3 - Peritoneal Pathologies

Question 1

What are the two types of peritoneum?

Answer 1

Parietal

Visceral

Question 2

What is the name of a double-fold of peritoneum?

Answer 2

Mesentery

Question 3

What 3 layers make up the peritoneum?

Answer 3

Mesothelium
Basement membrane
Submesothelial layer

Question 4

From what tissue is the mesothelium derived from?

Answer 4

Mesoderm

Question 5

What structure increases the SA of the mesothelium?

Answer 5

Microvilli

Question 6

What is the peritoneum bathed in?

Answer 6

Peritoneal fluid

Question 7

What are the 3 functions of the peritoneum?

Answer 7

1) Non-adhesive barrier (role of surfactant)
2) Solute / fluid transport
3) Immune function

Question 8

How does the mesothelium provide an immune function?

Answer 8

Mesothelial cells can act as APC cells

Can also produce cytokines too.

Question 9

What are 3 peritoneal pathologies ?

Answer 9

Adhesions

Endometriosis

Encapsulated peritoneal sclerosis (Long-term PD)

Question 10

When do peritoneal adhesions form?

Answer 10

After peritoneal injury (surgery)

Question 11

What are the 2 most common complications of adhesion formation?

Answer 11

1) Small bowel obstruction (most common cause)

2) Infertility in women (fallopian tube obstruction) - 1/3 of all cases

Question 12

How much do adhesions cost the NHS?

Answer 12

£56 million a year

Question 13

What are the only treatments currently to prevent adhesion formation?

Answer 13

Physical barriers to hold organs apart.

e.g. gels

Question 14

What are 4 processes that occur for adhesions to form?

Answer 14

Inflammation
Blood vessel ingrowth
Collagen deposition
Contraction

Question 15

What two differences seperate scar tissue from healthy tissue?

Answer 15

Scar tissue is:

1) Avascular
2) Acellular

Question 16

What two findings resulted in the conclusion that adhesions were dissimilar to scar tissue?

Answer 16

Adhesions are well vascularised.

Adhesions contain nerves.

Question 17

What stimuli were the nerves in adhesions capable of sensing?

What did they express?

Answer 17

Pain.

Substance P.

Question 18

What 2 proteins are capable of cleaving plasminogen into plasmin?

Answer 18

uPA (plasminogen activator urokinase)

tPA

Question 19

Which of the two cleavage proteins was shown to be the most important in adhesion formation?

Answer 19

tPA

Question 20

What is the role of plasmin?

Answer 20

Breakdown of fibrin clots.

Question 21

What is the half life of tPA?

Answer 21

30 seconds

Question 22

What are the 3 functions of TGF-beta?

Answer 22

1) Wound healing
2) Tissue repair
3) Growth and development

Question 23

How many types of TGF-Beta are there? What are they called?

Answer 23

3.

TGF-Beta 1/2/3

Question 24

What is TGF-beta’s effect on collagen production in wound healing process?

How does it do it?

Answer 24

Increases expression of PAI-1.

Increases collagen production.

Question 25

What two receptors does TGF-Beta signal through?

Answer 25

TGF-Beta Receptor I / II

Question 26

What is the modulatory regulator of TGF-beta function / expression?

Answer 26

Its own receptor.

Question 27

Of the 3 TGF-Betas, what is the function of 1 and 2 compared to TGF-B3 in THE SKIN?

Answer 27

TGF-B 1/2 = scar formation TGF-B 3 = anti-scar formation

Question 28

What is the issue with placing medical therapy in the peritoneal cavity?

Answer 28

It does stay long enough! Also need a transport vehicle.

Question 29

What are the effects of TGF-B 1/2/3 in the peritoneum?

Answer 29

Scar formation!!

Question 30

What is the omentum?

Answer 30

A fatty peritoneal fold.

Question 31

What is the name of the 2 omenta in the body?

Answer 31

Greater | Lesser

Question 32

What characteristic does the omentum have when there's abdominal trauma?

