ToB Flashcards
State the relationship between
- meters
- millimetres
- micrometres
- nanometres
- angstroms
Metre = m
Millimetre = 10 to the -3 m
Micrometre = 10 to the -6 m
Nanometre = 10 to the -9 m
Angstrom = 10 to the -10 m
State the meaning of the term tissue.
A collection of cells specialised to perform a particular function.
What to aggregations of tissues constitute?
Organs.
Define histology.
The study of the structure of tissues by means of special staining techniques combined with light and electron microscopy.
Why is histology valuable in diagnosis?
In many diseases such as Crohn’s, treatment is not given until the histopathologists have given a diagnosis. A biopsy and histology is the final proof for many diseases, like lung/breast cancer.
Define the term biopsy.
The removal of a small piece of tissue from an organ or part of the body for microscopic examination.
Describe a smear and give an example of a tissue that can be sampled by this method.
Collecting cells by spontaneous/ mechanical exfoliation, and smear on the slide.
Example tissue: cervix, buccal cavity.
Describe a curettage and give an example of a tissue that can be sampled by this method.
Removal of tissue by scooping/ scraping.
Example of tissue: endometrial lining of the uterus.
Describe a needle biopsy and give an example of a tissue that can be sampled by this method.
Put needle into tissue to gather cells.
Example of tissues: brain, breast, liver, kidney, muscle.
Describe a direct incision biopsy and give an example of a tissue that can be sampled by this method.
Cut directly into the tissue of interest and remove the tissue.
Example of tissue: skin, mouth, larynx.
Describe an endoscopic biopsy and give an example of a tissue that can be sampled by this method.
Removal of tissue via instruments through an endoscope.
Example of tissue: lung, intestine, bladder.
Why does tissue in a slide need to be fixed?
What does it do the proteins?
To confer stability; unfixed tissues are subject to putrefaction and attack by autolytic enzymes.
It makes proteins insoluble. Macromolecular cross linkage.
Name two common fixatives.
Formaldehyde and glutaraldehyde.
Describe how tissue processing can lead to the formation shrinkage artefacts.
During slide preparation the tissue is dehydrated then rehydrated, which can lead to abnormalities in the final slide.
Describe the 5 steps of tissue preparation for microscopy.
- FIXATION: add formaldehyde/glutaraldehyde, cross linking adjacent proteins, arresting biological activity.
- DEHYDRATION AND CLEARING: Ethyl alcohol replaces water, cleared with xylene/toluene to make miscible with wax.
- WAX EMBEDDING: wax impregnation at 56C, solidifies so it can be sectioned.
- STAINING: xylene clears wax, hydrated with descending % of alcohol, as most stains are water soluble. Dyes selectively stain components based on chemical nature.
- MOUNTING: Slides are dehydrated, placed in xylene, mounted on xylene based medium, coverslip placed on top.
What does H&E stand for?
Haemotoxylin and Eosin
What does PAS stand for?
Periodic Acid-Schiff
What does haemotoxylin stain in cells, and what colour does it stain them?
It stains ACIDIC compoonents of cells, PURPLE/BLUE.
- Nucleolus (RNA)
- Chromatin (DNA)
What does eosin stain in cells, and what colour does it stain them?
It stains BASIC components of cells, PINK.
- Most cytoplasmic proteins
- Extracellular fibres
What does Periodic Acid-Schiff stain, and what colour does it stain them?
It stains CARBOHYDRATES and GLYCOPROTEINS.
MAGENTA
What is PHASE CONTRAST microscopy?
Advantages?
Using the interference effects of two combining light waves.
Advantage: It enhances the image of unstained cells.
What is DARK FIELD microscopy?
Advantages?
Exclude unscattered beam (light/electron) from the image.
Advantages: can use live and unstained samples.
What is FLUORESCENCE microscopy?
Advantages?
Targets molecule of interest with fluorescence.
Advantage: can use multiple fluorescent stains on one specimen.
What is CONFOCAL microscopy?
Advantages?
Tissue labelles with one or more fluorescent probes.
Advantage: Eliminates ‘out of focus flare’, 3D imaging from a series of 2D images, imaging of living specimens.
Define epithelia
Sheets of continguous cells, of varied embryonic origin, that cover the external surface of the body and line internal surfaces.
2 examples of an exterior surface with an epithelial lining.
Which germ layer do they come from?
Skin
Cornea of eye
ECTODERM
3 examples of interior surfaces opening to the exterior that have epithelial linings.
Which germ layer do they come from?
Gastrointestinal tract. ENDODERM
Respiratory tract. ENDODERM
Genitourinary tract. MESODERM
5 examples of interior spaces not opening to the exterior which have epithelial linings.
Which germ layer do they come from?
Pericardial sac
Pleural sac
Peritoneum
Blood vessels
Lymphatic vessels
All come from the MESODERM
What are the two main ways of classifying epithelium? (explain both)
SIMPLE: one cell layer thick
STRATIFIED: more than one cell layer thick
What are the 4 types of simple epithelia?
Squamous
Cuboidal
Columnar
Pseudostratified
What are the 5 types of stratified epithelia?
Squamous - keratinised
Squamous - non keratinised
Cuboidal
Columnar
Transitional
Name some locations and functions of simple squamous epithelia.
Locations: blood vessel lining (ENDOTHELIUM), lining of body cavities (MESOTHELIUM, pericardium, pleura, peritoneum), alveoli, Bowman’s capsule, Loop of Henle. inner and middle ear.
Functions: lubrication (viscera), gas exchange, barrier (Bowman’s), active transport via pinocytosis (meso/endothelium).
Name some locations and functions of simple cuboidal epithelium.
Locations: Glands (thyroid follicles, small ducts of many exocrine glands), kidney tubules, germinal epithelium surface of ovary.
Functions: absorption and conduit (exocrine glands), absorption and secretion (kidney tubules), barrier/covering (ovary), hormone synthesis, storage and mobilisation (thyroid).
Name some locations and functions of simple columnar epithelium.
What feature might it have on its apical surface?
Locations: stomach lining and gastric pits, small intestine and colon, gallbladder, large ducts of some exocrine glands, uterus, oviducts, ductuli efferents of testis (epididymis)
Functions: absorption, secretion, lubrication, transport.
MICROVILLI
What is a zona occludens?
A tight junction
What does occludin do?
Binds adjacent plasma membranes together tightly, so membrane proteins can not bypass and are restricted to the apical surface, and segregate others to the lateral and basal surfaces.
Name some locations and functions of simple pseudostratified epithelia.
What other features might they have?
Locations: URT (lining of nasal cavity, trachea and bronchi), epididymis and ductus deferens, auditory tube, tympanic cavity, lacrimal sac, large excretory ducts.
Functions: secretion and conduit (URT, ductus deferens), absorption (epididymis), mucus secretion (URT), particle trapping and removal (URT).
CILIA, MUCUS SECRETION
Name some locations and functions of stratified squamous keratinised epithelium.
Locations: surface of skin, limited distribution in oral cavity.
Functions: prevents water loss, protection against abrasion and physical trauma, prevents ingress of microbes, shields against UV light damage.
Name some locations and functions of transitional stratified epithelium.
Locations: renal calcyes, ureters, urethra, bladder
Functions: distensibility, protection of underlying tissue from toxic chemicals.
What and where is the basement membrane?
The thin, flexible, acellular layer which lies between the epithelial cells and the subtending connective tissue.
What lays down the basal lamina?
The epithelial cells
What is the structure of the basement membrane?
The basement membrane and various other layers. There is also a reticular fibre (type III collagen) layer, the thickness of which can be changed.
What is the function of the basement membrane?
A strong, flexible layer to which epithelial cells adhere. Also serves as a cellular and molecular filter.
How is the basement membrane related to prognosis of cancer?
The degree to which malignant cells penetrate the basement membrane is related to prognosis.
Cell renewal rate in epithelial tissues is normally constant. What can accelerate it?
Injury.
How long does it take from cell division in the basal layer of the epidermis to finally being sloughed off?
28 days.
How often are small intensinal epithelial cells replaced from the base of the crypts?
4-6 days
What are sterocilia?
Where might they be found?
Very long microvilli, which may have an absorbative function.
Ductus deferens and epididymis.
What is the average size of a human cell?
10 to 20 micrometers
What makes us the epithelial basement membrane?
Basal lamina (lamina lucida and densa) and lamina reticularis
What are microvilli?
Extensions of the cell membrane, core of which is a cluster of actin fialmenets embedded in villin
What is metaplasia?
Give an example
Transforming to another cell type
Stratified squamous epithelium is replaced by simple columnar epithelium with goblet cells
What does the basement membrane do?
Molecular filter
Regulates cell migration
Epithelial regeneration
Cell to cell interactions
What is a zonula occludens?
A tight junction between cells that makes it virtually impermeable to fluid
What is a gap junction?
Permits cells to communicate
Can be closed
Directly connects cytoplasm
Analagous to plasmodesmata in plants
What is a desmosome?
What is a hemidesmosome?
Desmosome: macula adherens, anchoring junction for cell to cell adhesion. Lateral, help to resist shearing forces in simple and stratified squamous epithelium
Hemidesmosome: mediate adherence to the basal lamina.
How are most glands formed?
What are the secreting cells of a gland called?
By epithelial downgrowths into surrounding connective tissue
Parenchyma
Define a gland.
An epithelial cell or collection of cells that are specialised for secretion
How are glands classified by destination?
Exocrine: a gland with ducts that open into the lumen of an organ or onto the surface of the skin
Endocrine: a gland that secretes directly into the bloodstream or lymphatic system, ductless. Arranged as cords, follicles or clusters around a profuse blood supply for transport
How are glands classified by structure?
Unicellular, such as goblet cells, release secretion onto surface epithelium
Multicellular: duct system, extends from surface to underlying connective tissue
Uncoiled, coiled
Simple, complex
Unbranched, branched
What is a mixed gland?
Give an example
A gland with both endocrine and exocrine components
Pancreas
Exocrine secretes enzymes through ducts to the duodenum, D2. Acinar cells
Endocrine, Islets of Langerhans, Insulin and Glucagon to the blood
What is a goblet cell?
What does it secrete?
What type of epithelium is it?
Unicellular gland
Secretes mucin which combines with water to form mucus
Mucus onto the apical surface to lubricate respiratory tract, intestines etc
Simple columnar eputhlium
What is an acinus?
Give an example of an organ in which acini are found in
Swelling of secretory glands at the end of a tube
The pancreas is multi acinar
What types of simple glands are there?
