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what is a tissue?
a collection of specialised cells that perform a particular function
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list types of biopsy
- smear
- curettage
- needle
- endoscopic
- transvascular
- direct incision
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how are tissues fixed?
glutaraldehyde/formaldehyde
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why are tissues fixed?
maintains structure during handling and make cell parts visible
processing can lead to shrinkage artefacts
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describe Hand E stain
- H=haematoxylin - a basic dye stains nuclei blue
- E = eosin - stains cytoplasm pink
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what is the staining from the Periodic Acid Schiff reaction?
- blue nuclei
- pink collagen fibres
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name different types of microscopy and their uses
- phase contrast - used to study cell cycle as not in a vacuum and doesn't require staining
- dark field - used for smears as it improves contrast of transparent unstained specimens
- fluorescence - early diagnosis of TB and meningitis
- confocal - used to build 3D images
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what is the limit of resolution?
the minimum distance at which two points can be distinguished - electron microscopes have finer resolutions as electrons have a smaller wavelength than light
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what is the difference between heterochromatin and euchromatin?
- heterochromatin - DNA not in active synthesis
- euchromatin - active in RNA synthesis
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what is an epithelium?
sheet of contiguous cells of varied embryonic origin that cover the external surfaces of the body and line the internal surface
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what are the 4 classifications of tissue?
- muscle
- nervous
- connective
- epithelial
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how are epithelial cells classified?
- simple squamous - lining heart and blood vessels (endothelium), pleural and peritoneal cavities (mesothelium), and epithelium
- stratified squamous - found in oral cavity, vagina and oesophagus, can be keritanised - the skin
- simple cuboidal - line ducts of exocrine glands - kidney tubules and thyriod
- simple columnar - secretion of enzymes and mucus line the GI tract and large excretory ducts of glands
- pseudostratified ciliated - respiratory epithelia, upper resp tract, ear, nose.
- transitional - allows for distension and protection - bladder and ureter
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regeneration of epithelial cells - rates?
they have the capacity to regenerate - eg. wound healing, replacement of skin, GI lining, uterine after menstruation
metaplasia - changing type - eg. resp epi - stratified squamous in heavy smokers
neoplasia - form carcinomas
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where are mucous membranes found?
- lining the surfaces of open cavities
- the GIT, resp tract, reproductive and urinary tract
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what are the typical 4 layer of a mucous membrane (mucosa)?
- epithelium
- basement membrane
- lamina (tunica) propria
- muscularis mucosa
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lining of GIT?
- mucosa/mucous membrane - contains glands in SI
- submucosa - dense irregular CT with large vessels and nerves
- muscularis externae/ muscularis propria - inner circular and outer longitudinal layer - peristalsis
- serosa/adventitia
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lining of the urinary tract?
- ureters urinary bladder and urethra transitional epi
- lamina propria - fibroelastic
- muscularis externae is thick
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what is a gland?
an epithelial cell or an aggregation of epithelial cells specialised for secretion
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what is the difference between endocrine and exocrine?
- endocrine secretion is straight in to the blood stream
- exocrine glands have ducts
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divisions of exocrine glands?
- by STRUCTURE -
- - unicellular/multicellular
- - simple tubular/simple branched/simple coiled/simple acinar/simple branched acinar/ compound tubular/compound acinar
- by NATURE OF SECRETION -
- - mucus - high in mucins stain poorly with H&E
- - serous - high in enzymes, watery - stain pink with H&E
- by METHOD OF SECRETION -
- - merocrine - exocytosis
- - apocrine - non membrane bound structure ends up outside cell in a droplet
- - holocrine - disintergration of whole cell releases all contents this happens with sebaceous glands cells
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what is transepithelial transport?
coupled endo and exocytosis
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what is the function of the golgi?
packing, concentrating and modifying proteins from the RER
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What is the purpose of glycosylation?
allows specificity by offering complex shapes
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how is secretion controlled?
- nervous
- endocrine
- neuro-endocrine
- negative feedback
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examples of exocrine glands
- goblet cells in jejunum, colon
- salivary glands
- pancreas - enzyme part
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examples of endocrine glands?
- thyroid
- parathyroid - chief cells secrete PTH
- adrenal gland
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layers of adrenal gland
- MEDULLA
- - NA and A
- CORTEX
- - zona reticularis - androgens
- - zona fasiculata - glucocorticoids - cortisol
- - zona glomerulosa - mineralocorticoids - aldosterone
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what is connective tissue?
- mostly derived from mesoderm
- functions = support, defence, transport, repair
- mainly extracellular components with few cells
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categories of connective tissue?
- embryonic - mesenchymal, mucous
- adult - loose, relicular, adipose, dense irregular, dense regular (collagenous/elastic)
- specialised - supporting (bone/cartilage), blood
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describe embryonic mesenchymal connective tissue?
