TOB Flashcards
Types of electron microscopy
Scanning
Transitional
Types of light microscopy
Bright field - normal
Dark field - light shined at angle - see reflections only
Phase contrast - light passed through sample changes phase, exaggerate using phase plate
Differential interference contrast - like phase contrast but. Edge highlights
Fluorescence - add fluorescent stain or gene - add specific wavelength and it glows a specific colour
Confocal - fluorescence that uses focused beam so scans
Types of stains for histology
Eosin - stains basic stuff red
Haemotoxylin - stains acid stuff blue
Periodic acid shiff - stains carbohydrates and glycoproteins magenta
What are the two layers of the basement membrane?
Basal lamina
Lamina reticularis
What is mucus?
Liquid containing highly glycosylated polypeptides
What stains mucous glands?
What stains serous glands?
PAS
H and E
What are the three types of secretion?
Merocrine - extends membrane as vesicle fuses
Apocrine - shrinks membrane as vesicle forms
Holocrine - cell disintigrates
On which side of golgi are cis and trans?
Cis faces ER
Trans faces PM
What is the covering of carbohydrates over a cell membrane called?
Glycocalyx
What are sebaceous glands?
Associated with hair follicles
Branched acinar structure
Holocrine secretion of sebum
Sebum helps protect hair and skin
What are the layers of the gi mucous membrane?
Lumen
Mucosa - epithelium, lamina propria, muscularis mucosa
Submucosa
Muscularis externa - circular, longitudinal
Serosa / adventitia
What is found in the lamina propria?
Payers patches
Mucosal glands
What is found in the submucosa?
Glands, vessels, lymphatics
What the three sorts of cytoskelelton? What do they do?
Microfilaments - e.g. Actin around edge of cell providing support, shape and movement
Intermediate filaments - tough support network, anchors cell junctions, stabilises cell e.g keratin
Microtubules - long hollow tubes, allow movement within the cell, dynein and kinesin attach organelles to the microtubules. E.g. Spindle fibre or cilia / flagella movers.
What produces spindle fibre? What sort of cytoskeleton is it?
Centrioles within centrosomes
Microtubule
What is the distinction between flagella and cillia?
Cillia move things over surface of cell
Flagella move cell
What is the microtubule structure of flagella?
Two central single tubes surrounded by nine double tubes
What is a peroxisome?
Similar to a lysome but smaller, detoxifies chemicals via oxidation
What is found on the outer coat of a gram positive bacteria?
Peptidoglycan
What is found on the outer coat of a gram negative bacteria?
Lipopolysacaride
What are the three main stages of in utero development?
Weeks 1-2 pre embryonic
Weeks 3-8 embryonic
Weeks 9-birth fetal
In what ways can a fetus grow?
Proliferation of cells
Hypertrophy of cells
Secretion of extracellular matrix
What occurs in week one of development?
Morula formation
Differentiation between inner and outer cell masses
Fluid leaks in forming blastocele within blastocyst
Formation of trophoblast and embryoblast
Breakdown of zona pellucidia
Binding to external endometrium
What cavities form in the second week of development?
Amniotic cavity within epiblast
Hypoblast migrates around edge of blastocele forming primitive yoke sac
Extraembryonic mesoderm forms between yoke sac and cytotrophoblast. Lancunae form in this mesoderm, merging to. Frm extraembryonic or chorionic cavity.
Differentiate the extraembryonic mesoderms
Splanchnic - lines the yoke sac
Somatic - lines the amniotic cavity
Chorionic plate - lines chorionic cavity
What are the functions of connective tissue?
Support Substance/form Protection Attachment Defence against infection Repair
What is ground substance?
What are its functions?
Hyaluronic acid (large GAG) with proteoglycan branches (protein cores with GAG branches)
Highly negatively charged attracting water forming a gel
Porous
Good at resisting compression
Filtering role in bowmans capsule
What cell types are commonly found in connective tissue?
Fibro/chondro/osteo - blasts/cytes Myofibroblasts Adipocytes Macrophages Mast cells
What are the 4 types of collagen?
1 - 90%, forms fibres
2 - doesn’t form fibres, found in cartilage
3 - reticulin, forms mesh around tissues/organs
4 - doesn’t form fibres, part of basement membrane
What comprises elastic fibres?
