Week 2 - Lecture 2 - Healing, Tissue Repair and Chronic Inflammation Flashcards
goal of tissue healing and repair
cover the wound
clear debris
restore structural integrity
restore functional integrity
3 phases of healing and tissue repair
inflammatory
proliferative
remodelling
covering the wound and clearing the debris
at the time of injury: homeostasis is triggered
vasoconstriction and clot formation
protective scab formation (thrombus) : dried blood and exudate
- physical barrier to prevent further harmful substances to enter
- prevents the loss of plasma
- epithelial cells regenerate under the thrombus
neutrophils move into injured area first
macrophages follow
- digest, remove harmful substance/debris
- necrotic cells and tissue must be removed before healing can start
restoring structural integrity
construction of new cells and tissues requires growth factors and matrix proteins
extracellular matrix (ECM) is required
- basement membrane
- connective tissue layers
Basement membrane (BM) is needed for
to provide architectural structures
support re-epithelialisation, movement of epithelial cells to form covering
store growth factors
restore neuromuscular function
support development of parenchymal tissue : made up of cells with specific function (i.e.. neurons, myocardial cells, epithelial cells)
BM is reproduced by cells according to injury site
- endothelial, epithelial, muscle, adipose, Schwann cells etc
BM must be reproduced first
- extensive damage delays re-epithelisation
restoring structural integrity pt.3
connective tissue layer (stromal or intestinal tissue)
- collagen, elastin, glycoprotein
- (material that fills the space between cells)
Function - storage of proteins -exchange medium between proteins and other cells -architectural support physical protection of organs
cells of connective tissue
- fibroblasts, adipose cells, endothelial cells, osteocytes, chondrocytes
- stimulate replacement of damaged connective tissue
Restoring structural integrity pt.4
damaged basement membrane and connective tissue layers must be replaced
-structure and function
Temporary extracellular matrix is formed after injury : proteins from plasma (PM)
Provisional matrix (PM)
- decrease blood and fluid loss
- attract and support fibroblasts, endothelial and epithelial cells
Granulation tissue : PM is converted by macrophages
- macrophages, fibroblasts
- angiogenesis (re-vascularisation), new blood vessels: oxygen, nutrient supply, waste removal
- extensive network of capillaries
As wound heals, no longer needed
-reabsorbed
restoring functional integrity pt.5
major goal off healing : restore functional integrity of parenchymal tissue (tissue with specific function)
if functional integrity not restored: functional loss
3 processes
- resolution
- regeneration
- replacement
Resolution : restoring functional integrity
healing response to mild injury minimal disruption -scratch, mild sunburn healing is rapid resolution: "business as usual"
Restoring functional integrity pt. 6
labile : constantly regenerate
stable: stop regenerating, but can resume regeneration
permanent : do not regenerate
replacement : restoring functional capacity
regeneration can only happen if cells can undergo mitosis
- proliferation : growth and reproduction
- differentiation : cells mature and specialise OR
- diapedesis : migration of nearby similar cells
labile cells often regenerate
- skin : re-epithelialisation
- epithelial cells in the periphery divide and migrate inward
- basement membrane is needed
stable cells regenerate when required
- injury/surgery of liver : 80% loss
- 6-12 months later former size
Replacement : restoring functional integrity
- regeneration not possible
- extensive wound
permanent cells:
do not undergo mitosis
- neurons, skeletal, cardiac muscle, lens of eye
functional tissue is replaced with connective tissue
labile/stable cells : extensive injury
- severe burn
- connective tissue scar replaces epithelial tissue
- fills the gap, does not function
cutaneous wound healing by intension : primary
specific sites exhibit different repair patterns
(skin, liver, kidney, lung, heart, nervous system etc)
small wounds with approximated edges heal by primary intention
- edges are close together
- paper cut
- surgical incision
heal quicker and easier
- minimal cell proliferation and neurovascularisation
wound is closed with all areas
-connecting and healing at the same time
risk of infection is reduced
scarring is minimal
conditions that promote wound healing
wound healing depend primarily
- adequate vascular inflammatory response