- cells - mesenchymal cells
- extracellular - fine reticular fibres (thin branching carbohydrate coated type III collagen) and small blood vessels
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describe embryonic mucous connective tissue
where is it found?
- cells = fibroblasts
- extracellular = irregular collagen bundles
found deep to fetal skin and in the umbilical cord
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describe adult loose/areolar connective tissue
where is it found?
- cells = fibroblasts, macrophages, plasma cells, mast cells, adipocytes
- extracellular = slender long collagen bundles, elastic fibres, reticular fibres, ground substance
ground substance is composed of GACs, proteoglycans and glycoproteins it forms a matrix for cell adhesion
found in superficial fascia/subcutaneous tissue, organs, between fasicles...
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describe adult reticular connective tissue
where is it found?
- cells = reticular cells, lymphocytes and macrophages
- extracellular = reticular fibres
classic lymph tissue - lymph nodes
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describe adult adipose tissue
where is it found?
cells = closely packed adipocytes separated by thin sheets of extracellular reticular and collagen fibres
subcutaneous fat
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describe dense irregular connective tissue
where is it found?
- cells = fibroblasts, macrophages
- extracellular = haphazard, thick, wavy collagen bundles and some reticular and elastic fibres
dermis, deep fascia, periosteum
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describe dense regular collagenous connective tissue
where is it found?
- cells = parallel (few) rows of flattened fibroblasts
- extracellular = densely packed regularly arranged collagen fibres
tendons, aperneurosis
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describe dense regular elastic connective tissue
where is it found?
- cells = rows of flattened fibroblasts
- extracellular = bundles of thick elastic fibres - made from elastin
found in the lungs
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what is marfans?
- genetic defect on chromosome 15
- underdevelopment of elastic fibres
- heart/blood vessels/eyes/skeleton
- long fingers...
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what is Ehlers-Danlos syndrome?
- collagen abnormality > joint dislocations and hyperextensibility
- autosomal dominant inheritance
- dissecting aortic aneurysm at an early age
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main structure of the skin
- main layers
- epidermis
- epidermal basement membrane
- dermis
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describe the structure of the epidermis
- epidermis has 4 layers -
- - stratum corneum - stacks of dead cells called squames key function = protection
- - the granular layer - contains keratohyalin granules and other fibrous proteins which degrade the phospholipid membrane and xlink proteins - this is where the keratinocytes lose their membrane and become cells of the stratum corneum
- - the prickle cell layer - daughter keratinocytes terminally differentiate and lose the ability to divide
- - the basal layer - keratinocyte mitosis
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how long does it take for a keratinocyte to go from the basal layer to the stratum corneum
30 - 40 days
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name two cells other than keratinocytes in the epidermis and their role
- melanocytes are dendritic cells of neural crest origin they occur at intervals along the basal layer and produce melanin in darker skin there are the same amount they are just more active
- langerhans cells are dendritic cells of bone marrow origin they are scattered through the prickle layer and are designed to present antigens to Tcells mediating the immune response
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describe the structure of the dermis
- tough, fibrous, vascular layer, fibroblasts synthesis the
- extracellular matrix which contains collagens and elastin.
- The other main components = blood and lymph
- vessels. mast cells and nerves
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list some skin appendages
- hair follicles
- sebacous gland
- nails
- sweat glands
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list the main functions of the skin
- protection
- barrier
- sensation
- thermoregulation
- sociosexual communication
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list some diseases of the skin
- leprosy
- diabetic sensory neuropathy
- psorasis
- hyperhidrosis
- acne
- alopecia areata
- keloids
- vitiligo
- allergic contact dermatitis
- basal cell carcinoma/malignant melanoma
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where is cartilage found?
- fetal skeleton
- costal cartilages
- articulating surfaces of bone
- C-rings of the trachea
- pubic symphsis
- ...
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what are the three types of cartilage?
- hyaline
- elastic
- fibrocartilage
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describe hyaline cartilage
- most common
- can ossify in old age and disease
- makes up fetal skeleton remains in adult as costal cartilages, thyroid cartilage, articular cartilage, C rings of the trachea
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describe elastic cartilage
- matrix is rich in collagen and elastin fibres
- doesn't calcify or ossify with age
- found in the ear canal and epiglottis
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describe fibrocartilage
- irregular dense fibrous tissue with few chondrocytes
- found in symphsis, intervertebral discs, articular discs in the knee joint and the sternoclavicular joint
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describe the structure of cartilage
- avascular
- strong somewhat pliable
- firm proteoglycan matrix
- the cells are chondrocytes they form chondroblasts which secrete matrix trapping the cell in lacunae - they are then called chondrocytes
- most cartilage (NOT fibrocartilage) is surrounded by a dense irregular connective tissue called perichondrium which vasularises the cartilage by diffusion
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how does cartilage grow?