Fibrillin (orders fibres)
Elastin (secreted as tropoelastin)
Structure and examples of loose connective tissue
Many fibroblasts
Disordered sparse fibres
Eg submucosa, lamina propria, mammary glands
Structure and examples of dense regular connective tissue
Densely packed collagen with few fibroblasts
Collagen direction regular
Eg tendons, ligaments
Structure and examples of dense irregular connective tissue
Densely packed collagen with few cells
Collagen direction irregular
Eg dermis, periosteum etc.
What are the 4 layers of the epidermis from external to internal?
Stratum corneum
Stratum granulosum
Stratum spinulosum
Stratum basalis
What causes someones skin to be darker in colour?
Increased melanin
Number of melanocytes the same
How can skin differ region to region?
Colour
Hair
Laxity
What are the functions of skin?
Protection (physical, chemical, radiological, pathogens) Sensation Thermoregulation Water balance Metabolism Sexual attraction
What cell types are found in the epidermis and where
Keritinocytes - from basalis to corneum
Melanocytes - basalis
Langerhans - spinosum
How do keritinocytes develop?
Mitosis in stratum basalis
Gain many desmosme junctions joined by tonofilaments through stratum spinulosum
Keratinohyline granules visible in stratum granulosum
Keratinohyline released converting tonofilaments into keratin cell dehydrates, organelles degrade in stratum corneum
All takes 28 days
What is found in sebum?
Fatty acids, cholesterol, glycerol
Where are sebacious glands found
One for each hair follicle
Fordyce spots of the genitals
Tysons glands of the foreskin
What are the two types of sweat glands? Where are they found? Hw do they secrete? How are the secretions different?
Merocrine - found over most skin
Appocrine - secretes in a merocrine fashion found in groin, axilla, aerola and beard
Appocrine glands secrete proteins, initially odourless until vrokend down by bacteria
What is. Psoriasis?
? Genetic ?immune
Execess proliferation of stratum basalis causing thickening of skin
What causes vitiligo? What is the risk?
Autoimmune destruction of melanocytes
Increased risk of sunburn and cancer
What is alopecia areta?
Immune destruction of hair follicles
Usually patchy
What causes acne?
Obstruction of sebaceous glands ducts due to abnormal differentiation followed by infection of trapped sebum
What occurs to epiblast cells during gastrulation?
Invaginate down primitive streak
Displace hypoblast forming endoderm
Fill gap between hypoblast and epiblast forming mesoderm
Epiblast becomes ectoderm
How does the notochord form?
Pre notochordal cells invaginate through the cranial primitive pit, forming a midline rod running cranially to the procordal plate (just caudal to the buccopharyngeal membrane
Initial fusion to hypoblast, then as this is replaced by endoderm detach forming definitive notochord
What are the functions of the notochord?
Drives neurolation
Defines midline
Provides framework
Becomes part of nucleus pulposus of intervertebral discs.
What structures are derivied from ectoderm?
Epidermis
Nervous
What is a cause of dextrocardia/situs invertus?
Derrangement of cilliated cells at primitive node causing disturbed left to right development.
From which germ layers is epithelium derived?
Ectoderm - all external epithelium (skin and cornea)
Mesoderm - all internal tubes closed to outside (and GU tract)
Endoderm - all internal tubes open to outside (except GU tract)
What are the two broad classifications of twins?
Dizygotic
Monozygotic
What are the different classifications of monozygotic twins? What do they share?
Split morula - own placenta, own amnion
Split inner cell mass - shared placenta, own amnion
Two primitive streaks - shared placenta, shared amnion
What is the major fibre of cartilage? What effect does its properties have on the cartilage? What else contributes to this property?
Type ii collagen
Doesn’t form fibres making the cartilage strong but flexible
Large amounts of ground substance
How does cartilage develop?
Mesenchymal cells - chondroblasts - groups of chondroblasts - secretion of ground substance and collagen pushing chondroblasts apart - chondroblasts divide to groups of maintaining chondrocytes
How can cartilage grow?
Appositional - fibroblasts in perichondrium differentiate into chondroblasts, secrete matrix then differentiate into chondrocytes
Interstitial - chondrocytes divide forming clusters of chondroblasts termed isogenous groups which separate as matrix produced.
What are the three types of cartilage? Where are they found?