Give examples
Simple tubular: intestinal cells
Simple coiled: merocrine sweat glands
Simple branched tubular: gastric glands, mucous glands of oesophagus, tongue, duodenum
Simple branched acinar: sebaceoud glands.
Simple acinar is only a developmental stage
Acinar is aka alveolar
What typre of compound glands are there?
Give examples
Compund tubular: mucous glands in mouth, bulbourethral glands in males, testes in the seminiferous tubule
Compound acinar: mammary glands
Compound tubuloacinar: salivary, pancreas, glands of respiratory tract
How are glands classified by their method of secretion?
Give examples
Merocrine: exocytosis, most glands. Salivary glands, pancrease
Holocrine: disintegration of the entire cell, sebaceous gland disintegrate to fill hair follicle with sebum
Apocrine: Non membrane bounded lipid secretion, mammary glands, myoepithelial cells assist
How are glands classified by their nature of secretion?
How effectively are they stained by H and E?
Mucous: contain mucus and are high in mucins, which are highly glycosylated polypeptides. They stain poorly with H and E.
Serous: often contain enzymes, are watery and free of mucus. Stain pink with H and E, so are eosinophilic.
Describe the process of merocrine secretion
Membrane bound vesicle approaches cell surface
Fuses with plasma membrane
Contents of vesicle released into extracellular space
Plasma membrane is transiently larger
Membrane is retrieved which stabilises the cell surface area
Describe apocrine secretion
Non membrane bound lipid particle approaches the cell surface
Fuses with the plasma membrane, pushes up apical membrane
Thin layer of apical cytoplsam drapes around the droplet, surrounding droplet pinches off the cell
Plasma membrane transiently smaller
Membrane added to regain cell surface area
Describe holocrine secretion
Disintegration of entire cell
Release of contents
Discharge of the whole cell
What is endocytosis?
Engulfing of material initially outside of the cell
Opposite of exocytosis
Coupled wtuih exocytosis in transepithelial transport
What is transepithelial transport?
When a molecule is too large to penetrate membranes it can be shunted across from one bodily compartment to another
Material is endocytosed at one surface
Transport vesicle shuttles it across the cytoplasm
Vesicle and material is exocytosed at the oppostie surface
Describe the structure of the Golgi apparatus
Stack of disc shaped cisternae
One side is flate, the other side is concave
Discs have swellings at their edges where vesicles bud off: migratory Golgi vacuoles
Cis face to trans face
What is the function of the golgi apparatus?
Sorting into different compartments
Packaging through condensation of contents
Adding sugars to proteins and lipids: GLYCOSYLATION, in the cisternae, vesicles move to the flat face
Transport
What are the destinations of products from the golgi apparatus?
Majority extruded in secretory vesicles
Some retained for use in the cell e.g lysosomes
Some eneter the plasma membrane , glycocalyx
Or are secreted
How does glycosylation in the golgi apparatus increase specificity?
What happens if enzymes destory the glycocalyx ?
SUGARS MAKE MOLECULES MORE SPECIFIC
Branching sugars offer complex shapes for specific interations in the glycocalyx
Destruction of the glycocalyx by enzymes alters specificity of cells: adhesions to substrates and neighbouring cells, communication with neighbouring cells, contact inhibition of movement and division, mobility of cells
Name 4 types of control of secretion? Examples
Nervous: sympathetic netvous stimulate of the adrenal medulla leads to the release of adrenaline
Endocrine: ACTH stimulate release of cortisol from the cortex of the adrenal glands, zona fasciculata
Neuroendocrine: Nervous cells of the hypothalamus control the release of ACTH by CRH
Negative feedback chemical mechanism: inhibitory effect of high t3/4 on TRH and TSH
What are the 3 major salivary glands?
What is the nature of secretion from each?
Parotid: serous
Sub-mandibular: mixed, mucous and serous
Sub-lingual: more mucous but mixed
Classify the following glands as exocrine or endocrine
Goblet cells in jejunum/colon, Pancreas, Thyroid Gland, Parotid glands, Parathyroid glands, Adrenal glands, Sub mandibular glands
Exocrine: Goblet cells, Parotid glands, Sub mandibular glands
Endocrine: Thyroid, Parathyroid, Adrenals
Mixed: Pancreas
What is a serous demilune?
Artefactual structure squeezed out by conventional fixation
Salivary glands
A gland with this structure produces both serous and mucous secretions, mixed
Mucosal and serosal cells actually aligned in the acinus
What type of epithelium is found in the thyroid gland?
Simple cuboidal epithelium
What surfaces do mucosal membranes line? Examples
What cells do they have?
Certain internal tubes which open to the exterior
Alimentary tracts
Respiratory tract
Mucus secreting cells to varying degrees
What is the structure of a mucous membrane?
Constitution
Epithelium (type depending on site) lining the lumen of a tube
An adjacent layer of connective tissue, the LAMINA PROPRIA
In the alimentary tract, there is a layer of smooth muscle, MUSCULARIS MUCOSAE
What are serous membranes?
What do they envelope? Examples
Serous membranes are two part membranes that line certain closed body cavities (do not open to exterior)
They envelope the viscera/organs
Examples
Peritoneum envelopes the abdominal organs
Pericardium envelopes the heat
Pleural sac envelopes the lungs
What is secreted by serosal membranes?
What is the function of this?
What are the two layers of a serosal membrane called?
Secretes lubricating fluid
Promotes relatively friction free movement of structures that they surround
Visceral (inside) and parietal (outside)
What does a serosal membrane consist of?
Simple squamous epithelium MESOTHELIUM which secretes a watery lubricating fluid
A thin layer of connective tiossue which attaches to epithelium of adjacent epithelium, and carries blood vessels and nerves
What is the gut mesentry?
Double layer of peritoneal membrane which supports the small intestine
Describe the layer structure of the alimentary tract
Mucosa: epithelium, basement membrane, lamina propria (aggregrates of lymphocytes, Peyers patches, loose connective tissue), muscularis mucosae
Submucosa: connective tissue layer, arteries, veins, nerves
Muscularis externae: circular muscle inside, longitudinal muscle outside, peristaltic waves
Serosa: mesothelium if peritoneal OR Adventitia: loose connective tissue if retroperitoneal (behind)
Describe the layer structure of the oesophagus
Epithelium: stratified squamous non-keratinised
Lamina propria: loose connective tissue with blood and lymph vessels, some smooth muscle and immune cells
Muscualris mucosae: smooth muscle thin layer
Submucose: subtending layer of connective tissue with mucus secreting glands
Muscularis externa: circular and longitudinal smooth muscle, peristalsis
Adventitia: thin outermost layer of connective tissue
Describe the layer structure of the stomach?
Gastric mucosa: secretes acid, digestive enzymes and gastrin. Simple columnar epithelia for absorption. RUGAE: folds of the gastric mucosa forming longitudinal ridges in an empty stomach.
Muscularis mucosae
Sub mucosa
Muscularis externa: oblique, circular and longitudinal layers of smooth muscle
Describe the layer structure of the jejunum
Pilicae circulares: circular folds of mucosa and submucosa that project into the gut lumen.
Jejunal mucosa: epithelia (simple columnar), lamina propria, muscularis mucosae
Submucosa
Muscularis externa: circular and longitudinal smooth muscle
Describe the layer structure of the large intestine/colon
Epithelium: simple columnar for absorption
Crypts of lieberkuhn producing lots of mucus and supplying cells to the surface. Absorbs water and electrolytes on the surface.
Structure same as rest of GI tract: mucosa, submucosa, muscularis externae, serosa
What makes up the conducting portions and respiratory portions of the respiratory tract?
Conducting: nasal cavity to the bronchioles
Respiratory: Bronchioles to the alveoli
What is the layer structure of the trachea?
Epithelium: pseudostratified ciliated
Submucosa: connective tussue with sero mucous glands which decrease as they go closer to the bronchioles
Fibroelastic membrane with trachealis muscle
C shaped Hyaline cartilage: C shaped to prevent oesophageal collapse, also in bronchus but no further.
Adventitia: loose connective tissue.
Describe the layer structure of the bronchus
Pseudostratified epithelium
Smooth muscle
Submucosa
Crescent shaped cartilage
Describe the layer structure of a bronchiole
Simple columnar/cuboidal/ciliated.
Samller bronchioles are not cilitaed. In terminal bronchioles small sacs extend, lined by ciliated cuboidal epithelium
Smooth muscle
Alveoli: no cartilages because surrounding alveoli keep the lumen open
What are the cell types of the alveoli? What are their functions?
One cell thick, purely epithelial
Type 1 cells: squamous, cover 90% of surface area and permit gas exchange with capillaires
Type 2 cells: cuboidal, cover 10% of the surface area. Produce surfactant.
Numeroud macrophages line the alveolar surface, phagocytose particles
Gas exchange across blood air barrier
Alveoli are surrounded by a basketwork of capillaries and elastic fibres
Describe the layer structure of the ureter in the urinary tract
Transitional epithelium
Lamina propria: fibroelastic
Muscularis externa: circular
Describe the layer structure of the bladder wall
Transitional epithelium, impermeable to urine due to thick plasma membrane and intercellular tight junctions
Smooth muscle in the lamina propria
Muscularis externae, three interwoven layers
Describe the layer structure of the urethra
How long is it in males and females?
Transitional epithelium. In penile urethra the epithelium is stratified columnar.
Lamina propria
Muscularis externae, circular and longitudinal
Adventitia
Stellate (star shaped) urethral lumen becomes ovoid as urine passes through
Describe the regenerative capabilites of various glands
Glandular cells of the mucous membranes of the digestive, respiratory and urinary tractscontinue to multiple throughout life, cells from the apical surface are continually replaced
Liver, thyroid and pancreatic cells cease to multiply at puberty, but can regenerate in the case of tissue injury
What is neoplasia?
A malignant neoplasm derived from glandular epithelium is called an adenocarcinoma
Define the term limit of resolution
The minimum distance at which two objects can be distinguished at
Why are electron microscopes capable of finer resolution than light microscopes?
What is the theoretical limit of resolution of light and electron microscopes?
The limit of resolution
is proportional to wavelength
Electrons, much shorter wavelength than visible light
Light: 0.2mm
Electron: 0.002nm
What are the main differences between prokaryotic and eukaryotic cells?
