Tissues Flashcards
What happens in the nucleolus?
Ribosomal subunits are synthesised
What three types of filament constitute the cytoskeleton?
Microtubules
Intermediate Filaments
Microfilaments
What are microtubules made of and what is the diameter of a microtubule?
Alpha and beta tubulin
20nm
What are microtubules used for?
Movement of organelles through the cell – involves motor proteins
Involved in spindle fibre formation
Describe the organisation of microtubules in cells.
They originate from a point within the cell called the microtubule organising centre (MTOC)
Microtubules are an important structural component for which cellular features?
Cilia and flagellae
Which component of the cytoskeleton distinguished different cell types?
Intermediate Filaments – different for different cell types
What are intermediate filaments usually connected to?
Desmosomes
Where else are intermediate filaments found than in the cytoplasm?
Nuclear lamin – on the internal surface of the nuclear envelope – provides support
What are microfilaments made of?
Actin
What do microfilaments associate with?
Adhesion belt
What is the monomer of microfilaments?
G-actin (globular actin)
Define ‘Extracellular Matrix’.
The insoluble material found extracellularly.
What are the four main types of cell-cell junctions (in order of apical to basal)?
Tight – Adhesion belt – Desmosomes/Gap Junctions
What is the role of tight junctions?
Seals off the paracellular pathways. Allows polarity. Stops proteins that diffuse through membranes.
Describe the structure of the adhesion belt.
It consists of a cadherins, which interact with similar molecules on the adjacent cell and clusters to form these junctions. Actin filaments are bound to the adhesion belt.
Describe the structure of desmosomes.
Also involves cadherins interacting to maintain adhesion. Intermediate filaments are associated with desmosomes.
What is the role of Gap junctions?
Allows transport of small molecules between cells.
Describe the differences between squamous, cuboidal and columnar cells.
Squamous are wider than they are tall (plate shaped)
Cuboidal are as wide as they are long
Columnar are taller than they are wide
What are the two types of layering you find in epithelia?
Simple – one layer
Stratified – several layers
What is the difference between keratinising and non-keratinising squamous epithelia?
Keratinising – nuclei are not visible in the surface cells
Non-keratinising – nuclei are visible in the surface cells
Give one example of where you would find: simple squamous, simple cuboidal, simple columnar, stratified squamous (keratinising and non-keratinising) and pseudostratified columnar epithelia.
Simple Squamous – endothelial cells, lung alveolar
Simple cuboidal – kidney collecting duct
Simple columnar – enterocytes
Keratinising Stratified Squamous – skin
Non-Keratinising Stratified Squamous – oesophagus
Pseudostratified columnar – upper airways
What is the key player in establishing epithelial polarity?
Tight Junctions
How do they establish epithelial polarity?
They block the paracellular pathways so molecules that want to pass across the epithelia must pass through the cells.
Why is it necessary for epithelial cells to have polarity?
Many processes (e.g. secretion, absorption) are unidirectional
Describe cell division in the villus
There are intestinal stem cells in the crypt. New cells are shunted up the villus as other new cells form. Cells are lost from the tip.
What type of epithelia usually constitutes protective epithelia?
Keratinising and Non-keratinising stratified squamous
What is Epidermolysis bullosa an example of?
Disorder of cytokeratin and desmosomes
Define extracellular matrix.
Complex network of proteins and carbohydrates which forms the insoluble component of the extracellular environment
What are the three main components of the ECM? Give some examples of each.
Collagen – e.g. collagen type IV
Multi-adhesive glycoproteins – fibronectin
Proteoglycan - aggrecan
Which of these substances are only found in the basement membrane?
Collagen type IV
Laminin
Perlecan
A mutation in the gene encoding which ECM compound causes each of the following disease:
Osteogenesis Imperfecta – Type 1 Collagen
Marfan’s Syndrome – Fibrillin 1
Alport’s Syndrome – Type IV Collagen
Epidermolysis bullosa – Laminin 5 (all three chains)
Congenital Muscular Dystrophy – Laminin 2 (alpha 2 chain)
Give an example of a disease that affects ECM catabolism and the protein affected.
Hurler’s Syndrome – L-alpha-iduronidase
Give an example of a disease caused by excess deposition of ECM.
Lung Fibrosis, Liver fibrosis
Give an example of a disease caused by excessive loss of ECM.
Osteoarthritis
Describe the arrangement of collagen fibres in skin and explain its significance.
Successive layers are at right angles to each other so it can resist tensile force in all directions
What is the structure of a collagen molecule?
It is a stiff triple helix consisting of three alpha chains
Every third amino acid is glycine because only glycine is small enough to fit in the inside of the triple helix. The other two amino acids are commonly proline and hydroxyproline, which form interchain hydrogen bonding that contributes ot the structural integrity of collagen.
Describe the biosynthesis of collagen.
