PBL 5

Question 1

Haematoma

Answer 1

an abnormal collection of blood that has clotted outside a blood vessel

Question 2

Subcutaneous nodule

Answer 2

a firm lump under the skin that is often the result of infection and inflammation

Question 3

Hyper-extensible

Answer 3

being able to be stretched to a greater than normal degree

Question 4

Episiotomy

Answer 4

a surgical cut made in the perineum to enlarge the vaginal opening for childbirth

Question 5

Skin biopsy

Answer 5

a small sample of skin is removed and examined under an electron microscope

Question 6

Name some autosomal dominant diseases

Answer 6

• huntingtons,
• marfans syndrome
• classic elhers danlos

Question 7

Name some autosomal recessive

Answer 7

cystic fibrosis and sickle cell

Question 8

name some X linked dominant

Answer 8

Fragile X syndrome

Question 9

Name some X linked recessive

Answer 9

haemophilia

Question 10

if one parent has elhers danlos then …

Answer 10

50% chance that the child will get it

Question 11

how many people does EDS effect

Answer 11

1 in 5000

Question 12

how many different types of EDS are there

Answer 12

10 different types which are classified in 6 major groups

Question 13

What is ehlers-danlos syndrome

Answer 13

A heterogenous group of inherited connective tissue disorders.

Question 14

who does Ehlers danlos effect

Answer 14

• caucasians more than other races

- usually manifests in young adults as some of the clinical manifestations only develop during early childhood

Question 15

How is elhers dakloos mis diagnose

Answer 15

• only 5% of suffers receive a diagnosis

Question 16

what is each type of EDS charactersticed by

Answer 16

• Gene mutation

- inheritance patterna dn symptom

Question 17

describe the genetics and clinical manifestation of EDS classic (type 1 and type II)

Answer 17

• COL5A1
• COL 5A2
• TYPE V COLLAGEN
• autosomal dominant
  2nd most prevalent type after hyper mobility
• can arise from de novo - caused by a mutation in a germ cell and occurs in many cases

Question 18

how many individuals does classic EDS occur in

Answer 18

1 in 20,000

Question 19

what collagen does classic EDS affect

Answer 19

• affect type V collagen

type I - severe skin involvement
type II - mild to moderate skin involvement

Question 20

What are the clinical features of classic EDS

Answer 20

Skin hyper-elasticity
Atrophic scars
Joint hypermobility
Abnormal bleeding
Bruising
Fragile tissue

Question 21

what do COL5A1 and COL5A2 code for

Answer 21

code for collagen type V

Question 22

what does collagen type V do

Answer 22

Collagen V regulates fibril formation and co-polymerization of collagen type I.
- regulates the dimatere and assembly of heterotypic type I collagen fibres

Question 23

describe how collagen V affects collagen I

Answer 23

In classic EDS, abnormal collagen V production affects collagen I.
Collagen I makes up the majority of collagen in the dermis and a large proportion in cartilage, so EDS indirectly affects this.

Question 24

How does collagen type V form

Answer 24

Synthesis of type V collagen begins with three pro-α(V) chains wound around each other to form a triple helix. There are two types of pro-α(V) chains: pro-α1(V) is coded for by the COL5A1 gene, whilst pro-α2(V) is coded for by the COL5A2 gene. Type V collagen can be composed of three pro-α1(V) chains or two pro-α1(V) and one pro-α2(V) chains.
These triple-stranded procollagen chains are secreted from the cell and processed by enzymes to from mature type V collagen which copolymerises with type I collagen
- short fibril intermediates are formed which increase in size through linear and lateral fusion events

Question 25

when does growth of collagen type V stop

Answer 25

Fibril growth is stopped by type V collagen when the diameter of the type I collagen fibrils becomes consistent.

Question 26

what happens in the absence of collagen V

Answer 26

- results in unregulated collagen I assembly - absence of or insufficient type V collagen results in unregulated self assembly of type I collagen fibrils which causes irregularities their diameter and shape

Question 27

what is the mutation in Andreas' case

Answer 27

- C → G in the COL5A1 gene caused a nonsense mutation. - Truncated COL5A1 mRNA disrupted collagen V formation. - Non-functional collagen V caused collagen I fibrils to become irregular and disordered. - Tight packing of collagen I disrupted = Characteristic abnormalities of classic EDS.

