BASIC PATHOLOGY

REPAIR. CELL GROWTH AND REGENERATION. WOUND HEALING.

-proper healing needs previous removal of inflammatory and necrotic
cell debris
resolution -removal of debris associated with a complete restoration of the
tissue to preinjury state
regeneration - complete replacement of necrotic parenchymal cells by new
parenchymal cells of the same quality
-resolution and regeneration- ideal outcome of healing- is possible only in the
tissues with prevailing labile cells (cells capable of mitotic division- complete
regeneration)
-if complete resolution and regeneration is not possible, necrotic foci may be
replaced by collagen, this process is termed organisation repair by scar
formation
- mechanism of healing depends on the type of inflammation, the extent of
necrosis, regenerative capacity of damaged cells, rate of lymphatic flow,
amount of fibrin in the inflammatory exudate etc.
REGENERATION
-replacement of lost parenchymal cells is dependent on
1-regenerative capacity of the cells
2-number of surviving cells
3-maintenance of basement membranes or presence of stem cell layer
The cells of the body can be divided into 3 groups on the basis of their
regenerative capacity and their relation to the cell cycle:
1.- Labile cell (intermitotic)
2.- Stable cell (reversible postmitotic )
3.- Permanent cell (irreversible postmitotic)
1.- Labile cells- continuously dividing cells- they continue to proliferate,
remain all the time in cell cycle
-Healing in tissues with many labile cells:
-injury is followed by rapid and complete regeneration
-surgical removal of endometrium by curettage is followed by
complete regeneration from the basal germinative layer within short
time
-or destruction of erythrocytes stimulates rapid erythroid hyperplasia in
bone marrow which results in complete regeneration of erythropoesis
2.-Stable cells-quiescent- they are considered to be in G0 phase, may
undergo rapid proliferation after appropriate stimuli, they may be recruited
back to the cell cycle
Healing in tissues with prevailing stable cells:
-regeneration in tissues with most stable cell is possible but the following
conditions must be fulfilled:
-sufficient amount of viable tissue must remain

- intact fibrous interstitial network and original basement membranes

preserved
-if complete necrosis involves both parenchyma and interstitium- no
regeneration is possible and necrosis heals by scar formation
3.- Permanent cells- non-dividing. cells have no regenerative capacity
Healing in tissues with permanent cells:
-injury to tissue with permanent cells is always followed by scar formation,
no regeneration is possible.
REPAIR BY SCAR FORMATION.
scar=mass of collagen that is the final result of the process of organization
repair by scar occurs:
- if resolution fails
- if the injurious agent continuously causes injury in chronic
inflammation
- if parenchymal necrosis cannot be repaired by regeneration because
of prevalence of permanent cells
Process of repair by scar formation has several steps:
1- Preparation - the tissue is prepared by removal of the inflammatory
exudate. Debris is liquefied by lysosomal enzymes derived of neutrophil
leukocytes, liquefied material is removed by lymphatics, residual particle are
phagocytosed by macrophages
2- Ingrowth of granulation tissue
-granulation tissue is highly vascularized connective tissue composed of
newly formed capillaries, proliferating fibroblasts and myofibroblasts, cell
debris and residual inflammatory cells
-major role of the granulation tissue is to occupy the tissue defects lost
by injury
grossly- granulation tissue is deeply red (because of numerous capillaries)
and soft, with granularity of the surface
3- Collagenization
-collagens are the major fibrillary extracellular proteins.
Classification of collagens:
-types I and III collagens - interstitial types of collagen, ubiquitous,
most common in connective tissues, scars, stroma of tumours, stroma of
normal organs
-type II collagen - major collagen of cartilage
-type IV collagen - one of major constituents of BMs ( in addition to
laminin, entactin and heparan sulphate )
type V collagen - collagen of so called anchoring fibrils of BMs of
epithelia
-collagens types VI- XIII - are minor constituents of either connective
soft tissues or cartilage
The most important in scar formation are interstitial collagens type III
and I- type III composed of thin fibers, synthesised by young fibroblasts and