Prokaryotic: no internal membranes, all processes in one compartment
Eukaryotic: compartmentalised by internal membranes, ordely biochemical processes
Describe the properties and functions of membranes
Phospholipid (amphipathic molecules) bilayer
Proteins are freely mobile, fluid mosaic
Some proteins within the membrane are attached to the cytoskeleton
Some proteins are glycosylated, pointing outwards, forms the glycocalyx
FUNCTIONS: intercellualr adhesion, recognition, signal transduction, compartmentalisation, selective permeability, exocytosis and endocytosis
Describe the nucleus
Contains DNA, nucleoproteins and RNA
Dense heterochromatin and lucent euchromatin
Inactive: small and dense
Active: large and sparse
Describe the nucleolus
Electron dense structure
Site of ribosomal RNA synthesis for ribosome assembley, sub units exported
Disappears in cell division
Describe the nuclear envelope
Double layer of membranes
Nuclear pores
Type of special ER, the perinuclear cisterna between inner and outer nuclear membranes, is continuous with the ER
Describe the rough ER
Ribosomes on surface
Protein synthesis site
Generates proteins for transport out of cell or to lysosomes
Flattened cisternae
Extensive
Interconnecting membranes, vesicles
Lysosomal enzymes made here, N linked glycosylation, intial
Describe the structure of cilia
Nine pairs of peripheral microtubules
Two single central microtubules
Plasmolemma covered extensions of cytoplasm
Move material along the cell surface
Describe the smooth ER
No ribosomes
Lipid and steroid synthesis: liver, mammary glands, testis, adrenals
Not as flat as rough ER, less extensive
Intracellular transport
Continous with rough ER enclosing single lumen
Describe the golgi apparatus
Stacks of cisternae, cis and trans face
Prioteins from the rough ER bud off and fuse with the convex cis face
Proteins migrate to the concave trans face
Sort, concentrate, package and modify proteins
O linked glycosylation, add mannose 6 phosphate marker for lysosomal enzymes
Describe lysosomes
Generated by the Golgi apparatus
Hydrolytic enzymes
pH 5
Highly glycosylated membrane for protection
Diverse in shape
Primary and secondary - phagolysosome
Many found in neutrophils and macrophages
Describe peroxisomes
Roughly spherical
Granualr matricx bound by single membrane
Self replicating, no genome
in all cells, especially the liver and kidney
Major sites of o2 utilisation and H2O2 production
Detoxification
Oxidises phenols, alcohols, fomic acid, formaldehyde
Describe mitochondria
Double membrane with inner membrane in ditinct folds, cristae
Generation of ATP by oxidative phosphorylation
Main substrates are glucose and fatty acids
Matrix: enzymes and mitochondrial DNA, own genetic info, can divide. Female lineage
Inner membrane is impermeable to small ions
ATP synthase enzymes
Endosymbiosis theory
Many found in the liver and skeletal muscle
Describe the cytoskeleton
Maintains and changes cell shape
Structural support for the plasma membrane and organelles
Means of movement inside the cell
Contractiblity in muscles
Locomotor mechanisms for amoeboid movements like lymphocytes, and also for cilia and flagella
Describe microfilaments
Part of the cytoskeleton
5nm diameter
Two strings of actin twisted together
Associated with ATP - contractile
Can assemble and dissociate, so is dynamic
Core of actin filaments maintains microvilli
Describe intermediate filaments
Part of cytoskeleton
Not dynamic, 10nm diameter
Commonn in nerve and neuroglial cells
Also common in epithelial cells that are made of cytokeratin. Tough supporting meshwork in cytoplasm and atr anchored to plasmamebrane at strong intracellular junctions - desmosomes
Forming nuclear lamina
Describe microtubules
Part of cytoskeleton
13 alpha and beta subinits polymerise to form the wall of the hollow microtubules
Originate from the centrosome
Found at sites where structures in crlld are moved
Long hollow cylinders of tubulin, 25nm diameter
9+2 arrangement in cilia and flagella
Attachment proteins can attach to organelles and move them along microtubules
Define the term connective tissue
Explain some functions
A tissue of MESODERMAL origin
With three basic components: cells, extracellular fibres and ground substance
If forms a huge continnum throughout the body, linking together muscle, nerve and epithelial tissue, in a strcutural, metabolic and physical way
Its functions include supporting organs, filling spaces between them and forming tendons and ligaments
What are the main functions of connective tissue?
Provide substance and form to body and organs
Medium for nutrient and waste diffusion
Attach muscle to bone, and bone to bone
Cushion between tissues and organs
Defend against infection
Aid in injury repair
What are the main resident cell types in connective tissue?
Fibroblasts: synthesise and maintain extracellular components. Synthesise collagen, elastin and reticular fibres and ground substance. Fibrocytes are mature and less active cells.
Mesenchymal cells: undifferentiated cells, differentiate into other cells and maintain extracellular materials
Macrophages: tissue histocytes derived from monocytes. Ingest foreign material such as bacteria, dead cells and cell debris. Specific names, in liver KUPFER cells, in CNS MICROGLIAL cells, in bone OSTEOCLASTS.
How do different connective tissue types vary in their composition?
Cell type
Abundance and densitry of cells
Constitution of extracellular matrix
Ground substance composition
Fibre type, abundance and arrangement
What are the main visitant cell types in connective tissue?
Mast cells: seen near blood vessels containing granules with histamine and heparin. They release phamacologically active molecules.
Plasma cells: derived from lymphocytes.
Fat cells - adipocytes: occur in small clusters or aggregates acting for storage. They store lipids and act as an insulator and shock absorber, cushioning organs and joints.
Leukocytes (WBCs) - derived from blood vessels, responsible for the production of immunocompetent cells
What does the extracellular matrix of connective tissue define?
Whether the function is of primary mechanical importance or if it is loose packing material
What are the classes of connective tissue?
Embryonic: mesenchyme (gives rise to others) from mesoderm, mucous connective tissue
Connective tissue proper: loose (areolar), dense (regular/irregular)
Specialised: adipose, blood, cartilage, bone, lymphatic tissue, haeemopoietic tissue
What makes up ground substance in connective tissue?
Gel like matric which the fibres and cells are embedded in, and the ECF diffuses through it
Core proteins with glycosaminoglycans attached (GAGs)
, proteoglycans and glycoproteins
Hyaluronic acid molecules with many proteoglycan molecules, incterweave with collagen fibrils
Negative charges on GAGs attract water, forming a hydrated gel
What fibres are found in connective tissue, explain a bit about each
Collagen: occurs as bundles of non elastic fibres of varied thickness. Lots of different types but most commonly type 1, synthesis is on RER of cells.
Reticular fibrils: type III collagen, thin branching fibres. Delicate network around smooth muscle cells, some epithelial cells, blood vessels, adipocytes and nerve fibres. Also makes the structural framework around organs such as the spleen, liver, bone marrow and lymphoid organs.
Elastic: highly elastic, able to stretch 150% of resting length due to lysine content. Composed of amorphous protein, elastin and surrounded by fibrillin.
Explain types of collagen and its distribution in the body
Type I: 90% of collagen, tendons, skin dermis, organ capsules, fribrils, fobres, fibre bundles
Type II: no fibres, hyaline and elastic cartilage
Type III: RETICULIN, fibres around muscle and nerve cells, within lympathic tissues and organs
Type IV: basal lamina of the basement membrane
Most common protein in the body
Tunica adventitia
28 types
Describe the type I collagen fibril structure
Periodic banding every 68 nm
Each fibril, staggered collagen molecules
Each molecule is a triple helix of alpha chains, every third amino acid is glycine, 1.5nm wide
Left handed helices into right handed super helix
What do fibroblasts secrete?
PROCOLLAGEN
Intamitely associated with collagen fibrils
Describe the properties and distribution of elastin
Occurs in most connective tissue to varying degrees
Primary component of elastic fibres, surrounded by microfibrils called fibrillin
Low electron density
Found in the dermis of the skin, tunica media of the arteries, elastic cartilage in the epiglottis, ear pinna and eustachian tube
What condition is caused by abnormal fibrillin?
What are the symptoms of the condition?
Marfan’s
Tall, arachnodactyly, joint dislocation, aortic rupture
What are the different types of loose connective tissue and where are they found?
Blood
Mucous connective tiissue e.g. Wharton’s jelly
Areolar connective tissue, in skin, submucosa, below periteoneal mesothelium, adventitia of blood vessels, surrounding gland parenchyma
Adipose
Reticular tissue: framework of lymphoid tissues and the liver
What are some examples of dense regular connective tissue?
Tendons
Ligaments
Aponeuroses
What are some examples of dense irregular connective tissue?
Skin dermis, periosteum, perichondrium, dura mater, capsules, large septa and trabeculae of organs, deep fascia of muscles
What does loose connective tissue do?
What is it made up of?
What happens to it in oedema?
Forms the septa and trabeculae that make up the framework inside organs and adipose tissue. Divides glands into lobules.
Loosely packed fibres that are seperated by amorphous ground substance. Lots of hyaluronic acid, sparse collagen
In oedema it becomes greatly distended with ECF
What is mucous connective tissue?
Where is it found?
What it is its composition?
Loose connective tissue: Such as Wharton’s Jelly
Only found in the umbilical cord and subdermal CTof the embryo
Made up of large stellate fibroblasts, which fuse with similar adjacent cells. Some macrophages and lymphocytes are present.
The ground substance is soft and jelly like with lots of hyaluronic acid.
Delicate mesh of collagen fibres
What is areolar connective tissue?
Where is it found?
What is its composition?
Loose connetive tissue
Found deep under the skin, in the submucosa, below the mesothelium of the peritoneum, associated with adventitia of blood vessels, surrounds the parenchyma of glands
Contains fibroblasts, macrophages and some mast cells
Collagen fibres are the most abundant, but there are some elastic fibres present
What is reticular connective tissue?
What is it made up of?
Where is it found?
Loose connective tissue
Made up of type III collagen
Forms the framework of lymphoid tissues and the liver
What is adipose tissue?
What are its properties?
Loose connective tissue
Composed mostly of adipocytes, occuring singly or in groups
Between collagen fibres
Nuclei are often compressed against the cell membrane
What is the constitution of dense connetive tissue?
What are some properties?
Close packing of fibres
Proportionally fewer cells
Less ground substance
Achieves mecahnical support and transmit forces (tendons)
How are fibre bundles in dense regular connective tissue organised?
Fibres in parallel to provide maximum tensile strength
What is the composition of ligaments?
What do they do?
Collagen fibres interspersed with fibroblasts
Less regularly arranged than tendons
Elastic ligaments are mainly composed of elastin
Connects bone to bone
What does a tendon do?
What is its composition?
