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Medical Pathophysiology > Week 2 - Lecture 2 - Healing, Tissue Repair and Chronic Inflammation > Flashcards

Week 2 - Lecture 2 - Healing, Tissue Repair and Chronic Inflammation Flashcards

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USMLE® Step 1 flashcards
1
Q

goal of tissue healing and repair

A

cover the wound
clear debris
restore structural integrity
restore functional integrity

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2
Q

3 phases of healing and tissue repair

A

inflammatory
proliferative
remodelling

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3
Q

covering the wound and clearing the debris

A

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
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4
Q

restoring structural integrity

A

construction of new cells and tissues requires growth factors and matrix proteins

extracellular matrix (ECM) is required

  1. basement membrane
  2. connective tissue layers
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5
Q

Basement membrane (BM) is needed for

A

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

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6
Q

restoring structural integrity pt.3

A

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
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7
Q

Restoring structural integrity pt.4

A

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

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8
Q

restoring functional integrity pt.5

A

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
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9
Q

Resolution : restoring functional integrity

A 
healing response to mild injury 
minimal disruption 
-scratch, mild sunburn 
healing is rapid 
resolution: "business as usual"
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10
Q

Restoring functional integrity pt. 6

A

labile : constantly regenerate
stable: stop regenerating, but can resume regeneration
permanent : do not regenerate

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11
Q

replacement : restoring functional capacity

A

regeneration can only happen if cells can undergo mitosis

  1. proliferation : growth and reproduction
  2. differentiation : cells mature and specialise OR
  3. 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
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12
Q

Replacement : restoring functional integrity

A
  1. regeneration not possible
  2. 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
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13
Q

cutaneous wound healing by intension : primary

A

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

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14
Q

conditions that promote wound healing

A

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
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15
Q

secondary : cutaneous wound healing by intention

A

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

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16
Q

complications of healing

A 
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
17
Q

dysfunctional wound healing

A 
dysfunction during inflammatory response 
-infection 
-inadequate perfusion 
  - ulceration 
dysfunction during reconstructive phase 
- impaired collagen synthesis 
  - keloid scar
  - dehiscence 
  - adhesions
18
Q

Complications of healing : ulcerations

A

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
19
Q

Complications of healing : dehiscence

A

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
20
Q

complications of healing : keloids

A

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

21
Q

complications of healing ; adhesions

A

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
22
Q

Chronic inflammation

A

acute inflammatory and immune responses are unsuccessful
recurrent or persistent inflammation, lasting several weeks or longer
formation of granulomas and scarring often occur

23
Q

Cells of chronic inflammation

A

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
24
Q

granuloma formation

A

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

25
Q

granuloma formation pt2

A

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
26
Q

general manifestations

A

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

Medical Pathophysiology (30 decks)

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