Question 28

what are major criteria of classic EDS

Answer 28

- skin hyper extensibility - widened atrophic scarring - joint hyper mobility - positive family history

Question 29

what are minor criteria

Answer 29

- smooth velvety skin - subcutaneous spheroids - easily bruising - manifestation of tissue extensibility and fragility

Question 30

How do you diagnose EDS

Answer 30

Physical examination - look for clinical features Assess hypermobility using Beighton criteria Major criteria includes arthralgia (joint pain > 3 months) and 5/9 Beighton score) Skin biopsy for collagen typing Collagen gene mutation testing

Question 31

What does a physical examination involve

Answer 31

- involves testing the skin if the skin feels fragile, soft and velvety - hyper extensibility can be tested by pulling the skin and seeing how quickly it returns to its original state after release - EDS has skin that will extend and immediately snap back - Beighton score to identify the extent of a patients joint hyper mobility - family history

Question 32

How do you test for EDS

Answer 32

- genetic test - determine the base sequence of either COL5A1 or COL5A2 by Sanger sequencing 0 classic EDS will possess a premature stop codon in one of these genes - skin biopsy - allows analysis of collagen fibres using gel electrophoresis, abnormal collagen proteins in patients with EDS will migrate in a visibly different way on the gel compared to collagen proteins

Question 33

How to treat EDS

Answer 33

``` No specific treatment Measures should be taken to manage symptoms and prevent further damage to skin & joints Physiotherapy Painkillers Vitamin C - reduce bruising Avoid contact sports ```

Question 34

what does the epidermis contain and what cells is it made out of

Answer 34

- in stratified squamous epithelium - contains keratinocytes that produce keratin - also contains melanocytes and langerhnas cells

Question 35

what are the layers of the skin

Answer 35

``` Stratum corneum (C) – corny Stratum lucidum (L) - lucy Stratum granulosom (G) –gets Stratum spinosum (S) – super Stratum basale (B) - baked ``` Dermis

Question 36

what are the 3 main layers of the skin

Answer 36

- epidermis - is stratified squamous epithelium that is made up of mainly keratinocytes - dermis - This layer of skin contains hair follicles and sweat glands, embedded in dense irregular connective tissue (which is made up of collagen and elastic fibres). Fibroblasts and immune cells are abundant in the dermis - hypodermis - The hypodermis (also called subcutaneous tissue) forms the lower layer of the skin. It contains blood vessels and adipocytes, which store lipids for energy release.

Question 37

what separates the epidermis and dermis

Answer 37

basement membrane

Question 38

How does wound healing take place

Answer 38

1. Haemostasis - Forming stable clot - enzyme thrombin converts fibrinogen to fibrin, allowing the formation of a fibrin clot at the site of infection 2. Inflammation - High blood supply, release of cytokines and growth factors - neutrophils and macrophages migrate to the wound and stimulate inflammation 3. Proliferation - Increased fibroblasts, which begin to lay down new extracellular matrix, including collagen. - fibroblasts multiply and secrete collagen fibres into the extracellular matrix 4. Re-modeling - Completion of ECM deposition, healing of epidermis - where collagen fibres become organised to form the new, mature tissue

Question 39

what part of wound healing is affected by EDS

Answer 39

Stage 4 is effected by EDS: In normal wound healing, collagen III is deposited largely at first then replaced by collagen I. This does not occur properly in EDS This has an effect on wound contraction, meaning wounds gape and are atrophic. . It is this stage that is affected by EDS as the collagen fibres cannot organise themselves into regular structures. Only partial wound contraction occurs, leading to scars that gradually widen.

Question 40

what is child abuse

Answer 40

Child abuse = When a parent or caregiver, whether through action or failing to act, causes injury, death, emotional harm or serious risk to a child. Includes neglect.

Question 41

what are the most common concerns of child abuse

Answer 41

Emotional abuse Neglect Parental substance abuse