MEDSCI 201 - Human Structure and Function

study of histology

tissue level of organisation, cells and ECM components are the building blocks of tissue which control tissue function

connective tissue consists of

cells and extracellular matrix

extracellular matrix

a three-dimensional network consist of extracellular molecules and minerals: proteins (e.g collagen,elastin), glycoproteins, proteoglycans, minerals and hydroxyapatite that provide structural and biochemical support to surrounding cells and tissues

cells in connective tissue proper

fibrocytes

cells in cartilage

chondrocytes

ground substance

amorphous gel-like substance in extracellular space containing ECM components excluding fibrous, primarily composed of water and large organic molecules

Glycosaminoglycans

polysaccharides that trap water, giving ground substance the gel-like texture

glycoproteins and proteoglycans

modified proteins that have oligosaccharide (glycoprotein) or polysaccharide (proteoglycan) attachments, give ground substance structure and attach components of ground substance to each other and other cells

which fibres are long and branched, provide strength and can be flexible but are strong when pulled from either end?

collagen

which fibres are thinner and branched but consist of collagen forming a strong but flexible structure?

reticular

elastic fibres have the ability to stretch up to ?% of its length compared to collagen of 10%

150

areolar connective tissue holds organs in place by attaching epithelial to underlying tissues and provides ...

cushioning

areolar connective tissue allows cell movement which is access for the --- --- to respond to --- and ---

immune system, infection, injury

adipose tissue is made up of primarily adipocytes which is an --- ---

energy store

reticular connective tissue is found supporting which organs?

spleen, kidney, liver

loose connective tissue contains much more --- --- than dense connective tissue

ground substance

dense regular ct is collagen aligned in parallel providing firm attachment and strength helping to stabilise --- of ---

position of bones

dense irregular ct is made up of collagen fibre bundles, what is its primary function?

to resist forces from many different directions while providing strength

hyaline cartilage contains chondroitin sulphate proteoglycans that attach to polysaccharides which trap water allowing for tissue to undergo

compression (to a certain extent)

hyaline cartilage functions

reduce friction, allow for compression, provide flexible support

elastic cartilage is the ct that makes up the ear, what does this allow for?

the tissue is able to distort but return to its shape

fibrocartilage is found where? it resists compression to a much greater degree.

intervertebral discs

woven bone is formed during development and is mechanically weak, where else is it found?

in the centre of long bones allowing for production and presence of bone marrow and immune cells

the extracellular matrix of bone consists of

hydroxyapatite (crystals of calcium salt) and collagen

what connective tissue makes up tendons and ligaments?

dense regular ct

what connective tissue supports intestines and skin?

areolar ct and dense irregular ct

fascia is another term for

dense regular ct

intramembranous ossification occurs during

first 8 weeks of development, in utero

Mesoderm develops mesenchyme - embryonic mesenchyme cells + collagen, MSC's condense and develop into osteoblasts, deposit osteoid, osteocytes, bony spindles form and join together trapping blood vessels inside, bone is continued to be laid down in periphery, this process is called

intramembranous ossification

intramembranous ossification occurs where

in bones of clavicle, skull and mandible

zone of resting cartilage is

hyaline cartilage

what is the second stage in endochondral ossification?

simple hyaline cartilage framework

mesenchymal stromal cells are also

osteoprogenitor cells

osteoclasts are from what cell lineage?

white blood cell lineage

does all cartilage become bone in endochondral ossification?

no, some cartilage specialises as persistent cartilage

articular cartilage is found where?

at the ends of long bones and in synovial joints

Sox9 and Sox5/6 are transcription factors required in chondrogenesis for differentiation from

condensed prechondrocyte (chondroblast) to early chondrocyte

in endochondral ossification, when blood vessels begin to invade, the perichondrium begins developing cells into

osteoblasts

hypertrophic chondrocytes secrete calcified cartilage matrix which limits --- of ---, and chondrocytes die leaving empty ---

diffusion, nutrients, lacunae

zones from epiphysis to diaphysis tips: zone of resting cartilage -> proliferation -> --- -> --- -> bone deposition

hypertrophy, calcification

chondrocytes die leaving empty lacunae for

blood vessels to penetrate cartilage and invade

what migrates during skeletogenesis with invading blood vessels?

fibroblasts, which differentiate into osteoblasts

capillaries and osteoblasts migrate into the epiphyses, creating what?

secondary ossification centres

majority of bones (below neck) in body formed by process of

endochondral ossification

tissues designed to cope with mechanical force are

specialised connective tissue - bone, cartilage, tendons / ligaments

components that determine mechanical properties of tissue

collagen and proteoglycans

we (our tissues) are made up of

insoluble fibres (collagen) and soluble polymers (proteoglycans)

how many insoluble fibre collagens are discovered in humans so far

28

Type I collagen supports elements of high tensile strength, commonly found where?

bone, skin, tendons/ligaments

Type II collagen is found where?

cartilage, vitreous eye, intervertebral disc

Type III collagen is found in reticular fibres, and is commonly found in?

