Elastic fibres

DR RANJAN JEEVANNAVAR

Introduction

• Elastic fibre system is an integral component of

connective tissue and forms a network that is

responsible for resilience and elasticity of various

organs.

• Its required for proper structure and function of

cardiovascular, pulmonary, intestinal system.

• In normal individuals, elastic fibres form 3% of

total dry weight of dermis.

• Elastic fibres stores the energy during stretch

and drives the elastic recoil.

• Elastic fibres mainly composed of inner core of

amorphous elastin and outer electron dense

microfibrils .

Development

• First elements of elastic fibres that form consists

of bundles of microfibrils seen during the first

trimester .

• The alignment of these microfibrils are parallel so

as to accommodate elastin and grow uniformly.

• During second trimester, fibres remain immature

and branching in the fibres is seen.

Development cont.• Initially elastic fibres show masses of peripheral

microfibrils surrounding a small amorphous

electro lucent core i.e. elastin with only few

internal microfibrils .

• As the fetus matures the amount of elastin and

the number of microfibrils within the core

increases whereas the number of peripheral

microfibrils decreases.

• At 32 weeks a well developed network of

elastic fibres is present in both papillary and

reticular dermis .

Elastin

• It’s a highly cross-linked amorphous insoluble

protein which forms the core of mature elastic

fibres.

• Its constitutes 85% of mature elastic fibres .

• It is synthesised by smooth muscle cells in arteries

and intestine similarly fibroblasts in the skin.

• Elastin is initially sythesized as a precursor

polypeptide Tropoelastin.

• It consists of 700 amino acids with a molecular

mass of 70kDa.

• It is rich in glycine (33%), proline (10%) and

hydrophobic amino acids , alternating with

lysine and alanine rich sequences.

• Characteristic sequence is two lysine residues separated

by three alanine residues.

• The lysine residues in tropoelastin are critical for the

formation of covalent cross links and desmosines that

are unique to elastin.

• First oxidative deamination of three lysine residues to

form its corresponding aldehydes i.e. allysines and these

join with another lysine to form a stable desmosine

compound which covalently links two tropoelastin

polypeptides.

• Tropoelastin is secreted by elastin binding

protein and crosslinked on the surface of

fibroblasts by copper dependent enzyme lysyl

oxidase.

• Hence copper deficiency , wilsons syndrome ,

menkes syndrome associated with reduced

elastin.

• Additional elastin is added to aggregates

which are then linked to microfibrils that bind

to cell surface via integrins.

• Aggregation of elastin and microfibrils develop

into larger structures to form the functional

elastic fibres.

Elastin gene• Elastin gene is localized to chromosome 7q11

and regulates the synthesis of tropoelastin molecule.

• The hydrophobic and cross-link domains of the elastin protein are encoded in separate exons .

• The mRNA of elastin undergoes extensive alternate splicing so that the arrangement of exons coding for cross-linking domains keep changing with respect to hydrophobic region.

• Hence elastin molecules of varying primary

sequence is found.

• Significance of the variation not yet known.

• The defect in this gene leads to autosomal

dominant form of cutis laxa.

Microfibrils

• Its electron dense tubular fibrils of insoluble glycoprotein

complexes measuring about 10 to 12 nm in diameter.

• It regulates assembly and organization of elastic fibres.

• It has an outer electron dense shell surrounding an inner

lucid core and appears as a beaded chain.

• It consists of several distinct proteins like fibrillin 1 and 2,

fibulin 1,2,3,4,5 , associated microfibril protein, and elastin

receptor.

• Even lysyl oxidase enzyme is found to be a

part of microfibril core.

• The largest and the most important of these is

fibrillin, a 350kDa glycoprotein forming the

integral part of microfibril structure.

• Multiple fibrillin molecules align in parallel and

head to tail fashion to form elongated tubular

structure.

• Fibrillin 1 gene on chromosome 15q and mutation of this is found

to cause Marfans syndrome. Fibrillin 2 gene is in chromosome 5q

and its mutation causes contractural Arachnodactyly.

• Fibulins is essential for elastic fibre formation and assembly and

facilitates cell-matrix interactions. Mutations in its gene is found

in inherited cutis laxa.

• Associated microfibril protein is rich in acidic amino acids like

glutamic and aspartic acid and this helps in assembly of

tropoelastin molecules with its basic amino acid content.

Degradation

• The metabolic turn over of elastic fibres is slow.