Connects muscle to bone
Collagen fibres interspersed withflattened fibroblasts, fascicles (bundles of collagen and fibroblasts), seperated by endotendium (loose CT) and held together by peritendium.
A fibrous sheath surrounds the whole tendon
What are aponeuroses?
Flattened tendons
What is the make up of irregular dense connective tissue?
What is its function?
Interwoven bundlesof colagen
Small amount of reticular and elastic fibres
Counteracts multidirectional forces to which the tissues are subjected
Where is irregular dense connective tissue found?
Dermis of the skin, to withstand multidirectional forces and prevent tearing, elastic fibres allow a degree of stretch
Capsules of some organs
Large septa and trabeculae of many organs
Deep fascia of muscles
Periosteum
Preichondrium
Dura mater
What is heparin?
An anticoagulant
What i histamine and what does it do?s
Increases blood vessel wall permeability
Substance attracting neutrophils and eosinophils
Secretions for reactions
What are the two types of adipose tissue?
What are the functions of adipose?
White: single fat droplet in cells
Brown: seperate droplets
What are some disroders of connective tissue?
Systemic sclerosis: all organs have excessive accumulation of collage: fibrosis, hardening and functional impairment of skin, digestive tract, muscels, kidneys etc
Keloid: forms scars on skindue to abnormal amounts of collagen
Scurvy: vitamin D deficiencvcy, defective collagen synthesis as cofactor for prolyl hydroxylase. Degeneration of connective tissue, periodontal ligament affected, loosengng of teeth with loss, bleeding gums.
Marfan’s: defect in gene coding for fibrillin, which affects elastic fibres. Large elastic arteries like the aorta rupture due to bulging caused by a smaller lumen.
Ehlers danlos: deficiency in reticular fibres (type III collagen) causing rupture in tissues with high reticulin
What are types of variation in the macroscopic structure of human skin?
Colour: ehinicity, site (lips/areolae), UV exposure
Hair: site (palms, soles, lips have none), sex (more body hair in men),, age (male baldness, greying), ethinicity (colour, character)
Thickness
Laxity: site, age, UV exposure (injury to dermal collagen/elastin)
Oiliness: puberty, site
How do some variation in the macroscopic structure of skin influence the susceptiibility/ manifestations of some skin diseases?
VITILIGO (autoimmune depigmentation): less of a problem in fair skin, hardly noticeable. Psychosocial effects in dark skinned as obvious.
ALOPECIA AREATA/TOTALIS (autoimmune hair loss): More impact in women, psychosocial, especially if on scalp.
ACNE: common in puberty
UV INDUCED: more susceptible in fair skinned, to UV induced acute sunburn, freckling, ageing and skin cancer, especially if red hairded and blue eyed. No sunburn in blacks. Low basal cell carcinoma and malignant melanoma in blacks
What is the epidermis made of?
What are the different layers of the epidermis?
Stratified squamous keratinsied epithelium, made up mainly of keratinocytes and their products
4 layers
Horny layer: stratum corneum
Granular layer: stratum granulosum
Prickle cell layer: stratum spinosum
Basal layer: stratum basale
What is the process of keratinocyte differentiation in each of the 4 layers of the epidermis?
Keratinocyte mitosis mainly in the basal layer, the daugther cells then move up to the prickle cell layer.
In the prickle cell layer terminal differentiation begins and they lose the ability to divide. Keratinocytes synthesise keratins for strength. Joined by prickle like desmosomes.
In the granular layer they lose their plasma membrane and begin to differentiate into corneocytes. This layer contrains keratohyalin granulesm, which are aggregations of keratins, other fibrous proteins (filaggrin and involucrin) and enzymes which degrade membranes.
The horny layer is made up of layers of flattened corneocytes, highly keratinised squams, they have a major role in skin barrier function.
What are keratins?
What are they found in?
Heterodimeric fibrous proteins
Epidermis
Hair
Nails
What is the transit time of a keratinocyte from the basal layer to the horny layer?
30 to 40 days
What other epidermal cells are there besides keratinocytes?
What do they do and where are they found?
MELANOCYTES: dendritic cells of neural crest origin. Occur at invtervals along the basal layer. DIfficult to see without special stains. They produce melanin, the main skin pigment, more melanin is produced in dark skin.
LANGERHANS CELLS: dendritic cells of bone marrow origin. Scatted throughout the prickle cell layer. Difficult to see without special stain. Specialised capacity to present antigens to T lymphocytes and mediate immune reactions - allergic contact dermatitis
What are some disorders of the epidermis?
Psoriasis
Akkergic contact dermatitis
Malignant melanoma
Vitiligo
Describe psoriasis
A disorder of abnormal epidermal growth and differentiation
Common: 1 in 50 people
Cause is unknown, but runs in families
Autoimmune and T cell mediated
Extreme proliferation of epidermal basal layer, causing gross thickening of the prickle cell layer
Production of excessive stratum corneum
Clinically manifests as excessive scaling
Treat with immunosuppresant
Often causes psychosocial issues
Describe allergic contact dermatitis
Mediated by Langerhans cells
Present antigens to T lymphocytes
Often in response to nickel
Describe malignant melanoma
Aggressive neoplasm of melanocytes
Retention above basement membrane of epidermis is associated with good prognosis
More penetrating nodular melanomas have a poor prognosis
Common moles are benign growths of melanocytes, sometimes hard to distinguish from melanomas clinically
Describe vitiligo
Autoimmune attack of melanocytes
Causes depigmentation
Often symmetrical, may be due to neural control down to neural crest embryological origin of melanocytes
Much more visible in dark skin, psychosocial issues
What is alopecia areata?
Autoimmune attack of hair follicles
Describe the dermo-epidermal junction
Basement membrane below the basal layer of the epidermis
Best seen with a PAS stain: Period Acid Schiff
InterdigitatingB
asal cells connected by hemidesmosomes
What is the structure of the dermis?
Dense irregular connective tissue: spiindle shaped fibroblasts. ECM main constituent with mainly type 1 collagens and elastins
Blood vessels: small in the superficial dermis, large in deeper dermis.
Lymph vessels
Mast cells: arround blood vessels, histamine release in allergic reaction, leakage of plasma causing oedema.
Nerves: cutaenous sensory nerves transmit sensation
What is the main component of scar tissue?
Collagen
What causes birthmarks and port wine stains?
Birthmarks: malformation of blood vessels
Port wine stain: congenital malformation of blood vessels, always dilated
What is the result of damage to collagen and elastin?
Solar elastosis
Stretch marks: straie
Scars: keloids
What are examples of skin appendages?
Hair follicles and sebaceous glands: pilosebaceous unit
Sweat glands: eccrine/apocrine
Nails
Describe a pilosebaceous unit
Sebaceous gland feeds into the hair follicle, side of hair shaft
Sebaceous glands are a branched type of acinar gland
Holocrine secretion of sebum, cell distintegration
Arrector pili muscle for goosebumps
Large on face, produce lots of sebum, obstructed in acne- infection
Describe eccrine and apocrine sweat glands
ECCRINE: major sweat glands, found in skin and porduce clear odourless substance of water and NaCl which is reabsorbed in the duct. Active in thermoregulation, controlled by the hypothalamus. Composed of intraepidermal spiral duct, stright dermal portion and coiled acinar portion in the dermis
APOCRINE: large sweat glands, most abundant in axillae (underarms), genital and submammary areas. No function of value, produce odourless protein rich apocrine secretion. Digestion by cutaneous microbes produces odour.
What are the main functions of the skin?
Barrier function: stratum corneo prevents exogeneous absorption. Much studies as most be overcome by percutaneous absorption of drugs, can be disrupted in disorders like psoriasis (loss of fluid, protein, nutrients, heat. Excessive exogeneous absorption)
Sensation: sensory nerves allow sense of touch, temperature, tissue damage. Disrupted in leprosy (peripheral nerves disorder) and diabetic sensory neuropathy
Thermoregulation: vascular dilation leading to heat loss, contriction retains heat, gives pallor. Failure leads to serious consequences. Eccrine sweating, evaporation.
Psychosexual communication: manipulated as a means of communication and expression, tattoos and piercings
What are some properties and functions of cartilage?
Non-vascular, strong, pliable
Semi solid, firm, tough jelly
Support of organs, articulating surfaces of bones, greater part of the fetal skeleton
Describe the composition of cartilage generally
Originates from mesenchyme which differentiates into chrondorblasts, which secrete the matrix
The matrix surround and entraps these cells in lacunae, they are then referred to as chondrocytes
Isogenous clusters of cells
Ground substances made up of type I collagen, glycosaminoglycans, gproteoglycans
Lots of hyaluronic acid for resistance to pressure
No inorganic substances
Mesenchymal cells
What usually surrounds cartilage?
What type of connective tissue is this?
What are its layers?
Perichondrium
Dense irregular connective tissue
Couterfibrous layer, and inner cellular (CHONDROGENIC) layer with chondroblasts
How does cartilage develop in the embryo?
Cartilage first appear in the 5th week of development
Embryo skeleton composed of hyaline cartilage, until it is replaced by bone
Hyaline cartilage remains in the epiphyseal growth plates and articular cartilage
Describe where hyaline cartilage is found
Respiratory passages: C shaped cartilage
Articulating surfaces of long bones
Anterior ends of the ribs
Fetal skeleon
Nose
Epiphyseal growth plates
Describe the structure and function of hyaline cartilage
Matrix with proteoglycans, hyaluronic acid and type II collagen, bound to fine collagen matrix fibres
Has perichondrium except on articular surfaces
Avascular so must rely on diffusion for nutrient supply
Offers firm and flexible support
Only singular chondrocytes
Describe where elastic cartilage is found
Ear (pinna)
Eustachian tube
Epiglottis
Describe the structure and function of elastic cartilage
Matrix is like hyaline cartilage
With collagen and many elastic fibres
Has perichondrium and is avascular
Provides support and maintains the shape of structures
Gives extra flexibility, easier rebound
Describe where fibrocartilage is found
Intervertebral discs
Menisci of the knee
Pubic symphysis
Portions of the tendons
Temporomandibular joint
Sterno clavicular joint
Describe the structure and function of fibrocartilage
Matrix like hyaline cartilage
Abundant type I collagen in thick bundles
Gives support and rigidity, strongest cartilage
Very strong and resistant to stretching and compression, weight bearing
Cells in rows in isogenous groups
No perichondrium
What is an articular surface?
Where bones and joints meet
Describe how cartilage grows
Appositional growth inwards from the periphery, perichondrium
Deeper in cartilage, interstitial growth from isogenous groups
What clinical conditions can arise concerning hyaline cartilage?