Answer 32

Rapidly adheres to injured tissue.

Question 33

What reasons (2) does the omentum easily adhere to damaged areas?

Answer 33

High levels of: - Angiogenic factors - Neurogenic factors

Question 34

What was noticed on electron microscopy that may explain the omentum's tendancy to stick to trauma / clots ?

Answer 34

Fenestrations which may function like a sponge - sucking up the clot.

Question 35

How many women does endometriosis affect in the UK?

Answer 35

1.5 million

Question 36

What symptoms occur in endometriosis?

Answer 36

Pain Fatigue Infertility

Question 37

What feature about menses can result in endometriosis?

Answer 37

Retrograde flow of menstrual effluent.

Question 38

Where endometriotic tissue bleeds, what can form?

Answer 38

Adhesion formation (due to presence of fibrin clot)

Question 39

Despite retrograde menstrual effluent occurring in ALL women, what 3 areas have been thought to potentially be linked to endometriosis occurring in some and not others?

Answer 39

1) Extended viability of endometrial tissue 2) Varied peritoneal attachment 3) Varied scope of invasion / growth

Question 40

What two options could extend viability of endometrial tissue ?

Answer 40

Reduced apoptosis Abnormal immune response

Question 41

What 2 options may explain variance in ease of peritoneal attachment in endometriosis?

Answer 41

Peritoneal status | Altered ECM deposition

Question 42

Through GFP labelling, what was shown (Cross-talk) between implanted endometrial tissue onto peritoneum?

Answer 42

Cross-talk occurs. Endometrial tissue: 1) Spreads across peritoneum 2) Grows deep into peritoneum

Question 43

What is the cause / biggest risk factor for developing encapsulating peritoneal sclerosis?

Answer 43

Duration of PD

Question 44

How do encapsulating peritoneal sclerosis patients present?

Answer 44

Malnutrition | Bowel obstruction

Question 45

What is the management for EPS?

Answer 45

Surgery | + steroids

Question 46

What is the overall indication for dialysis?

Answer 46

End-stage renal disease

Question 47

What % of ESRD patients opt for PD and what % opt for haemodialysis?

Answer 47

85%

Question 48

What's the progression of peritoneal fibrosis in PD Patients?

Answer 48

High glucose, low pH dialysate. Creates glucose degradation products / advanced glycated products which damage peritoneum. Constant injury / repair cycle, resulting in peritoneal fibrosis.

Question 49

What growth factor is known to be released in the pathogenesis of EPS?

Answer 49

TGF-B1 | involved directly in collagen deposition / scarring

Question 50

What is the main cellular process that results in the thickening of the peritoneum, resulting in peritoneal dialysis?

Answer 50

Mesothelial-to-mesenchymal transition (MMT)

Question 51

What is the phenotype exchange that occurs in mesothelial-to-mesenchymal transition?

Answer 51

Epithelial --> mesenchymal.

Question 52

What characteristics do the epithelial phenotype of mesothelial cells (normal) include?

Answer 52

Lubricant secretion | Barrier function etc

Question 53

What is the pathophysiological changes that enable this phenotype change?

Answer 53

Loss of junctions / basement membranes.. Cells begin expressing mesenchymal markers. Increase ECM deposition. = fibrosis.

Question 54

What is one of the main stimulators of this transitional process?

Answer 54

TGF-Beta

Question 55

Developmentally, MMT is really important for the development of which structures?

Answer 55

Heart, lungs and gut vasculature.

Question 56

Adult MMT results in what?

Answer 56

Peritoneal thickening | Excessive matrix deposition

Question 57

Despite peritoneal sclerosis occurring following long-term PD. Why do only some people get encapsulating peritoneal sclerosis? What is the proposed hypothesis?

Answer 57

2-hit hypothesis: 1) First hit is the MMT process following peritoneal injury. 2) Calcium levels? Genetic predisposition?