Regeneration And Repair Flashcards

1
Q

What is regeneration?

A

Regrowth of cells (with minimal evidence of injury)

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2
Q

When is regeneration possible?

A

Minor skin injuries (superficial skin incision/abrasion)

Physiological (blood cells in bone marrow)

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3
Q

Where do new cells come from?

A

Stem cells - replace dead and damaged cells

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4
Q

Types of stem cell

A

Totipotent - produce any cell (embryonic)
Multipotent - produce several types of cell (haemopoetic)
Unipotent - can produce one cell type (epithelial)

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5
Q

Example of stem cell locations

A

Epidermis - basal layer
Intestinal mucosa - bottom of crypts
Liver - between hepatocytes

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6
Q

Tissue regeration types

A

Labile
Stable
Permanent

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7
Q

Labile tissue

A

Continuous replication - always in cell cycle

Epithelium, haemopoetic tissue

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8
Q

Stable tissue

A

Low level of replication but can undergo rapid if injured - G0 of cell cycle (left but can re enter)

Liver, kidneys, pancreas, bone

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9
Q

Permanent tissue

A

No replication - left cell cycle and cannot re enter

Neurones, skeletal muscle, cardiac muscle

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10
Q

What does regeration require?

A

Intact conncective tissue architecture (to build upon)

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11
Q

What is fibrous repair?

A

Replacement of functioning tissue with a scar

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12
Q

When does a scar form eg fibrous repair?

A

Necrosis of permanent tissues
Collagen framework has been destroyed
On going chronic inflammation

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13
Q

4 stages of fibrous repair (scar formation)

A

Bleeding and haemostasis
Inflammation
Proliferation
Remodelling

BIPR

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14
Q

Bleeding and haemostasis stage

A

Prevents blood loss
Clot formed

Seconds - minutes

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15
Q

Inflammation stage

A

Acute then chronic
Digestion of blood clot and necrotic tissue (macrophage)

Minutes - days

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16
Q

Proliferation stage

A

Angiogenesis
Fibroblasts, myofibroblasts and extracellular matrix proliferates

Granulation tissue formed

Days - weeks

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17
Q

What is granulation tissue?

A

Fills gap - prevents pathogen entry
Capillaries can suplly oxygen and nutrients (angiogenesis)
Contracts (myofibroblasts) and closes wound

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18
Q

How can granulation tissue appear?

A

Pale yellow and shiny

Lots of ECM and branching immature blood vessels (eliptical) on H&E

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19
Q

Remodelling phase

A

Maturation of scar

Reduced cell population, increased collagen, myofibroblasts contract

Fibrous scar forms
Weeks - years

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20
Q

Cells involved in fibrous repair

A

Neutrophil & macrophage - phagocytosis, release inflammatory mediators

Lymphocyte - eliminate pathogens, co ordinate other cells

Endothelial cell - proliferation and angiogenesis

Fibroblast - secrete collagen and elastin (form ECM)

Myofibroblast - fibroblast+smooth muscle = wound contraction

21
Q

How do fibroblasts and myofibroblasts appear on H&E?

A

Spindle shaped (elongated) nucleus

Star shape cytoplasmic projections (cant usually see)

22
Q

Collagen stages names

A

Pre-pro collagen
Procollagen
Tropocollagen

23
Q

Step 1 collagen synthesis

A

In ER of (myo)fibroblasts

Polypeptide alpha chain (pre pro collagen)
Gets hydroxylated (Vit C dependent)

Forms procollagen

24
Q

Step 2 collagen synthesis

A

Into cytosol

Alpha chains cross link to form triple helix

25
Q

Stage 3 of collagen synthesis

A

Pro collagen leaves cell—> extracellular

C and N terminals cleaved off

Forms tropocollagen

26
Q

Stage 4 collagen synthesis

A

Tropocollagen cross linked

Microfibrils —> fibrils —> fibres

27
Q

Collagen synthesis overall

A
ER:
Preprocollagen 
Hydroxylation 
Procollagen 
Triple helix 
Extracellular:
C and N terminals cleaved off
Tropocollagen formed
Tropocollagen cross linked
Forms fibrils —> fibres
28
Q

Diseases of defective collagen

A

Scurvy

Inherited:
Ehlers-Danlos
Osteogenesis Imperfecta
Alport syndrome

29
Q

Scurvy - why?

A

Vitamin C deficiency

Unable to hydroxylate pre-procollagen

Defective triple helix and defective collagen

30
Q

Scurvy symptoms/signs

A

Poor wound healing
Bruising
Bleeding of gums
Tooth loss

31
Q

Ehlers Danlos syndrome

A

Collagen fibres lack tensile strength

Poor wound healing
Joint dislocation
Hypermobile joints
Rupture of colon/organs/arteries

32
Q

Skin Ehlers Danlos

A

Hyperextensible
Fragile
Suceptible to injury

33
Q

Osteogenesis imperfecta

A

Brittle bone disease
Skeletal fragility - little bone tissue

BLUE SCLERA - too little collagen so is not transparent
Hearing impairment
Dental abnormalities

34
Q

Alport syndrome

A

X linked - MALE MORE AFFECTED

Type 4 collagen affected

Dysfunction of glomerulus basement membrane, cochlea of ear, lense of eye

Blood in urine, chronic renal failure (deafness, eye disorders)

35
Q

How is regenration controlled?

A

Direct cell contact
Local mediators (growth factors)
Hormones

36
Q

Cell to cell contact

A

Contact inhibition - isolated cells replicate until they encounter other cells

Cadherins bind and prevent proliferation

37
Q

Cancer cell to cell contact

A

Cadherins are defective

Continued proliferation = multilayers

38
Q

Growth factors

A

Polypeptides that act on cell surface receptors

Cause cell to enter cell cycle —> proliferate

39
Q

Growth factor examples

A

Epidermal GF
Vascular Endothelial GF
Platelet derived GF
Tumour necrosis factor

40
Q

Two types of skin healing

A

Primary intention

Secondary intention

41
Q

Primary intention

A

Apposed edges (near eachother/sutured)

Minimal clot/granulation tissue = small scar

Epidermis regenerates, dermis fibrous repairs

42
Q

Secondary intention healing

A
Unapposed edges (infection/ulcer/abcess)
Significant tissue loss = lots of contraction needed

Abundant clot, inflammation, granulation tissue
Dermis - repair
Epidermis regenerates from edges

43
Q

Fracture healing stages

A

Haematoma (granulation)

Soft callus (fibrous/cartilage) woven bone

Hard callus (woven bone to lamellar bone)

Remodelling (original outline)

44
Q

How long for soft and hard callous formation?

A

1 week soft

Several weeks hard

45
Q

How long for a fracture to be completely remodelled?

A

Months/years

46
Q

Local factors influencing wound healing

A
Size
Location
Blood supply
Infection
Foreign bodies
47
Q

Systemic factors influencing wound healing

A
Age
Anaemia/hypoxia/hypovolaemia (less O2)
Obesity
Diabetes (neuropathy/vessel damage)
Drugs 
Vitamin deficiency (Vit C)
Malnutrition
48
Q

Complications of fibrous repair

A

Insufficient fibrosis - dehiscence (opening)
Excessive fibrosis - keloid scar

Adhesions - fibrous bands (can obstruct tubes)

Loss of function/architecture

Excessive contraction - constriction of tubes
Fixed flexion (contractures)
49
Q

When does insufficient fibrosis often occur?

A

Obese
Elderly
Malnutrition
Steroid use