Can calcify/ossify in old age and disease
Susceptible to degenerative aging process, which is normal but accelerates in aging via the calcification of matrix due to increase in size and number of chondrocytes and cell death
Joint pain can be the result of articular cartilage erosion at the ends of bones (osteoarthritis)
Rheumatoid arthritis occurs when secondary destruction occurss by granulating synovial membrane tissue, autoimmune
How does elastic cartilage differ from hyaline cartilage when an individual ages?
It does not calcify/ossify in old age
What clinical conditions can arise concerning fibrocartilage?
Rupture of annulus fibrosus (intevertebral disc capsule) leads to a slipped disc
Tearing of menisci
What are the characteristics of bone?
Hardest tissue in the bone: can withstand compression, stress and deformation
High vascular and well supplied with lymphatics and nerves (especially sensitive to pain in the periosteum)
Contains cells, fibres and ground substance (calcified matrix)
What are the main functions of bone?
Support
Protection
Mineral storage (calcium and phosphate)
Haemopoiesis
What are the two types of bone?
Spongey/cancellous/trabecular/medullar bone
Compact/dense/cortical bone
What is the structure of compact bone?
Hard, outer bone layer
80% of skeletal mass
Covered and lined by connective tissue, PERIOSTEUM, tough, vascular fibrous layer
Concentric lamellae with central neurovascular Haversian Canal, which communicate via Volkmann’s canals
Concentric circles are osteons
What is the structure of spongey bone?
Deep, porous, highly vascular
Meshwork of trabeculae filled with marrow, fine bony columns
No haversian or volkmann’s canals
Irregular lamellae remodelled by osteoblasts and osteoclasts
Osteocytes in lamellae
What is marrow made up of?
Red marrow: RBC synthesis
Yellow marrow: WBC synthesis
Marrow cavity is lined with a thin cellular layer: ENDOSTEUM
What is the difference in structure of immature and mature bone?
Immature bone: random arrangement of osteocytes - woven bone
Mature bone: osteocytes arranged in concentric lamallae of osteon. Reabsorption cancals parallel with long axis
What cells are found in bone?
Describe each type
Osteogenitor - OSTEOBLASTS: synthesise the organic components of bone, making bone. They produce the osteoid matrix.
OSTEOCYTES: found in lacunae cavities, maintaining bone. Trapped osteocytes. Slender cytoplasmic process, reach out to adjacent osteocytes via canaliculi. Nutrient transfer, also connect with central Haversian canal.
OSTEOCLASTS: large multinucleated cells from monocytes, which digest bone. Release H+ ions, lysosomal enzymes.
Describe the composition and properties of the bone matrix
65% inorganic, 35% organic
Calcium hydroxyapatite crystals, calcium phosphate, calcium carbonat
23% Type 1 collagen, 10% water, 2% non collagen proteins
Hardness and rigidity is due to interactions between calcium salts and collagen
Flexibility is due to collagen
What is the primary microstructure of bone - woven, immature bone
First bone to appear in development and repair, then replaced by mature bone
Collagen fibrils arranged randomly in an interwoven fashion
More cells and less minerals
What is the secondary microstructure of bone - lamellar, mature bone
Compact dense bone: series of haversian canals, osteon, consisting of concentric lamellae of bone laid around a central canal containin blood vessels
Spaces between Haversian systems are filled with bony lamellae (interstitial lamellae)
Outer surface has extended lamellae (circumferential)
Songey bone: meshwork of bone plates which are filled with marrow,. ALways surrounded by compact bone
Briefly explain endochondral ossification
Cartilage to bone
Cartilage is reabsorbeds and replaced with bone
Begins at the primary centre in the diaphysis
Later at each end at the seconday centre in the epiphyses
Growth in length is at the epiphyseal growth plates
Briefly explain how loose connective tissue or mesenchyme becomes bone
Intramembranous ossification
Bone begins as highly vascularised loose connective tissue
Mesenchymal cells differentiate to osteoblasts, surrounded by collagen fibres and ground substance
Secrete uncalcified osteoid and then become osteocytes
Briefly explain how bone is remodelled and repaired
ACtions of osteoblasts and osteoclasts
Release and incorporation of calcium into and from the matrix
what is a fracture?
Bleeding from multiple bleeding blood vesselsHa
emotoma between broken bone ends
Describe the cellular processes involved in bone repair following a fracture
Bone breaks, bone matrix is destroyed and bone cells adjoining the fracture will die
. Blood vessels in periosteum and bone break.
Haemtoma forms with fibrous tissue (PRE CALLUS or PRO CALLUS if periosteum is intact). Inflammatory cells invade to form this.
New blood vessels into haemotoma, collagen spans break, hyaline cartilage forms.
Osteoblsats start to reconstruct spngey bone, OSTEOCALLUS. Calcified to primary then secondary bone. New cancellous bone formed for about two months
Bone remodelled via tendons, mechanical stress. Osteoclasts. Mature bone forms
Bone heals without forming a scar
Describe 5 steps in healing of a fracture
Break
Haemotoma PRE/PRO CALLUS
Cartilage callus
Primary Bone
Secondary Bone
What are the three types of bone grafts used from bone banks?
AUTOGRAFT: donor is recipient, most successful
HOMOGRAFT: donor is different human, may be rejected as foreign
HETEROGRAFT: donor is of a different species, least successfulm although calf bone loses antigenicity with refridgeration
What are the two types of ossification?
Briefly explain the difference
Endochondral: from cartilage
Intramembranous: from mesenchyme or loose connective tissue sheet
Describe endochondral ossification
Bone formation in hyaline cartilage model, which is reabsorbed and replaced by bone = mineralised
Most bones formed in this way, long bones such as femur and humerus
STEPS: initial cartilage model, collar of periosteal bone in shaft
Central cartilage in diaphyses calcifies, nuterient artery penetrates, osteogenic cells. Primary ossification centre
medulla to cancellous bone. Secondary ossification centre at the epiphyses.
Epiphyses ossify and growth plates move further apart, increased length
Growth in diameter by depostion of bone at periphery of shaft, external modification by osteoblasts to create narrow diaphysis
Epiphyseal growth plates replaced by bone when growth stops, hyaline cartilage at articular surface
Where does intramembranous ossification occur?
Within condensations of mesenchyme
Flat bones: skull (parietal, occipital, temporal, frontal), maxilla, mandible, pelvis, clavicle
Also thickens long bone
Describe the process of intramembranous ossification
Bone development starts in highly vascularised connective tissue e.g. flat skull bones
Focus of activity is primary ossification centre
Mesenchymal cells differentiate into osteoblasts, surrounded by collagen fibres and ground substance
Osteoblasts secrete osteoid which later calcifieds
Osteoblasts become osteocytes, embedded in osteoidMineral depostis in trabeculae radiate outwards from POC
How is compact bone formed?
Initially spongey bone is formed
Later transformed to compact
Structure changes constantly by remoedelling
Describe osteogenesis imperfecta (brittle bones)
Group of rare genetic disorders, affecting synthesis of type I collagen by osteoblasts and fibroblasts
Weaknesses in structure which rely on collagen for strength: sclearae, skin, tendons, ears, skeleton, teeth, joints
Various types: one of which is lethal before birth.
Multiple fractures, bone deformities due to weak callus, bowing of bones, thin bones, some have blue sclearae
Medicolegal importance as multiple fractures can be confused with deliberate injury = abuse
Decribe osteoporosis
Loss of bone mass as age increases, reduced so there is a increased risk of fracture, as no longer provides adequate mechanical support
Osteoclasts> osteoblasts. Inadequate filling of osteoclasts resorption bays
Risk areas: neck of femur, vertebral column, distal radius
2 types: Type 1 post menopausal due to loss of osteoclast inhibition by oestrogen. Type 2 senile, after age 70, lss of osteoblast function
Risk factors: insufficient calcium intake, insufficient vitamin D, lack of physical activity, cigarette smoking, being female, genetic, blacks have high bone mass peak
Describe the consequences of vitamin D and calcium deficiency on bone
Needed for normal ossification, promotes mineralisation of bone
Rickets in children: bone matrix does not calcify normally, epiphyseal plate distorted by strains of body weight, bones grow slowly and become deformed. Pliable osteoid, bendy bones, fractures. Bowing of femur, enlarged chostochondral rib junctions, bossing of skull.
Osteomalacia in adults: softening of bones. Deficient calcifcation of recently formed bone, partial decalcification of older matrix, causing fragility anf increased risk of fractures. Bone pain, back ache, muscle weakness
Explain the importance of vitamin D in normal bone development
Both dietary and skin synthesised, essential for normal ossification
As involved in calcium and phosphate absorption in small intestine
In its absence, bone is poorly mineralised, a pliable matrix called osteoid (uncalcified, secreted by osteoblasts)
Affected bones can’t support weight and bend.
Common cause of osteomalacia
Hoow can osteomalacia be prevented?
Adequate intake of calcium, vitamin D and phosphate
Adequate sun exposure (especially in dark skinned individuals)
Outline the cause and features of achondroplasia
Congential and often hereditary skeletal disorder, caused by failure of proliferation and column formation of epiphyseal cartilage cells
Defect in endochondral bone formation impirs longitudinal growth of the tubular bones, short limbs
Skull unaffected as formed by intramembranous ossification
Autosomal dominant, gain of function in fibroblast growth factor, increased proliferation of chondrocytes in growth plates, less matrix
Epiphyseal growth plates are thin, few cells in the proliferating zone, hypertrophic cartilge cells form irregular columsn, zone of provisional calcified cartilage is smalll and does not provide adequate scaffolding for bone matrix depostion by metaphyseal osteoblasts
What is the effect of growth hormone on bone??
Lack and excess
Lack of GH affects epiphyseal cartilage causing pituitary dwarfism if before puberty. After, no effect, no growth plates in epiphyses
Excess before pubery, excess long bone growth, gigantism. In an adult, periosteal growth, acromegaly. Usu
ally due to benign anterior pituitary tumour
What is the effect of sex hormones on bone?
Influence time and appearance of ossification centres
Precocious sexual maturity close epiphyseal growth plates prematurely retarding bone growth
Sex hormone deficiencies delay plate closure causing tall statuere, later puberty.
Androgens and oestrogens influence pubertal growth spurt.
What is the effect of thyroid hormone deficiency on bone?
In newborn hypothyroidism causes cretinism
Stunted physical and mental development
Short stature
What are the three types of muscle?