Hyaline - synovial joints, sterno costal junction, framework for development of skeleton, epiphysal plates, nasal septum, bronchi/trachea
Elastic - pinnia of ear, epiglottis, eustachian tubes
Fibro - high impact areas - menisci of knee, pubic symphysis, annulus fibrosis, tmj
Why does articular cartilage heal so poorly?
Avascular
No perichondrium on articular surface
What cells are found in fibrocartilage? What does this mean for the matrix?
Chondroblasts (secrete type 2 collagen)
Fibroblasts (secrete type 1 collagen)
What cartilages lack perichondrium?
Articular hyaline
Fibro
What are the different sorts of bone?
Compact/cortical
Spongy/cancellous
Woven
What are the features of cortical bone?
Arranged in osteons of concentric lamellae with interstitial lamellae between them surrounded by circumferential lamellae.
What is the structure of an osteon?
Osteocytes sat in lacunae between circumferential lamellae
Communicate via canaliculi
Central havasian canal
Perforating volkmans canal
What is the structure of cancellous bone?
Circumferential lamellae forming trabeculae but no canals.
How is bone remodelling performed?
Osteoclasts cut a cone out of the bone.
This is filled with loose connective tissue
Then replaced by osteoblasts with new bone forming an osteon
How do bones develop?
Endochondrial ossification
Intermembranous ossification
How does endochondrial ossification occur?
Mesenchymal cells to chondroblasts to hyaline cartilage model.
Collar of compact bone around shaft
Central chondrocytes hypertrophy and matrix calcifies
Nutrient artery penetrates shaft
Chondrocytes differentiate to osteoblasts forming primary ossification centre replacing cartilage with bone matrix
Osteoclasts break down middle of bone forming medullary canal
Secondary arteries penetrate epiphysis - secondary ossifcation centres.
Hyaline cartilage remains at epiphyseal growth plate and at either end for articulation
Describe intermembranous ossification
Development of osteoblasts in mesenchyme (ossification centres)
Secretion of ecm
Osetoblasts to osteocytes
Calcification of ecm
Condensation of menchyme around trabeculae forming periosteum. Layer under periosteum forms cortical bone.
What are the layers of the epiphysal growth plate?
Zone of resting cartilage Zone of proliferation Zone of hypertrophy Zone of calcified cartilage Zone of reabsorption
How do bones grow in width?
Appositional growth from periosteum
What occurs in the zone of calcified cartilage and zone of reabsorption in the epiphysal growth plate?
Zcc - calification = death of chodroblasts
Zr - capillaries permiate, reabsorption leaving bony spicules on which bone is deposited by osteoblasts
What effects bone growth?
Hormones - growth hormone, thyroid hormone, sex hormones
Raw materials - need minerals and vitamins (for collagen production and calcium absorption)
How do the sex hormones influence bone growth?
Increase osteoblast activity hence puberty growth spurt
However, oestrogens also ultimately stop epiphysal plate growth hence shorter females.
What are the stages of fracture repair?
Haemotoma
Phagocytosis
Fibrocartilage soft callous (3 weeks to a month)
Osteoblasts produce cancellous bone hard callous (about 3 months)
Remodelling
What is brittle bone disease?
Osteogenesis imperfecta
Autosomal dominant
Effects synthesis of type 1 collagen
Causes - repeated fractures, bowed bones, blue sclerae, joint laxity, hearing loss
What is the effect of precocious puberty on bone development?
Less growth prior to puberty so stunted growth overall as plates close early
What is osteoporosis?
Decreased bone mass caused by excessive osteoclast activity in relation to osteoclast activity.
How is bone density measured? What are the values given?
What are the diagnostic values?
DEXA scan
Z score - value compared against similar demographic to yourself
T score - value compared against average 30 year old female
Measured in standard deviations
T score of less than 1 is osteopenia, less than 2.5 is osteoporosis
What are the risk factors for osteoporosis?
Gradual decline with age Post menopausal women Hyperparathyroidism or hyperthyroidism Smoking Glucocorticoids Heparin!
What are symptoms of osteoporosis?
Fractures
Height loss and kyphosis due to vertebral fractures
What is the commonest form of dwarfism?
Achodroplasia
Autosomal dominant
Defect in fibroblast growth factor receptor
- decreased endochondrial ossification
- decreased chondrocyte proliferation inn epiphyseal growth plate
- decreased cellular hypertrophy
- decreased cartilage matrix
- bar of bone seals off epiphyseal growth plate
What are rickets and osteomalacia?