- INTERSTITIAL GROWTH - chondrocytes divide within lacunae to form isogenous groups
- APPOSITIONAL GROWTH - is adding new cells to the surface but requires undifferentiated cells
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can cartilage repair?
- little capacity to repair
- fibrous/scar tissue is laid down by the perichondrium
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what is the make up of the bone matrix?
- 65% inorganic - calcium phosphate etc.
- 35% organic - mostly collagen
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what are the types of bone?
- compact/dense/cortical
- spongy/cancellous/trabecular/medullary
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what is the difference between spongy and compact bone?
- spongy bone has large open cavities surrounded by plates of bone
- compact bone is harder it has smaller cavities and thicker lamellar
- spongy bone contains bone marrow
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describe the structure of bone
- bone is always covered and lined by soft connective tissues
- the marrow cavity is lined by endosteum
- the periosteum covering the bone has an outer fibrous layer of collagen fibres and fibroblasts and an inner osteogenic layer consisting of an osteoprogenitor layer and osteoblasts
- the periosteum is fixed to the bone by sharpeys fibres and damage/trauma to the periosteum is very painful
- bone matrix is formed by osteoblasts which are derived from osteoprogenitor cells as they lay down the matrix they become trapped in lacunae and are referred to as osteocytes.
- osteocytes have long processes which are housed in canaliculi which are tunnels that lead to haversian canals which contain blood vessels
- the osteocytes that join one haversian canal to another are known as osteons
- haversian canals are joined to each other by volkmann's canals
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how does bone remodel after a fracture?
- bone is continuously being remodelled - osteoclasts break it down and osteoblasts rebuild it.
- 1. haematoma - fibrin clot and bone fragments
- 2. procallus - inflammatory cell influx debris cleared
- 3. callus - fibrocartilage
- 4. healing - osteoprogenitor cells from periosteum lay down sleeve of bone - starts as spongy bone
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how is bone made?
bone forms from pre-existing tissue which is replaced
- there are two types of ossification:
- - intramembranous - bone development begins in highly vascularised CT, it begins at the primary centre of ossification and osteoblasts lay down osteoid - a non calcified matrix which later becomes calcified, the osteoblasts then become osteocytes.
- - cartilage is replaced, the primary centre is the diaphysis/shaft the secondary centres (the epiphyseal growth plates) occur at the epiphysis
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give an example of where intramembranous ossification occurs
flat bones of the skull
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give an example of endochondrial ossification
long bones
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what is achondroplasia?
congential and often hereditary shortness of limbs - thin epiphyseal growth plates
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what is osteogenesis imperfecta?
- brittle bones
- abnormal collagen synthesis
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what hormones affect growth?
- low growth hormone - pituitary dwarfism
- high growth hormone - gigantism/acromegaly(inc. in diameter)
- sex hormone deficiencies - epiphyseal growth plates don't close - tall stature
- thyroid hormone deficiency - cretinism
- high PTH - decalcification > inc. # risk
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how long do blood cells survive?
- RBCs - 120 days
- platelets - 10 days
- neutrophils - 2-4days
- lymphocytes - 1 day - years
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what is haemopoesis?
progentitor stem cells in the bone marrow differentiate into myeloidblasts which are precursors for erythrocytes, granulocytes, monocytes and platelets. Lymphoblasts are precursors for lymphocytes
various cytokines regulate the rate of division and differentiation
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what controls the production of RBCs?
erythropoetin released from pertitubular endothelial cells in the kidneys
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describe neutrophils
- multi-lobed nucleus
- functions = chemotaxis and phagocytosis
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describe eosinophils
- bilobed nucleus
- orange granules
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describe basophils
- large dark purple granules
- release histamine and heparin
- mediate acute inflammation
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describe platelets
- small round blue particles from cytoplasm of megakaryocytes in bone marrow
- activation leads to adhesion and aggregation and acts as a binding site for clotting factors
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what are the three types of muscle?
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describe skeletal muscle
- striated
- voluntary
- pink due to myoglobin and vascularisation
- fibres are long, multi-nucleated and cylindrical
- RED = slow lots of myoglobin
- WHITE = fast - easily fatigued
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what determins power output of a muscle?
- number of fibres
- amount of hypertrophy
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what is the structure of muscle
muscle > fascicle > fibre (cell) > fibrils packed in parallel with organelles organised between them, the sarcotubular system allows for depolarisation to be spread across the fibre by T tubules > myofibrils are made up of myofilaments which are actin and myosin
- the muscle sheath is epimysium
- surrounding each fascicle is perimysium
- surrounding each fibre is endomysium
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describe the actin filament
- double helical strand
- troponin is distributed along it attached to tropomyosin
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what is the sliding filament hypothesis?