Striated: cardiac and skeletal
Non striated: smooth
What is the banding structure of muscle?
MHAZI
M line is in the H band, which is in the A band
Z line is in the I band
Describe actin and myosin simply, and where they are
Thin filament is ACTIN, mainly in I band
Thick filament is MYOSIN, mainly in A band so H and M too
What is a sarcomere?
Z line to Z line distance
What forms the thin filaments in skeletal and cardiac muscle?
Actin and tropomyosin molecules wrap around each other
Troponin complex attached to each tropomyosin molecule, covering the binding sites for the myosin filament
TnI binds to Actin
TnC binds to clcium
TnT binds to tropomyosin
What makes up the thick filament?
Many myosin molecules
Heads protrude at opposite endsCent
Centre of sarcomere is devoid of heads
Describe the sliding filament theory of muscle contraction
A band length is constand
Length of the H and I bands decrease
Actin filaments move in to overlap with myosin
Describe the sarcotubular system of skeletal muscle
AI junction, one transverse (T) tubule
T tubule extends from sarcolemma
2 terminal cisternae per tubule, TRIAD
Explain the mechanism of the sliding filament model of muscle contraction
Troposmyosin blocks actin binding site for myosin. Calcium ions bind to TnC, moving tropomyosin away, allowing myosin heads to bind actin and begin contraction.
- Myosin head is tightly bound to actin in rigor conformation. Lack of ATP.
- ATP binds to the myosin head causing it to uncouple from actin.
- Hydrolysis of ATP causes uncoupled myosin head to bend and advance 5nm
- Myosin head binds weakly to actin releasing Pi, causing power stroke. in which myosin head returns to former position. Actin moves to M line, binds to myosin head tightly again.
Myosin heads attach at different times causing movement
Describe the mechanism of muscle innervatio and excitation contraction coupling
ACtion potential at presynaptic neron terminal, calcium infklux from ECF to ICF
Influx causes presynaptic vesicles to release ACh in synaptic cleft
ACh binds to nicotinic acetyl choline receptors bound to motor end plate, ligand gated ion channels open allowing sodium ions to diffuse in, depolarising the sarcolemma, spreading to the T tubules
Voltage senor proteins of T tubule membrane change their conformation. Gated calcium ion release channels in adjacent terminal cisternae of SR are activated by this
Rapid release of calcium into sarcoplasm
Calcium binds to TnC, initiating the contraction cycle
Calcium ions return to the terminal cisternae of the SR
Describe the structure of skeletal mucl from the epimysium to the muscle fibres
Epimysium: thick connective tisssue around muscle, sheath
Perimysium: around fascicles, a group of fibres, carries nerves and blood vessels
Endomysium: surrounds individual muscle fibresIn
Interdigitation of muscle fibres with surrounding connective tissue such as tendon at myotendonous junction - sarcolemma always between collagen bundles and muscle fibres microfilaments
What connective tissue is associated with skeletal muscle?
Tendons connect muscle to bone
Aponeuroses: muscle to bone or adjoining structures, flat and broad
Layers of dense connective tissue bind muscles into functional groups, DEEP FASCIA. Contain large blood vessels, nerves, and some fat.
What are muscle fibres (cells) composed of?
Myofibrils, which are composed of myofilaments, actin and myosin
Sarcolemma
Mitochondria
Nucleus
How do the A band and I band of skeletal muscle appear under a microscope?
A is dark
I is light
How are skeletal muscle cells formed?
Derived from the mesoderm, from multipotent myogenic stem cells
Give rise to myoblasts, which fuse to form a primary myotube, a chain of multiple central nuclei
The nuclei are displaced to the cell periphery by myosin and actin filaments
Describe the features of red muscle
Would fnid lots in a marathon runner
Smaller
Rich vascularisation
Rich myoglobin
Numerous mitochondria
Slow, weak contraction
SLow fatigue
Rich in oxidative enzymes, poor in ATP ase
Few neuromuscular junctions
Describe the features of white muscle
Wider
Poor vascularisation
Little myoglobin
Few mitochondria
Fast, strong contraction
Rapid fatigue
Poor in oxidative enzymes, rich in ATPase
More NM junctions
Describe the main features of skeletal muscle?
Long fibres, cylindrical
Many peripheral nuclei
Fascicle bundles, tendon connect to bone
Somatic neuronal voluntary control
Rapid forceful contraction
Striated
Describe the main features of cardiac muscle
Short branched cylindrical fibres
Single central nucleus, 1 or 2
Striated
Adherens type junctions join cells end to end, anchor cells and provide achorage for actin
Gap junctions for electrical coupling with adjacent cells, intercalated discs, Z bands
Intrinsic rhythm, involuntary, autonomic
Life long variable rhythm
T tubules on Z disc
SR less developed, diad not triad
Descibr the main features of smooth muscle cells
Spindle shaped with tapering ends
Central single nucleus
Gap and desmosome type junctions
Not striated, no sarcomeres or T tubules
Contraction still actin myosin based
Slower more sustained contraction, longer
Involuntary, autonomic, local stimuli
Form sheets, bundles or layers
Thick and thin filmaents are arranged diagonally, spiralling down the long axis for a twisting contraction
What is the term to describe the spontaneous and rhythmic contractile capabilites of the heart?
What sort of cells transmit action potentials from the atrioventricular node to the ventrical walls?
Myogenic
Purkinje fibres
Describe the microscopic structure of a cardiac muscle cell
T tubules on Z disc
Sarcoplasmic reticulum less developed
Diad not triad
Describe the conduction of the action potential in cariac muscle
Describe how purkinje fibres are involved
Action potential in sino atrial node
To atrioventricular node
Carried to ventricles by purkinje fibres by rapid conduction, enabling the ventricles to contract in a synchronous manner
Describe the structure of purkinje fibres
Large cells, modified monocytes
ABundant glycogen
Sparse myofilaments
Extensive gap junction sites
Compare the regenerative capabilities of the three muscle types
SKELETAL: cells can not divide by tissue can regenetate by mitotic activity of satellite cells, so that hyperplasia follow muscle injury. Satellite cells fused with existing muscle cells to increase mass, hypertrophy. Gross damage repaired by connective tissue leaving a scar. If nerve or blood supply is interrupted, muscle fibres degenerate and are replaced by fibrous tissues
CARDIAC: incapable of regeneration, following damage, fibroblasts invade and divide, laying down scar tissue
SMOOTH MUSCLE: reatin mitotic capabilities, can form new smooth muscle cells. Evident in pregnant uterus, muscle wall becomes thicker with hypertrophy and hyperplasia of individual cells
Where is smooth muscle found?
How is it innervated?
Found in contractile walls of cavities, passageways, vasculature, gut, airways, genitourinary, uterus, ducts, glands, iris
Innervated by autonomic, unmyelinated nerves
What is the clinical significance of smooth muscle?
How can smooth muscle be modified for different functions?
Hypertension, dysmenorrhoea, asthma, atherosclerosis
Modified in myoepithelial cells in acini of gland, myofibroblasts producing collagen and contract
Explain the use of troponin assays
TnI and TnT are useful markers
Cardiac ischaemi
Release in one hour
Must measure within 20 hours
Smallest change in troponin is MI
How often are contractile proteins replaced in skeletal muscle?
Every 2 weeks
What is atrophy?
What problems can it cause and how does it arise?
Wasting of muscle due to lack of use, in the aged, loss of nerve supply following injury. Muscle cell shrinks in size.
Disuse atrophy: maintenance requires frequent movement against resistance or fibres shrink and weaken
Loss of protein so reduced fibre diameter, loss of power
More atrophy with age
Destruction is greater than replacement of myofibrils
Can also be caused by denervation
Describe how atrophy occurs with age
Above the age of 30, muscle mass decreases
50% loss of muscle by age 80
Important in temperature regulation, so loss of non shivering thermogenesis
What are the general functions of skeletal muscle?
Movement
Posture
Stability of joints
Heat generation
How does muscle atrophy occur due to denervation?
Muscle no longer receives contractile signals which are required to maintain normal size
Indications of lower motorneurone lesions include: weakness, flaccidity, muscle atrophy with fasciculatations (spontaenous twitiching of small groups of muscle fibres), and degeneration of muscle fibres 10 to 14 days after injury.
Reinnervation within 3 months for good recovery, completely lost after 2 years
Muscle fibres are replaced with fibrous and fatty tissue which requires daily stretching as it causes shortening
What occurs in hypertrophy of skeletal muscle?
Replacement of fibrils is greater than destruction
Increase in muscle mass from work performed against load leads to
More contractile proteins, increase in fibre diameter
Metabolic changes: enzyme activity for glycolysis, mitochondria, stored glycogen, blood flow
Increased muscle length, addition of sarcomeres
Outline the physiology of the neuromuscular junction
Motor neurone synaptic knob releases acetyle choline into synapse as a result of calcium influx
ACh binds to nicotinic receptor on folded end plate region
Sodium ion channel opens, action potential down T tubules
Causes calcium ion release from SR, muscle contraction
Only 25% of ACh receptors need filling for a contraction
What is ACh terminated by?
At high motor neurone firing rates, what happens?
ACh is terminated by acetylcholinesterase
ACh release decreases at high neurone firing rates
Describe the pathophysiology of myasthenia gravis
Automimmune destruction of the end plate ACh receptors
and loss of end plate junctional folds
Widening of the synaptic cleft
Describe the symptoms of myasthenia gravis and when the crisis point occurs
Fatigability and sudden falling due to reduced ACh release, muscle relaxes
Drooping eyelids
Double vision
Affected by general state of health and emotion
Test: hold out arm when sat down, see if it collapses quickly
Crisis when it affects respiratory muscles
How is myasthenia gravis treated?
Acetylcholinesterase inhibitors
Stops it beraking down ACh
Neostigmine, physostigmine
Also can place eyes on the eyelids to decrease acetylcholinesterase activity
How is neuromuscular transmission affected in botulism?
Toxins block ACh release
Clostridium botulinium bacteria in soill
Can not breath properly
Used in botox
How is neuromuscular transmission affected in organophosphate poisoning?
Inhibits acetylcholinesterase irreversibly
ACh remains in the receptors
Muscle stays contracted
What are muscular dystrophies?
Genetic disorders group
Progressive muscle wasting and weakness
Failure of body to produce proteins, or not enough, in the muscle cell membrane
What is dystrophin?
