Regeneration And Repair

Question 1

What is regeneration?

Answer 1

Regrowth of cells (with minimal evidence of injury)

Question 2

When is regeneration possible?

Answer 2

Minor skin injuries (superficial skin incision/abrasion)

Physiological (blood cells in bone marrow)

Question 3

Where do new cells come from?

Answer 3

Stem cells - replace dead and damaged cells

Question 4

Types of stem cell

Answer 4

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

Question 5

Example of stem cell locations

Answer 5

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

Question 6

Tissue regeration types

Answer 6

Labile
Stable
Permanent

Question 7

Labile tissue

Answer 7

Continuous replication - always in cell cycle

Epithelium, haemopoetic tissue

Question 8

Stable tissue

Answer 8

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

Liver, kidneys, pancreas, bone

Question 9

Permanent tissue

Answer 9

No replication - left cell cycle and cannot re enter

Neurones, skeletal muscle, cardiac muscle

Question 10

What does regeration require?

Answer 10

Intact conncective tissue architecture (to build upon)

Question 11

What is fibrous repair?

Answer 11

Replacement of functioning tissue with a scar

Question 12

When does a scar form eg fibrous repair?

Answer 12

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

Question 13

4 stages of fibrous repair (scar formation)

Answer 13

Bleeding and haemostasis
Inflammation
Proliferation
Remodelling

BIPR

Question 14

Bleeding and haemostasis stage

Answer 14

Prevents blood loss
Clot formed

Seconds - minutes

Question 15

Inflammation stage

Answer 15

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

Minutes - days

Question 16

Proliferation stage

Answer 16

Angiogenesis
Fibroblasts, myofibroblasts and extracellular matrix proliferates

Granulation tissue formed

Days - weeks

Question 17

What is granulation tissue?

Answer 17

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

Question 18

How can granulation tissue appear?

Answer 18

Pale yellow and shiny

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

Question 19

Remodelling phase

Answer 19

Maturation of scar

Reduced cell population, increased collagen, myofibroblasts contract

Fibrous scar forms
Weeks - years

Question 20

Cells involved in fibrous repair

Answer 20

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

Question 21

How do fibroblasts and myofibroblasts appear on H&E?

Answer 21

Spindle shaped (elongated) nucleus

Star shape cytoplasmic projections (cant usually see)

Question 22

Collagen stages names

Answer 22

Pre-pro collagen
Procollagen
Tropocollagen

Question 23

Step 1 collagen synthesis

Answer 23

In ER of (myo)fibroblasts

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

Forms procollagen

Question 24

Step 2 collagen synthesis

Answer 24

Into cytosol

Alpha chains cross link to form triple helix

Question 25

Stage 3 of collagen synthesis

Answer 25

Pro collagen leaves cell—> extracellular C and N terminals cleaved off Forms tropocollagen

Question 26

Stage 4 collagen synthesis

Answer 26

Tropocollagen cross linked Microfibrils —> fibrils —> fibres

Question 27

Collagen synthesis overall

Answer 27

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

Question 28

Diseases of defective collagen

Answer 28

Scurvy Inherited: Ehlers-Danlos Osteogenesis Imperfecta Alport syndrome

Question 29

Scurvy - why?

Answer 29

Vitamin C deficiency Unable to hydroxylate pre-procollagen Defective triple helix and defective collagen

Question 30

Scurvy symptoms/signs

Answer 30

Poor wound healing Bruising Bleeding of gums Tooth loss

Question 31

Ehlers Danlos syndrome

Answer 31

Collagen fibres lack tensile strength Poor wound healing Joint dislocation Hypermobile joints Rupture of colon/organs/arteries

Question 32

Skin Ehlers Danlos

Answer 32

Hyperextensible Fragile Suceptible to injury

Question 33

Osteogenesis imperfecta

Answer 33

Brittle bone disease Skeletal fragility - little bone tissue BLUE SCLERA - too little collagen so is not transparent Hearing impairment Dental abnormalities

Question 34

Alport syndrome

Answer 34

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)

Question 35

How is regenration controlled?

Answer 35

Direct cell contact Local mediators (growth factors) Hormones

Question 36

Cell to cell contact

Answer 36

Contact inhibition - isolated cells replicate until they encounter other cells Cadherins bind and prevent proliferation

Question 37

Cancer cell to cell contact

Answer 37

Cadherins are defective | Continued proliferation = multilayers

Question 38

Growth factors

Answer 38

Polypeptides that act on cell surface receptors | Cause cell to enter cell cycle —> proliferate

Question 39

Growth factor examples

Answer 39

Epidermal GF Vascular Endothelial GF Platelet derived GF Tumour necrosis factor

Question 40

Two types of skin healing

Answer 40

Primary intention | Secondary intention

Question 41

Primary intention

Answer 41

Apposed edges (near eachother/sutured) Minimal clot/granulation tissue = small scar Epidermis regenerates, dermis fibrous repairs

Question 42

Secondary intention healing

Answer 42

``` Unapposed edges (infection/ulcer/abcess) Significant tissue loss = lots of contraction needed ``` Abundant clot, inflammation, granulation tissue Dermis - repair Epidermis regenerates from edges

Question 43

Fracture healing stages

Answer 43

Haematoma (granulation) Soft callus (fibrous/cartilage) woven bone Hard callus (woven bone to lamellar bone) Remodelling (original outline)

Question 44

How long for soft and hard callous formation?

Answer 44

1 week soft | Several weeks hard

Question 45

How long for a fracture to be completely remodelled?

Answer 45

Months/years

Question 46

Local factors influencing wound healing

Answer 46

``` Size Location Blood supply Infection Foreign bodies ```

Question 47

Systemic factors influencing wound healing

Answer 47

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

Question 48

Complications of fibrous repair

Answer 48

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) ```

Question 49

When does insufficient fibrosis often occur?

Answer 49

Obese Elderly Malnutrition Steroid use