells with no replication/dividing capacity.

ex: heart, brain

what are permanent tissues?

permanent

they are composed of non-dividing cells, so have no regeneration capacity

the heart and brain are _______ tissues

the replacement of tissue components that are identical to those that have died

regeneration is defined as....

regeneration

the replacement of tissue components that are identical to those that have died is called...

compensatory growth- hypertrophy, hyperplasia

what are the types of regeneration that mammals can exhibit?

functional capacity;

original anatomy

with regeneration, the _________ is restored, but the ______ may not be

an intact connective tissue background.

the stroma (extracellular matrix) must not be damaged.

what is absolutely necessary for regeneration to occur?

no, the stroma cannot be damaged.

it also must have an intact CT background.

if a damaged tissue also has their stroma (extracellular matrix) that has been damaged, is it capable of regeneration?

no, the stroma cannot be damaged in order to regenerate.

instead, these lesions will be replaced by CT.

can severe lesions of both the parenchyma and stroma be regenerated?

those with severe lesions of both the parenchyma and the stroma.

they will be replaced by CT

what tissues will undergo scar formation rather than repair/regeneration?

24 hours

-fibroblast migration

-proliferation of fibroblasts and endothelial cells (for blood vessel formation)

repair begins after _____ (time). what is involved in this process?

repair (involves fibroblast migration and proliferation, + proliferation of endothelial cells)

granulation tissue formation (involves proliferation of fibroblasts and neocapillaries + fibrosis)

for a severe lesion of the parenchyma and stroma, after 24 hours, the _____ process will begin.

after 3-4 days, _____ will occur.

3-5 days

-proliferation of fibroblasts and neocapillaries

-loose extracellular matrix of CT forms → fibrosis (scar)

the granulation tissue formation occurs _____ (time) after a severe lesion to the parenchyma and stroma.

what is involved in this process?

1. angiogenesis

2. fibrosis

3. remodeling

healing consists of what 3 components?

the formation of new blood vessels.

the emission of capillary buds through preexisting vessels.

angiogenesis is...

angiogenesis

the emission of capillary buds through preexisting vessels is called ______

1. proteolysis of the basement membrane of the vessel

2. migration and proliferation of endothelial cells

3. maturation and organization of capillary tubes

what are the 3 stages of angiogenesis?

basement membrane of the vessel;

endothelial cells;

capillary tubes

angiogenesis involves the proteolysis of _______.

next, there is the migration and proliferation of _______.

lastly, there is the maturation and organization of ________.

edematous granulation tissue

this is the early stage of tissue, with many blood vessels and rubber texture,

we want this to form because it promotes the growing process.

during angiogenesis, there is a high vessel permeability, which forms......

-basic fibroblast FC (bFGF)

-vascular endothelial FC (VEGF)

what factors regulate angiogenesis?

perpendicular

new vessels always grow ______ to regular vessels

angiogenesis

-inflammatory cells

-not many cells, but lots of fibers separated by edema

what is happening in these 2 images?

fibrosis

scar formation is called....

on the meshwork of anterior granulation tissue.

it replaces the granulation tissue with fibrous tissue.

where does fibrosis occur?

granulation tissue;

fibrous tissue

fibrosis restores tissue rigidity by replacing ______ with _______

growth factors:

platelet derived GF

basic fibroblast GF

beta transforming GF

these factors are synthesized by activated endothelium and inflammatory cells

for fibrosis, what factors regulate the fibroblast migration and proliferation process?

-fibroblasts

WBCs and fibroblasts regulate this process

for fibrosis, what cells help the deposition of the extracellular matrix?

granulation tissue to scar

scar remodeling is the change from ______ to _______

protease enzyme whose catalytic mechanism involves a metal (Zn2+).

they degrade collagen and other ECM components.

they are produced by fibroblasts, macrophages, neutrophils, synovial cells, and some epithelial cells.

their synth and secretion is regulated by GF, cytokines, phagocytosis, etc.

what are metalloproteinases? what process are they a part of?

to break down the rigid scar tissue structure, to try to recreate some of the original tissue

what is the purpose of metalloproteinases?

metalloproteinases

produced by fibroblasts, macrophages, neutrophils, synovial cells, epithelial cells.

what component breaks down the rigid scar tissue structure, to try to recreate some of the original tissue?

granulation tissue

-fibroblasts

-new blood vessels

-ECM

-inflamm cells

-edema

-collagen

what type of tissue is this?

a type of new connective tissue and microscopic blood vessels that form on the surfaces of a wound during the healing process

what is granulation tissue?

scar tissue

-dense collagen fibers (CT)

-not many cells

-not much vascularization

what type of tissue is this?

scar

granulation tissue becomes ____ tissue when the collagen tissues become more organized and densely packed.

initially eliminate the offending agent.

after, they build a frame work to fill the resulting defect

the cells that reach the focus of reparation do what?

soluble growth factors and the ECM

reparation is a complex set of events directed by the interaction between.....

it is the repair of a cutaneous wound, by epithelial regeneration and scarring.

regeneration > repair

-this occurs when there is focal interruption of the basal membrane and there is only death of a few cells and little CT damage.

steps

1. exudative stage (first 24hours)

2. proliferation (day 3)

3. maturation/scar formation (week 2)

describe the process of reparation of a primary intention

primary intention

there will be epithelial regeneration and scarring.

what type of reparation occurs when there is an cutaneous wound, with only focal interruption of the basal membrane and death of few cells and little CT damage?