Long rod shaped protein
Anchors sarcolemma to actin and myosin fibrils
Describe the pathophysiology of duchenne muscular dystrophy
Complete absence of dystrophin
Actin not anchored to sarcolemma, so fibres tear themselves apart on contraction
Creatine kinase liberated into serum
Calcium enters cell causing necrosis
Pseudohypertrophy (swelling), before fat and connective tissue replace muscle fibres
Describe the symptoms of duchenne muscular dystrophy
Describe some possible treatments
Early onset, Gower’s sign, push hands on knees to push strength up
Slow, late walking, falls
Contractures: stiff joints. Imbalance between agonist and antagonist muscles
Steroids: prednisolone, helps to build up muscle fibres
Genetic reseatch, to make dystrophin with stem cells, gene therapy.
Ataluren drug trials, ribosomal interaction to make dystrophin
Give examples of myopathies
Inflammatory: poliomyostitis (chronic inflammation, viral/autoimmune), myalgia (muscle pain) and influenza
Electrolyte imbalances: cramps, diuretic therapy (hypokalaemia)
Thyrotoxicosis: increased BMR and protein catabolism
Hypoparathyroidism: hypocalcaemia causing tetany
Channelopathies: malignant hyperthermia
Describe the pathophysiology of malignant hyperthermia
Rare, autosomal dominant condition, life threatening reaction to some general anaesthetics
Volatile anaesthetic agens and NM blocking agent succinylcholine, which is a non competitive inhibitor of ACh on muscle nicotinic receptors. It is degraded by butyrlcholinesterase much more slowly than ACh by acetylcholinersterase
Uncontrolled increase in calcium release in the muscle, and uncontrolled increase in oxidative metabolism, overwhelming body’s capactiy to supply o”, remove co2 and regulate body metabolism. Heat production, circulatory collapse and death.
Can be treated with dantrolene a muscle relaxant
How are nerve fibres structured outside the CNS?
Bound together by connective tissue
To form the peripheral nerves
What are fibres that carry impulses towards the CNS called?
Afferent or sensory fibres
What are fibres that carry impulses away from the CNS called?
Motor or efferent fibres
What is an entire nerve sheathed by?
Epineurium
What is a nerve fascicle ensheathed by?
And what travels in this? What is the clinical relevance?
Perineurium
Point where blood vessels travel within the nerve
Potential malignancy transport
What is a single nerve axon ensheathed by?
Endoneurium
Describe the structure of a neuron
All neurones have one axon
Cell body with or without dendrites
Myelinated or unmyelinated
Axonal terminal
Describe the basic neuron types
Multi polar: multiple dendrites, one axon, motoneuron
Bipolar: one dendrite and one axon, interneuron, rare, in retina of eye
Unipolar/ pseudounipolar: no dendrites, one axon, sensory neuron
Describe how peripheral nerves are myelinated
Sleeve of Schwanna cells, the neurolemma
Wound in several concentric layers
Discntionous, with gaps called nodes of ranvier
To increase the speed of conduction, correlates to level of axonal myelination
How are myelin sheaths histologically processed?
Myelin is mainly lipid, so poorly preserved in routin processing techniques
Special fixatives and stains
Osmium tetroxide
How are axons myelinated in the CNS?
Glial cells called oligodendrocytes
Produce and maintain the myelin coating
Covering up to 250 axons
Describe the myelination in the autonomic and somatic nervous systems
Autonomic (involuntary): myelinated (CNS) and unmyelinated (PNS) neurones
Somatic (voluntary): all myelinated neurones for faster action potentials
What neurotransmitters do excitatory neurones use?
What to they do to the next neuron?
Glutatmate/aspartate
Depolarise next neuron
What neurotransmitters to inhibitroy neurones use?
What do they do to the following neuron?
Glycine or GABA (g amino butyric acid)
hyperpolarises the next neuron
What causes neurotranmitters to be released?
What is the neuron proximal to the synapse called?
What is the neuron distal to the synapse called?
Pre synaptic is proximal
Post synaptic is distal
How does demyelination cause a slowing of conduction veloctiry within a nerve?
Impulse has further to travel as saltatory propagation is inhibitied, slower response
EG Multiple Sclerosis
Describe multiple sclerosis
The myelin sheath is destructively removed from the axon and replaced by scar tissueOligodendrocytes and axons can also be damaged
Condction velocity and saltatory propagation is impaired
Scar tissue does not permit conduiction therefore the axon is useless
Describe the structure of a nerve cell body (perikaryon)
Engine of neurone, 4 to 120 micrometres in diameter
Varies in shape, may have dendrites, axonal hillock last site of summation
Nissl substane, aggregration of RER for protein synthesis
Golgi packages neurotransmitters into vesicle
Describe dendrites
Specialisations to increase cell body surface area
From cell body, proximal, further away, distal
Dendritic tree
Dendritic spines for learning experiences, Down’s can’t express
Does not matter where the signal is received, it is maintained
Describe the variety of connections between neurones
Lightly (one cell to one cell)
to heavily (one nerve cell to thousands)
How many pairs of spinal/segmental nerves are there?
31
What s the nervous system made up of?
What are nerves from the brain called?
Brain, spinal cord and nerves
Cranial nerves
How is the central nervous system encased?
3 layers of connective tissue
Meninges
What are the 3 meninges, from outside to inside?
Dura Mater
Arachnoid Mater
Pia Mater
What is CSF?
Cerebrospinal fluid
Equivalent to arterial and venous fluid of the CNS
Formed by choroid plexus of arteries
Butrition and oxygenation of CNS neurones, carries away metabolites
What are the clinical implications of too much CSF?
Brain death
High hydrostatic pressure
What are the leptomeninges?
Arachnoid mater and pia mater
What is the sub arachnoid space?
The space between the pia mater and arachnoid mater
What is within the subarachnoid space?
How does it arise?
Cerebral spial fluid flows here, and blood vessels
Dilations occur floowing failures of arachnoid mater to follow brain furrows, and adher to pia mater
Dilations are CSF cisterns
Important clinically to confine brain bleeds
What are the two major cell types in the CNS?
Neurons, functional 10%
Glial cells, make sure neurones thrive, 90%
What is the function of glial cells generally?
Support neurones, help maintain homeostasis, form myelin, insulate neurones, destroy pathogens
What are various glial cell types?
What are their functions?
Where are they found?
Astrocytes: blood brain barrier, assist in transfer of nutrients and waste, in the CNS
Oligodendrocytes: myeliantion, up to 250 axons per cell, in CNS
Microglia: immune and inflammatory reactions, macrophages, in CNS and PNS
Schwann cell: myelination, many cells per axon, in PNS
Satellite cells: physical support of peripheral neurones (afferent and efferent), PNS
What are the types of input summation?
+ excitatory
- inhibitory
SPATIAL: summated with respect to spatial location on cell
Temporal: summated with respect to time of arrival on cell body
What are the functions of an axon?
Summates all inputs to the neuron
Initiates action potentials
Conducts action potentialsm away from the cell body to the terminals
Depolarisation of terminals leads to release of neurotransmitters
Communicates with follower cell
What are the functional classes of neurone? Explain each
Sensory, pseudounipolar: receptros that transduce to electrical impulses
. Conduct to cell body, then spinal cord/brain
, some are fastest conducting neurones in body, AFFERENTS
Motor, multipolar: carry out brain instructions to move muscles, conduct from brain to muscle, largest neurones, integrate large array of inputs to one output, clinically very important. EFFERENTS
Inter, multipolar: 95% of nervous system, smallest, wholly in CNS, info relays between sensory and motor neurones, probably most complex neurones in the body. RELAYS
Describe the cell membranes of neurones
Bilipid, selectively permeable to certain ionic species.
Development of ionic concentration gradients between inside and outside of cells.
ELECTROCHEMICAL GRADIENT
Makes the neurone electrically charged
How are ion channels gates on neurones?
Voltage gates: opened or closed by voltage changes
Others opened by nurotransmitters: ligand gated
What value is the neuron hyperpolarised at? resting potential
-70mV
Describe the charges of the neuron at rest
Net negartive inside, net negative outside
Active transport of Na+/K+ pumps
More sodium out, potassium in 3:2, potassium can get back out, sodium can’t get back in
Describe how an action potential is generated?
Stimulus above threshold -55mV, causes Na+ channels to open, Na+ flows back in, membrane is depolarised, local area positive
Depolarisation moves along membrane
After actional potential, K+ channels open, flow out and restore the resting potential
Goes too far: refractory period
What is a ganglion?
Accumulation of nerve cell bodies outside the CNS
Afferent cell bodies are in the spinal or cerebral ganglia in the dorsal root of spinal nerves
What is the autonomic nervous system?
The involuntary nervous system
What are the two main divisions of the autonomic nervous system?
Sympathetic
Parasympathetic
TheANS is comprised of a series of how many neurones?
Describe
Series of 2 neurone, pre-ganglionic and post-ganglionic
1 cell has a cell body in the CNS, the other cell has a cell body in the PNS
What to ANS neurones exert actions on?
Viscera
Smooth muscle
Secretory glands
What is grey matter?
What is white matter?
What is in the central canal?
What is used to stain a TS spinal cord?
Grey matter: neuronal cell bodies
White matter: neuronal axons
CSF in the central canal
Cresyl violet stain
In the CNS, what is the name for collections of:
Neuronal cell bodies?
Neuronal axons?
Nuclei
Fibre tracts
In the PNS, what is the name for collections of:
Neuronal cell bodies?
Neuronal axons?
Ganglia
Nerves
How is the nervous system divided into different levels and areas?
CNS and PNS
to Afferent and Efferent
Efferent to Somatic and Autonomic
Autonomic to Sympathetic, Parasympathetic and Enteric
Describe somatic efferents
Voluntary
Simplest possible layout
1 neurone carries output, terminates directly on effector organs
Activate when needed, otherwise inactive
Efferents undeveloped at birth, fully developed at puberty
What are the functions of the autonomic nervous system?
Fundamental life functions, non stop
Balance of opposing systems, sympathetic and parasympathetic
Maintains constant homeostasis
Promotes excretory mechanisms intermittently
Describe autonomic innervation
Most innervated by ANS dually, PNS and SNS
Dominance of each depends
Exception: sweat = SNS only
What happens when the sympathetic or parasympathetic nervous systems are overactive?
SNS overactive: constriction of blood vessels (oreserve heat)
, shortage of substrate to body tissues
PNS overactive: dilated blood vessels, shortage of substrate to brain
Describe CNS and PNS neurones in the autonomic nervouse system
CNS: pre-ganglionic, myelinated, white rami communicantes
PNS: post-ganglionic, not myelinated, Grey rami communicantes
What is the main function of the sympathetic nervous system?