These are degraded by elastases classically found

in pancreatic sectretions and others are matrix

metalloproteinases , proteinase 3.

• In skin, serine elastases from monocyte –

macrophages involved with elastic fibre turn over.

• Elastase inhibitors like α1-antitrypsin , α2-

macroglobulin and lysozyme are found in body.

• Any alteration in these will lead to increased

elastic fibre degradation as seen in

emphysema.

Factors affecting elastic fibre turn over

• Elastin production is increased by– Insulin like growth factor 1– Growth hormone– Epinephrine

• Elastin production reduced by– Tumour necrosis factor α– Transforming growth factor β– Interleukin 1– Vitamin D3

Types • Elastic fibres are of two types mainly– Oxytalan fibres – Elaunin fibres

• Oxytalan fibres contains microfibrillary component with no elastin, it emerges from the basement membrane of stratum basale in a perpendicular orientation and goes deep into papillary dermis where it merges with elaunin fibres.

• Elaunin fibres : contains microfibrils with

small amount of elastin core forms a plexus

parallel to dermo-epidermal junction in

papillary dermis.

• A dense network of elastic fibres is found in

the matrix of reticular dermis which primarily

consists of elastin and very little microfibrils.

Sites

• Walls of arteries, veins , intestine, skin , elastic

cartilage, bronchioles etc.

• The highest concentration of elastic fibres

seen in aorta and to some extent in papillary

and reticular dermis of skin.

Elastic property

• Hydrophobic segments of elastin is found in a loose

water containing helicals of β- spirals.

• Multiple random spirals are present in the entire

polypeptide chain of elastin.

• Upon stretching, the spirals distance with each other

and the hydrophobic forces drives the recoils of the

chain.

Functions

• Cardiovascular system : During systole the

work of the heart is absorbed by expansion of

the great vessels mainly aorta which is rich in

elastic tissue which then elastically recoil

during diastole maintaining the blood pressure

assuring continuous perfusion of the tissues .

• Respiratory system: inspiration is an active

energy consuming process, and the expiration

occurs passively due to the elastic recoil of the

respiratory tree.

• Intestines : the coils dilates when the food

comes into the segment and with peristalsis

pushing the food forwards, the elastic recoil of

the intestine brings back to original shape.

• In skin elastic fibres are responsible for – Tension : the resistance of the skin to deforming

forces – Elasticity : ability of skin to resume to its original

shape after deforming forces. This is reduced in cutis laxa and aged .

– Tensile strength : the degree to which skin can be elongated before it tears .

• These properties helps the skin to adapt to local changes in body size and contour, to allow movements of head and limbs and a wide range of facial expressions.

Histology• Elastic fibres are not visible in routine stains.

• Special stains required to demonstrate these fibres

are

– Verhoeff-van Gieson Stain : black colour

– Gomori’s aldehyde fuchsin stain : blue-black color

– Orcein stain : red-brown color

– Weigert’s stain: purple-violet color

– Luna stain : briliant purple

Elastic fibres are interspread among the

collagen fibres in dermis

Age related changes

• After age of 50 the fibres are loosely arranged.• Elastic fibres fragments and develop granular,

indistinct borders.• The microfibrillary component goes on

reducing and increase in elastin portion.• There is considerable decrease in number of

elastic fibres in papillary dermis and increase in reticular dermis.

Elastic fibre disorders

• Cutis laxa : fragmentation and loss of elastic fibres• Pseudoxanthoma elasticum : progressive

calcifictaion and fragmentation of elastic fibres.• Wrinkly skin syndrome : decreased number and

length of elastic fibres.• Anetoderma : localized loss of elastic fibres in

dermis • Mid dermal elastolysis : loss of elastin in mid

dermis

• Post-inflammatory elastolysis : localised loss of

elastic tissue secondary to insect bites.

• Marfans syndrome : mutation in fibrillin 1 gene

with abnormal microfibrils.

• Actinic elastosis : accumulation of irregularly

thickened elastic fibres on long term sun exposure.

• Elastoderma : accumulation of excessive and

deranged elastin

References • Rooks text book of dermatology 8th edition• Fitzpatricks dermatology 7th edition• Levers histopathology of skin 10th edition• Weedons histopathology of skin• Robins textbook of pathology• Bolognia 2nd edition• Moschella 3rd edition• Rosenbloom J , Abrams WR. Extracellular

matrix 4 : The elastic fibre