-fibrin occupies the incision space

-dehydration of the surface → scab

-neutrophils are in the margin

-increased mitosis of epithelial cells

it forms a wet environment that allows the migration of WBCs, cytokines, etc.

this occurs during the first 24 hours after a cutaneous wound

what occurs during the exudative stage of a primary intention?

-macrophages replace neutrophils

-granulation tissue invades incision

-many collagen fibers, which begin to bind the edges of the wound (at 5-7 days)

-continued proliferation of epithelial cells (epidermis recovers its normal thickness)

-lots of CT formation

start of angiogenesis and fibroblast migration.

this occurs 3 days after a cutaneous wound.

what occurs during the proliferation stage of a primary intention?

-accumulation of collagen

-fibroblast proliferation

-WBC infiltrate, edema, and vascularization are ↓

-"whitening" of the scar due to collagen accumulation and capillary regression

-no more fibrin

what occurs during the maturation stage of a primary intention?

-scar made of CT

-no inflamm cells

-normal epidermis

-resistance is increased up to 70-80%

after 1 month of a cutaneous wound, we see....

final stages- 1 month post injury

-no more inflamm cells

-lots of CT where the injury was

what stage of wound healing is this?

primary intention:

cutaneous wound

focal interruption of basal membrane

death of few cells

little CT damage

involves ↑ epithelial regeneration and scar formation (regeneration > scar)

secondary intention:

extensive loss of cells and tissues

scar formation > repair

↑ necrotic debris, fibrin, and exudate

↑ inflamm response

what is the difference between a primary and secondary intention?

regeneration

in a primary intention, which do we see more of, regeneration or scar formation?

scar formation

in a secondary intention, which do we see more of, regeneration or scar formation?

secondary

which- primary or secondary intention, do we see more damage, more exudate, more fibrin, more necrotic debris, and a more intense inflammatory response?

secondary intention

which- primary or secondary intention, results in a bigger area of scar tissue?

secondary

so we will see myofibroblasts

this will reduce the scar 5-10%

wound contraction is seen in _____ intention (primary/secondary)

general:

nutrition: protein deficiencies inhibit collagen synth and delay healing

immune status

circulating WBCs

hormonal factors: glucocorticoids reduce fibrosis, weakening the scar

Local:

infection

mechanical factors: pressure, torsion cause edge separation

foreign bodies: prevent healing

type of injured tissue

location of injury

what factors can influence the reparation response?

inhibits collagen synthesis and delays healing

especially seen with vitamin C deficiency (scurvy)

how does a protein deficiency impact reparation?

they reduce fibrosis, which weakens the scar

how can glucocorticoids impact reparation?

in difficult places to heal, or if there is pressure or torsion, there can be edge separation (dehiscence)

how can mechanical factors impact reparation?

infection

the most important cause of delayed healing is....

they prevent healing

how can foreign bodies impact reparation?

-minimal/absent necrosis

-removal or organization of exudate

-recovery of the normal structure/healing

if after an acute inflammation, there is a quick elimination of stimuli, what occurs?

it is either removed or organized if it cannot be removed completely.

the removal results in the recovery of the normal structure.

the organization results in healing mechanisms, which can be seen as fibrous pericarditis, for example

what happens to the exudate after acute inflammation?

fibrous pericarditis

the exudate of this acute inflammation could not be completely removed, so was instead organized and remains in the pericardium.

what do we see here?

fibrinous pericarditis

the exudate of this acute inflammation could not be completely removed, so was instead organized and remains in the pericardium.

usually fibrinous exudate is in large quantities and cannot be removed completely

what do we see here?

acute

if we see fibrinous exudate, this indicates a _______ inflammation

cellular necrosis

in tissues with permanent cells, this appears as scar formation (ex: myocardial infarct)

in tissues with stable or liable cells, this appears as regeneration and recovery of the normal structure (if the structure remained intact), or as scar formation (if the structure was destroyed)

if there is a slow elimination of stimuli after an acute inflammatory response, what happens?

if we recover from this inflammation, we can recover the lung to normal function (unless there is extensive necrosis)

this lobular pneumonia will likely be resolved in what way?

there was too much damage to be repaired, so instead the injury was isolated by encapsulation.

these hepatic abscesses occurred because....

scar tissue (hard+white)

what do we see on this heart?

chronic infarct.

at the beginning, it was red+necrotic, but has been replaced with CT, so now is whiter and harder

what happened to these kidneys?

acute

TNF and IL-1 have a bigger impact in ______ inflammation