Involved in the fight/flight/fright response
Expressed mainly in stress situations
Diversion of blood to muscles and heart, increase in heart rate, increase in blood pressure, reduced blood floow to GIT and skin, pale, hyperventilation.
Describe the outflow of the sympathetic nervous system
Thoraco-Lumbar
Nerve fibres have cell bodies in all 12 thoracic sections, and first 2 lumbar sections
Dorsal, LATERAL and ventral horns in TS spinal cord
Describe the two nerve fibres of the sympathic nervous system and their synapsing
Short pre ganglionic, long post ganglionic
Paravertabral chain of ganglia along sympathetic trunk, parallel to vertebrae, skull to sacrum
May synapse at same levels as origin (paravertebral origin)
May synapse a different level to origin
May not synapse in the paravertebral chain (splanchnic nerves)
Describe the neurotransmitters and receptors in the sympathetic nervous system
Preganglionic neurones are CHOLINERGENIC (Acetylcholine)
So post ganglionic receptors are NICOTINIC
Post ganglionic receptors are NORADRENERGENIC (noradrenaline)
Two classes of adrenoreceptors: alpha 1 and 2, and b 1 and 2
Exceptions: some synapses are cholinergenic, perspiration and ejaculation pathways
In the ejaculation pathway, which division of the ANS is responsible for
erection?
ejaculation?
Erection: Parasympathetic POINT
Ejaculation: Sympathetic SHOOT
What are the main functions of the parasympathetic nervous system?
BASAL, relaxation, calm
Reduced heart rate and force of contraction
Promotes digetion
Promotes bodily functions such as bladder emptying
Promotes sleep
Describe the outflow of the parasympathetic nervous system
Cranio sacral outflow
Describe the two nerve fibres of the parasympathetic nervous system
Long pre ganglionic
Short post ganglionic
Post ganglionic neurones in walls of effector organs
Describe the neurotransmitters and receptors in the parasympathetic nervous system
Pre ganglionic neurones are CHOLINERGENIC (acetyl choline)
Post ganglionic receptors are NICOTINIC
Post ganglionic neurones are CHOLINERGENIC
Effector organs are MUSCARINIC
How can neurotransmitters be exploited in the therapeutic domain?
Agonist (triggers response) and antagonists (block agonists)
Beta blockers in heart stop sympathetic stimulation
What are blood cells initially produced by in the foetus?
Mesoderm of the yolk sac
Liver
Spleen
Bone marrow
What is haemopoeisis?
The production of red and white blood cells, and platelets
Describe the process of haemopoeisis
PROLIFERATION:stem cell divides into 2, one replaces the original step cell (self renewal) and the other cell differentiates
DIFFERENTIATION: Haemopoetic progenitor will first differentiate to form either a myeloid blast (RBC, WBC, platelets) or a lymphoid blast (immunoresponse cells)
The progenitor will differentiate into a certain cell type under the influence of a particular cytokine
What is a cytokine?
Give some examples
A hormone, signalling molecule
Some types cause differentiation of blood cells
Erythropoietin: RBCs when pO2 is low
Thrombopoeitin: platelets
G-CSF, GMCSF, IL-6: colony stimulating factors
How many types of white blood cell are there?
Where do they circulate?
5 types
Blood and lymphatic systems
Where do T cells mature?
Thymus
Describe Neutrophils
Multilobed nucleus, small granules in cytoplasm (polymorphonuclear granulocyte)
Most common circulating WBCs, inactive in circulation, 10 hour lifespan
Migrate out to site of infection CHEMOTAXIS
PHAGOCYTOSIS
G-CSF (granulocyte CSF) increases production
Describe eosinophils
Bi lobed nucleus, large granules (polymorphonuclear granulocytes)
PHAGOCYTOSIS, of antigen antibody complexes, releases cytotoxic particles
Hypersensitivity reactions
Lifespan 8 to 12 days
Migration to serosa
Describe basophils
Quite rare, bi or tri lobed nucleus, dense granules, polymorphonuclear granulocytes
Mediate acute inflammatory reactions with histamin and heparin: oedema
Also hyaluronic acid and seratonin
Half life 2.5 days
Describe monocytes
Large kidney shaped single nucleus, mononuclear cells, no granules
Migrate to tissues to become macrophages
PHAGOCYTOSIS, interact with T cells, CHEMOTAXIS
DIAPEDESIS: intact through capillaries
Response to inflammatio and antigenic stimuli
Describe lymphocytes
Large deep staining nucleus, mononuclear cells
B: humoral immunity, stimulated by antigens, transform to plasma cells, secrete immunoglobulins, antibody forming
T: express CD4 on surface (helper), can be killer cells, permit transformation of B cells into plasma cells, CD8+ suppressor cells. Mature in thymus
Natural killer cells too
Describe the structure of erythrocytes
8 micrometre diameter
, biconcave disc
Carries haemoglobin, 4 globin chains, 2 alpha, 2 beta, each with a haem group
Spectrin and actin affect shape
Membrane with glycoproteins and antigens
If changes in shape, congenital or acquired, removed by spleen
What is the lifespan of a red blood cell?
120 days
What is the function of an erythrocyte?
Carrie oxygen to the tissues from the lungs, and carbon dioxide to the lungs
Maintains osmotic eqbrm of the circulation
Generates ATP from glucose making lactate
Flexible to pass through narrow capillaries
Provides oxygen when low, increase RBC production in response to hypoxia
What are the two main metabolic pathways in RBCs?
Glucose to lactate and ATP, glycolysis and lactate dehydrogenase
Hexosemonophophate - G6P to ribose sugars by glucose 6 phosphate dehydrogenase to generate NADPH
Describe haem catabolism
RBCs broken down in spleen, Hb to Haem
The iron is conserved
Unconjugated bilirubin yellow
Bilirubin conjugated in the liver, more watersoluble with glucaronic acid, less toxic
Liver to kidney, urobilinogen, yellow
Liver, gall bladder, in bile through bile duct, into intestines stercobilin, brown, egested
What does bilirubin in the blood cause?
Yellow colour, in the skin and sclearae
Bilirubin produced when prophyrin opens up
Toxic
Attaches to albumin as not very water soluble
Describe the structure and fucntion of reticular cells
Synthesise reticular fibres and surround them with cytoplasm
Type of fibroblast, type III collagen
Direct T and B lymphocytes to specific regions with the lymphatic tissues
What is the structure of platelets?
How are they formed?
Small round blue particles
Cell fragments, stored in the spleen
Produced from megakaryocytes in the bone marrow
Complex surface membrane
Alpha granules with fibrinogen and von Willebrand’s factor
Dense granules with ADP and calcium ions
What is a reticulocyte?
An immature RBC
What is the function of platelets?
Adhesion to damaged cell walls and aggregate together
Provides phospholipid surface as a binding site for clotting factors in the cascade
Aggregation: release of ADP from granules, glycoprotein receptors exposed
Interacts with factors VII, IX and X
Fibrin mesh traps platelets and RBCs
What does the bone marrow do?
Where is it found?
Produces RBCs, platelets and WBCs
Extensive bone marrow in infant
More limited in adult, mainly pelvis, sternum, skull, ribs and vertebrae
Blood cells released into sinusoids then the blood stream
What is the reticuloendothelial system?
Part of the immune system, containing phagocytic cells:
Monocytes, kupffer cells, macrophages, tissue histiocytes, microglial cells
Cells of RES identify and mount an appropriate immune resposne to antigens
Main organs: spleen, liver and LN
What are the types of T cells?
CD4 helper cells
CD8 suppressor cells
Describe the components of the innate humoral immune system
Transferrin and lactoferrin, deprive microorganisms of iron
Interferons, inhibit viral replication
Lysozyme, breaks down petptidoglycan in cell walls of bacteria
Antimicrobial peptides
Fibronectin: opposes bacteria and promotes their phagocytosis
Complemet: causes microbe destruction directly with or without phagocytic help
TNF a: suppresses viral replication and activates phagocytes
Describe the cellular components of the innate immune system
Macrophages/monocytes: phagocytosis and antigen presentation to lymphocytes
Neytrophils: phagocytic and antibacterial
Eosinophils: anti parasite and allergic respoinse
Basophils and mast cells, allergic response
Natural killer cells, recognise and kill abnormal cells such as tumours
Describe the humoural components of the adaptive immune system
Cytokines: promote differentation and proliferation of lymphocytes
Perforin: released by T killer cells to destroy cell walls
Antibodies: protect host by neutralisation, prevents binding to epithelia, opsonisation and complement activation
Describe the cellular components of the adaptive immune system
T cells: T helpers which become activated when CD4 binds to a specific antigen on MHC/antigen complex of an antigen presenting cell. Once activated, it clones itself to form active T helper cells and T memory cells
T killer, releases perforin when cell is already infected
B cells: divide to form plasma cells and memory cells when activated by a T helper, and release cytokines. Plasma cells produce specific immunoglobulins for a non self antigen
What are the roles of proteins in pathogens?
Nutrient acquisition
Reproduction
Respiration
Locomotion
How is the immune system alerted to damage?
By causing damage, breaking barriers to prosperous regions
Detect differences in proteins, different amino acid sequences
What does epithelial tissue do as the first barrier to pathogens?
Innate immune system
Adaptations to clear pathogens from the surface, cilia, regeration, tears, nasal hairs, coughin, enzymes etc
Natural antibiotics
Cytokines
Chemokines (attracts other cells)
When pathogens break through, endothelium is leaky to let cells out, phagocytosis, opsonisation
What is opsonisation?
Pathogen marked for ingestion and destruction by phagocyte
Describe the features of the innate immune system
Present from birth
Non specific
Not enhanced by second exposure
No memory
Poorly effective without adaptive response
Cellular and humoral
Triggers and amplifies adaptive response
Importance shown by rarity of innate inherited disorders
Describe features of the adaptive immune system
Arises from exposure to microorganisms
Specific pathogen immunity
Enhanced by second exposure
Acquires memory (memory cells)
Poorly effective without innate immunity
Cellular and humoral
Antibodies reflect infections to which they have been exposed, diagnostic tool
When do the innate and adaptive immune systems start to work?
Innate: immediate, quicker to respond
Adaptive: slower to respond, multiplication of cells, but lasts much longer after infection
What happens if innate or adaptive immune systems are lacking?
Innate lacking: does not respond well at all, microbes quickly multiply
Adaptive lacking: innate initially responds, then microbes proliferate