myofibroblast in granulation tissue, on the other hand, type I collagen

prevails in mature scar.
4- Maturation of the scar
-collagen content of granulation tissue progressively increases with the time,
particularly the amount of type I collagen increases
-the scar becomes less cellular and less vascular
-the mature scar is composed of hypovascular poorly cellular collagenous
mass- composed mostly of collagen type I
5- Contraction and strengthening
-contraction decreases the size of scar- allows optimal function of the
remaining tissue
HEALING OF SKIN WOUNDS.
1-Healing by first intention (primary union)healing of clean
uninfected surgical incision joined by surgical sutures
-limited number of dead cells, minor discontinuity of basement membrane
-the incisional space immediately fills with clotted blood containing fibrin
-within 24 hrs-neutrophils appear, there is an increased proliferation in basal
layer of epidermis at the margins of the wound - epithelial cells migrate and
synthesise basement membrane
-day 3- leukocytes disappear and the are replaced by macrophages granulation tissue progressively invades the incision space, collagen fibres
are already present but do not cross completely the incision space, and the
epithelial cells continue to proliferate
-day 5- the incision space is filled with granulation tissue, collagen fibres are
abundant and begin to bridge the incision, epidermis recovers to normal
thickness, there is a maturation of the epidermis
-2nd week- accumulation of collagen continues, but proliferation of
fibroblasts and leukocytes slow down,
- oedema, fluid, and necrotic cells mostly have disappeared, and there is a
regression of vascular channels
-end of the 1st month- scar covered by intact epidermis is finished
-the scar is composed of mature collagenous connective tissue devoid of
inflammatory infiltrate
2- Healing by second intention ( secondary union )
healing by second intention differs from primary healing in several aspects:
-large tissue defects, such as large infarctions, ulcerations, abscesses,
large wounds- have always more fibrin in exudate, thus more intense
inflammatory reaction
-much greater amount of granulation tissue is formed
-final scar is much smaller than original wound due to wound
contraction (mostly results of activities of myofibroblasts ) - tissue retraction
PATHOLOGIC ASPECTS OF REPAIR.
-Cell growth and fibroplasia are the most important aspects in healing-these processes of healing may be modified by pathologic state:
The factors that modify the quality of tissue repair include:

-nutrition deficiency, particularly vitamin C deficiency decreases the

ability to heal wounds
-glucocorticoids have anti-inflammatory effect
-persistent infection is the most important cause of delayed healing
-mechanical factors, as wound dehiscence
-low blood supply, presence of foreign bodies
-disorders of lymphatic flow may slow down the removal of necrotic
cells and cause delayed healing
-the presence or absence of diabetes mellitus and other underlying
diseases
-adequate levels of circulating white blood cells
-type of injured tissue - perfect repair may occur only in tissues built
up of labile and stable cells, while injuries to permanent cells results in
scarring, such case is myocardial infarction ( no regeneration of specialised
heart muscle elements )
-large amounts of exudate slows down a healing healing of exudate include:
-digestion of the exudate initiated by proteolytic enzymes of leukocytesresorption of dissolved exudate= process called resolution
-the presence of extensive necrosis or large amounts of fibrin in the exudate
or low blood and lymphatic rate -the process of resolution cannot occur and
the exudate is replaced by granulation tissue and transformed into fibrous
tissue (organization of exudate )- for example lung carnification in pathologic
healing of pneumonia
-aberration of growth -hyperplastic scarring- if excessive amounts of
collagen accumulate within the scar= keloid
-keloid formation appears to an individual predisposition of unknown
reasons or excessive formation of granulation tissue= exuberant granulation
- granulation tissue protrudes over the surface of the wound and in fact
blocks the reepithelization- granulation tissue must be removed surgically.