- adequate cellular inflammatory response
- reformation of extracellular matrix
- regeneration of cells capable of mitosis
adequate dietary intake
- proteins, carbohydrates, fats, vitamins, minerals
- proteins : required during every phase
- vitamins A and C: re-epitheliasation and collagen synthesis
adequate blood flow
- transporting inflammatory cells to healing site
- transporting nutrients, oxygen
secondary : cutaneous wound healing by intention
large, open wounds
must heal by secondary intention
from bottom up
- extensive cell proliferation and granulation tissue
-wound is re-epithelialised from margins
collagen fibres are deposited into granulation tissue
-granulation tissue is reabsorbed and replaced by scar
risk for infection and scarring
complications of healing
impaired wound healing can happen at any point of the healing process primary factors affecting wound healing -ineffective inflammatory response -inadequate nutritional status -poor tissue perfusion
dysfunctional wound healing
dysfunction during inflammatory response -infection -inadequate perfusion - ulceration dysfunction during reconstructive phase - impaired collagen synthesis - keloid scar - dehiscence - adhesions
Complications of healing : ulcerations
ulcer: lack of adequate perfusion
- crater like lesion on skin or mucous membrane
- persistent inhabitation by microorganism
- resistent to healing
skin ulcer
- pressure ulcer (decubitus ulcer) of the skin, commonly found diabetic patients
- the histologic slides show a skin ulcer with a large gap between edges of the lesion, a thin layer of epidermal reepithelialisation and extensive granulation tissue formation in the dermis
Complications of healing : dehiscence
problem of deficient scar formation
wound splits open
- opens area to invasion of microorganism, infection
early after surgery
- mechanical stress (coughing, movement)
- possible complication after surgery
later in recovery period
- poor development of extracellular matrix
- inadequate collagen
complications of healing : keloids
opposite of dehiscence
hypertrophic scars: excessive collagen production at the site of injury
- cosmetic problem
-removal often result in another keloid
- higher frequency in those with deeply pigmented skin
- between 10-30 year old with familial disposition to developing keloids
complications of healing ; adhesions
adhesion : impaired collagen deposition
- fibrous connections form between serous cavity and nearby tissue
main risk is due to abdominal surgery - collagen fibres connect organs with peritoneum (bowel, bladder, ovaries) -Restrict free movement of organ -Pain -Loss of organ function
Chronic inflammation
acute inflammatory and immune responses are unsuccessful
recurrent or persistent inflammation, lasting several weeks or longer
formation of granulomas and scarring often occur
Cells of chronic inflammation
cellular activity is different between acute and chronic inflammation
- longer lasting activity of certain cell is more prominent
- monocytes/macrophages
- -lymphocytes
monocytes circulate in blood, mature into macrophages in the tissue
macrophages
- produce proteinases: enzymes that destroy elastin and tissue components
- break down dead tissue
- break down healthy tissue
- ongoing tissue destruction at and surrounding site
- active fibroblasts: responsible for collagen production
- extensive scarring
- permanent loss of function
- deformity of tissue or organ
granuloma formation
in some cases : chronic inflammation results in granuloma formation
granuloma
- nodular inflammatory lesion
- encase harmful substance
formation is regulated macrophages
they form when
- injury causing agents are difficult to control
- injury causing agents are poorly digested
foreign bodies (splinters, sutures, silica, asbestos)
certain microorganisms (tuberculosis, syphilis
granuloma formation pt2
macrophages protect healthy tissue by forming granuloma
- adapt into giant cells : phagocytes that can engulf larger particle than macrophages
- adapt into epitheloid cells : form a fibrotic wall
phagocytosis of harmful substances continues inside : necrotising granuloma
- necrotic cells fill the inside of granuloma
- necrotic content diffuse through granuloma wall
- only fibrotic capsule remain
general manifestations
during flare-up of symptoms
- same as acute inflammation
- 5 cardinal signs : redness/swelling/pain/loss of function
- may lead to scarring, granuloma formation
- other systemic manifestations
- fever
- anaemia
- malaise
- weakness
- fatigue
- anorexia
- weight loss
during remission of chronic inflammation: no symptoms