- 1. a nerve impulse arrives at neuromuscular junction causing release of ACh, depolarisation of the end plate and release of calcium
- 2. calcium binds to troponin which changes its shape and moves tropomysin away from the binding site of the actin so that the myosin filaments can form a cross bridge
- 3. the breakdown of ATP releases energy so myosin can pull the actin - shortening/contracting the muscle
- 4. myosin detaches from the actin and the cross bridge is broken down when ATP binds to the myosin to the myosin head when the ATP is broken down by myosin ATPase the power strike can be repeated
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how are muscles innervated?
nerves attach at the motor end plate, one per fibre
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can muscle regenerate?
- skeletal muscle has a small regenerative capacity but gross damage is repaired by CT and leaves a scar
- in nerves or blood supply is interrupted muscle fibres degenerate and are replaced by fibrous tissue
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describe smooth muscle
- non - striated
- involuntary
- found in walls of GI tract, resp tract, walls of ducts, glands, arteries, veins, large lymphatics and in the muscles of the eye
- the cells are long and spindle like often embedded in thin elastic fibres
- their contraction is slower than skeletal muscle and their actin and myosin arrangement is less ordered.
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describe cardiac muscle
- striated
- involuntary
- found in the heart
- has elongated nuclei, which are central in the fibres, intercalated discs, fibres contain large numbers of sarcosomes, the T tubules lie at the Z bands
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what are purkinjie fibres?
- ensure rapid spread of impulses
- contain fewer myofilaments, fibres and far fewer intercalated discs
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can cardiac muscle regenerate?
NO repairs with fibro-connective scar tissue
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how often are contractile proteins replaced?
- every two weeks
- muscle continuously remodels
- can atrophy and hypertrophy very quickly
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what is myasthenia gravis?
- auto-immune destruction of end plate ACh receptors
- more common in females
- characterised by muscle weakness without sensory loss
treat with ACh esterase inhibitors
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list conditions that affect the neuromuscular junction
- myasthenia gravis
- botulism - toxins block ACh release
- organophosphate poisoning - irreversible binding of AChE > asphyxiation
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what is Duchenne MD?
- complete lack of dystrophin, muscle tears itself apart calcium enters and causes death and necrosis
- death in late teens from resp failure
- recessive defect on X chromosome
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describe muscular dystrophies
- genetic disorders
- muscle weakness and wasting
- replaced by fat and CT
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what are the main division of the nervous system?
- CNS
- PNS > ANS > sympathetic/non-sympathetic
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what is the structure of the CNS?
- vast numbers of neurones supported by neuroglia, components sorted into grey and white matter
- the CNS is the brain and the spinal cord
- most neurones in the CNS are multipolar
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what is grey matter?
nerve cell embedded in neuroglia
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what is white matter?
the processes is the processes of the nerve cells embedded in neuroglia
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what is glia made up of?
- astrocytes
- oligodendrocytes
- microglia
- ependymal cells
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what is the structure of the PNS?
- cranial and peripheral nerves made up of bundles fibres
- divided into motor/efferent and sensory/afferent
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what happens in the pre-embryonic period?
- fertilisation > zygote
- cleavage > morula
- compaction > embryoblast/trophoblast/blastocyst cavity
- hatching > loss of zona pellucida
- beginning of implantation
- week 2 - trophoblast > syncytiotrophoblast + cytotrophoblast and embryoblast > epiblast + hypoblast (bilaminar disc)
- completion of implantation
- formation of primary yolk sac lined by hypoblast cells
- formation of secondary yolk sac from pinching off of primary yolk sac
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what marks the start of the embryonic period?
formation of the primitive streak
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what happens during the embryonic period?
- all major structures and systems formed
- GASTRULATION - primitive streak defines the axis it is made up of the pit, node and streak
- epiblast cells migrate towards the primitive streak and invaginate displacing the hypoblast cells and creating the trilaminar disc
- NOTOCORD - the epiblast cells that invaginate through the cranial part of the primitive pit form a solid rod of cells down the midline - this drives neuralation
- NEURALATION - formation of the neural plate and the neural tube - notocord causes thickening of overlying ectoderm and the edges fold round creating a tube.
- MESODERM - the paraxial mesoderm becomes organised into segments, in pairs called somites, there are 31 pairs
- FOLDING - cephalocaudal and lateral
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what are the three layers of the trilaminar disc?
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what do somites become?
- dermatome - skin section - dermis
- myotome - muscle section
- sclerotome - hard tissue section - bones
give rise to repeating sections such as vertebrae, ribs and intercostal muscles.
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what are the derivatives of the ectoderm?
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what are the derivatives of the mesoderm?
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what are the derivatives of the endoderm?
- epithelium of the resp and GI tracts
- glands
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