Decreased bone mineralisation most commonly as a result of low vitamin D causing low calcium and thus increased reabsorption from bone.
What treatment is given to rickets? How would this differ in kidney failure?
Give vitamin D (ergocalciferol)
If kidneys fucked give calcitriol
How do muscles develop?
Mesoderm derived myoblasts form fuse to form multinucleated myotubes. Myofilaments develop in the myotubes pushing the nucleus to the edge.
What are the layers of a skeletal muscle?
Myofilament - contractile proteins Myofibrils - collections of myofilaments Muslce fibre - individual cell Endomysium Muscle fascicle Perimysium Muscle Epimysium
What are the histological differences between the fascial layers of a skeletal muscle?
Epi and peri both dense irregular
Endo is loose areolar
What sorts of muscle fibres are there?
Red - slow twitch, very vascular, lots of myoglobin, lots of mitochondria
White - fast twitch, large, many myofibrils,
What is the histological appearance of a skeletal muscle fibre?
Multinucleate (peripherally displaced)
Striated
T tubules on the A-I band junction
T tubule arranged in triad with 2 terminal cisterna
What contractile filaments are attached to the m line in skeletal muscle?
Myosin
What letter region is actin attached too in skeletal muscle?
What else is attached to this region?
Z disc
Titin
What are the three bands/zones found in skeletal muscle? What do they contain?
H zone - area of myosin only
A band - area spanning entire length of myosin including actin overlap
I band - area of actin only, spans two sarcomeres
When skeletal muscle shortens what bands change? How?
Actin slides over myosin pulling z disc towards m line
H zone shrinks (more overlap)
A band stays constant (no change in length of myosin)
I band shrinks (less non-overlapping actin)
What is the process of skeletal muscle contraction?
Atp binds to myosin head causing it to release from actin
Atp to adp and pi causing the head to cock
This allows binding to the actin
The adp and pi are released causing a stroke movement
What is the physiological basis for rigor mortis?
No atp means myosin head cant be released from actin
How is skeletal muscle activated by a nerve impulse?
Acetyl choline released from terminal and binds to NACh receptors
Depolarises membrane and t tubules
Releases calcium ions from sarcoplasmic reticulum
Calcium binds to troponin c which moves troponin i and troponin t. The movement no troponin t moves tropomyosin exposing myosin binding sites on actin.
What are the histological features of cardiac muscle?
Mononucleated (central) Striated Intercalated discs No myofibrils (mass of myofilaments) No triad around t tubules T tubules descend at z disc
How do smooth muscle cells appear histologically?
Spindle shaped
Actin and myosin arranged between dense bodies on surface and within cell.
Not striated, no t tubules
How is smooth muscle contraction different from skeletal or cardiac?
Slow
Sustained
Passes between muscle cells through gap junctions
How is smooth muscle activated?
Depolarisation
Calcium release - binds to calmodulin activating it
Activated calmodulin activates MLCK
MLCK phosphorylates myosin heads allowing binding and contraction
What muscle cells can and cant regenerate?
Skeletal - limited from satellite cells
Cardiac - cant
Smooth - mitotically divides
What are causes of muscle atrophy?
Disuse
Denervation
Age
What do muscles gain during hypertrophy?
Increased myofibrils
Increased glycolysis enzymes
Increased mitochondria
Increased blood flow
How does stretching change muscles?
Increased number of sarcomeres increasing length
What is. Myasthenia gravis?
Autoimmune destruction of muscle ACh receptors, loss of folds in sarcolemma and widening of synaptic cleft
Why does myasthenia gravis not show symptoms until the disease is advanced? Why does it effect repeatedly used muscles?
Only 25% of receptors needed to trigger a contraction therefore have to loose many for a clinical effect
Successive contractions result in less ACh release so there is fatigability
Hw does myasthenia gravis present?
How is it treated?
Dropping eyelids
Blurred. Vision
Difficulty with speech, chewing, swallowing
Respiratory imparment
Acetylcholinesterase inhibitors such as neostigmine
What bacteria causes botulism?
Clostridium botulinum
How does clostridium botulinum cause botulism?
Botulism toxins inhibit release of ACh
What is the mechanism of organophosphate poisoning?
Inhibits acetylcholinesterase irreversibly increasing ACh ++ resulting in continued muscle contraction