skin and blood vessels

Type IV collagen is mesh network found in basement membranes allowing for diffusion where?

in walls of blood vessels, blood cells and important in kidney

Type I collagen strength comes from?

tightness of coiling around central glycine

intracellular steps of collagen type I synthesis

1. Synthesis of pro-alpha chain containing Gly-X-Y repeats. -> (hydroxylation of proline and lysine) 2. Self-assembly of three pro-alpha chains. -> 3. Procollagen triple helix formation followed by secretion into the ECM.

extracellular steps of collagen type I synthesis

cleavage of propertied -> Self-assembly into fibril -> Aggregation of collagen fibrils to form a collagen fibre -> form fascicle

glycine, proline, lysine are secreted by the

rough ER

propeptides inhibit formation of

fibrils

small glycine allows for mechanical strength of collagen allowing

tight coil

what is vitamin C crucial for?

coiling collagen

Vitamin C is essential for the production of ----- -----, the enzyme that catalyses the hydroxylation of ---- and ----

lysyl hydroxylase, proline, lysine

where vitamin C is absent, collagen does not form the

essential coiled structure

scurvy is most prominent in areas with high rates of collagen turnover such as

periodontal ligament - holds teeth in place

how does osteogenesis imperfecta come about?

is a genetic disease, mutation in the two genes that encode collagen Type I

proteoglycans are ---- ---- that act as glue acting as hydrated gel to fill space

soluble polymers

proteoglycans are made up of

a core protein + one or more covalently attached glycosaminoglycan (GAG) chain(s)

GAG side chains are negatively charged due to what?

sulphate and uronic acid

What does the negatively charged GAG side chains of proteoglycans allow to occur?

pulls in positive cation, creating an ionic and osmotic gradient, pulling in water, allowing hydration

GAGs extend perpendicularly from core in ---- structure

brush-like

linkage of proteoglycans to GAG HA is by

link protein

linkage of GAGs to protein core involves specific trisaccharide composed of

two galactose residues and xylose residue

predominant proteoglycan in cartilage and intervertebral discs

aggrecan

predominant proteoglycan in bone and tendon

decorin

GAGs that aggrecan link to in cartilage and intervertebral discs are

chondroitin sulphate and keratin sulphate

where is the proteoglycan aggrecan abundant in intervertebral discs

centre nucleus pulposa

function of decorin

decorates collagen fibres, controls collagen diameter

high abundance of aggrecan in cartilage allows for

compression

the non-sulphated glycosaminoglycan

hyaluronic acid / hyaluronan

hyaluronic acid binds water which is important for

tissue hydration, joint lubrication and diffusion of molecules esp during development

aggrecan binds to ---- and is a larger aggregating protein rich in --- ----

hyaluronan, chondroitin sulphate

Loss of aggrecan in the intervertebral disc with age results in less ?

shock-absorbing capacity in centre nucleus pulposa

fibrillar collagens are broken down by enzymes termed ?

metalloproteases (MMPs)

what breaks down proteoglycans

ADAMTS

elastin / elastic molecule has multiple random coiled domains allowing for

expanding and contracting to allow network to stretch and recoil

in bone, water makes up 25%, minerals make up 60-70% resisting ---- whereas collagen makes up 5-10% resisting ----.

compression, tension

Collagen fibres (mainly type I) spiral along the length of each lamella (of bone) providing

excellent resistance to tensile forces

very little ----? present in bone

proteoglycan

corticol bone has ----- compressability than trabecular

20-fold

Strength of bone is dependent on

quality and amount of collagen (mainly type I);

mineral content (hydroxyapatite);

overall density

functionality of spongy bone

helps distribute loads, makes bone lighter and protects the marrow within

bone is highly adaptable, remodelling and repair occurs in response to

environmental stimuli of loading and unloading

which connective tissue adopts this characteristic: the more you load it the stronger it gets

bone

where there is increased osteoclast activity and reduced osteoblast activity you get the condition of?

osteoporosis

osteopenia

Lower than normal bone density and a precursor to osteoporosis.

calcium in bone - excess secreted and readily sourced for

signalling & cardiac function

for prevention of osteoporosis, most effective preventer is weight-bearing activity, such as walking and jogging subjecting bones to load, bone cells respond by

laying down more collagen and mineral salts in the bone matrix to make bone stronger

Articular cartilage is a specialised form of --- --- that is hard to repair & return to specialised state

hyaline cartilage

articular cartilage is found where?

at the end of bones within synovial joints - protect bone ends that come together (to form a joint)

composition of articular cartilage

water - 70-85%

collagen 10-20%

proteoglycans 5-10%

chondrocytes 5%

is aneural & avascular

cells maintain themselves on anaerobic metabolism in which connective tissue?

articular cartilage

proteoglycan monomer (aggrecan) linked to hyaluronic acid molecule by link protein in cartilage, hyaluronic acid molecules form linear aggregates, each with many proteoglycan monomers attached/linked, which are interwoven within a

network of collagen type II fibres