Collagen is synthesised as pro-collagen which has two protruding propeptides, one at each end, which aren’t in triple helical form
Once it leaves the cell, the propeptides are cleaved and the collagen is able to form cross-linkages with other collagen molecules to form collagen fibrils
What is the importance of hydroxylation of proline and lysine in collagen structure?
It allows interchain hydrogen bonding that contributes to the structural integrity and stability of the collagen fibre
Lysine and hydroxylysine is also modified in the formation of covalent cross-linkages after the collagen is secreted – this helps provide tensile strength and stability
What two other substances are needed for hydroxylation of proline and lysine?
Vitamin C and Iron
What are the collagens that don’t form fibrils?
Fibril-associated collagens (e.g. collagen IX) which is involved in the organisation and size of collagen fibrils
Network forming collagens – e.g. collagen IV (basal lamina)
Describe the composition of Elastic fibres.
They consist of an elastin core and microfibrils around the outside that are rich in fibrillin
What causes Marfan’s syndrome and what are some clinical features of Marfan’s Syndrome?
Gene mutation in fibrillin 1
Longer arm span than height – long fingers and toes – predisposed to aortic ruptures
What is the general structure of elastin?
It consists of a hydrophobic region and an alpha-helical region
Give two examples of multi-adhesive glycoproteins.
Fibronectin, Laminin
Where are Laminins found?
Basement Membrane
Describe, in full, the structure of Laminin.
It is a cross shaped molecule consisting of an alpha, beta and gamma chain
It has different parts that have different binding capabilities
The N terminus of all the chains there are globular regions
There is a coiled-coil region, which is the region in which the three chains are wrapped around each other
What causes congenital muscular dystrophy?
Absence of alpha 2 chain in laminin 2
Fibronectin is derived from one gene.
Why is fibronectin considered essential for life?
There are no known mutations of fibronectin in humans
Describe three roles of fibronectin.
Binding to integrin and linking ECM to the actin cytoskeleton – cell binding
Self-association
Binding to other ECM components
What is the general structure of fibronectin?
It is a dimer that is joined by disulphide bonds – it has various domains that can bind to different things
Describe the link between fibronectin and the intracellular compartment.
Fibronectin associated with an integrin which associates with actin – forms a mechanical continuum with the actin cytoskeleton
The fibronectin is also bound to collagen
What part of fibronectin do integrins bind to?
RGD motif
Describe the general structure of proteoglycans.
Consists of a core protein with one or more GAG chains covalently attached
What is the basic structure of GAG chains and what is a characteristic feature of GAG chains?
It is a long, unbranched chain consisting of a repeating disaccharide
It has a large volume
Can form hydrated gels
What are the four families of GAG chains?
Hyaluronan
Heparan Sulfate
Chondroitin Sulfate/Dermatan sulphate
Keratan sulfate
What is unique about hyaluronan?
It doesn’t have a core protein – it is just a massive polysaccharide
It is synthesised on the cell membrane rather than by the ER
How are GAG chains linked to the core protein?
It is connected via a link tetrasaccharide
What does Decorin do?
Regulates collagen fibre size and arrangement
What does hyaline cartilage consist of?
Aggrecan aggregates – consists of aggrecan (GAG chains = keratan sulphate and chondroitin sulphate) associated with hyaluronan and a link protein
Describe how hyaline cartilage resists compressive force.
The GAG chains in aggrecan are heavily sulphated and carboxylated so it is very negatively charged
This means that it can attract osmotically active cations such as Na+ and Ca2+, which attracts water forming a gel like substance
When it experiences a compressive force, the water is squeezed out and the water returns when the compressive force is removed
What causes osteoarthritis?
Loss of extracellular matrix
What happens in fibrotic disorders?
Excess deposition of collagen – normal tissue gets replaced by collagen
What percentage of the fluid in the body is intracellular?
55%
What percentage of the fluid in the body is interstitial?
36%
What are the main cations and anions found inside and outside cells?
Na+, K+, Ca2+
Cl-, Organic Phosphates, Proteins
What is the concentration, in mmol/l, of Na+, K+ and Ca2+ found inside and outside the cells?
Na+ - inside: 10mmol, outside: 140mmol
K+ - inside: 150mmol, outside: 5mmol
Ca2+ - inside: 10^-4mmol, outside: 2mmol
What is the concentration, in mmol/l, of Cl-, Organic Phosphates and proteins found inside and outside the cells?
Protein – outside:1, inside 2
Cl- - outside: 120, inside: 5
Organic Phosphates – outside: 5, inside: 130
What is the pH inside and outside cells?
- 4 outside
7. 1 inside
In which direction does water move due to osmosis?
Membrane permeability to ions
Define tonicity.
The strength of a solution as it affects final cell volume
What do hypertonic, hypotonic and isotonic solutions do?
Hypertonic – make cells shrink
Hypotonic – make cells swell
Isotonic – cells don’t change
What feature do real cells have which prevents them from bursting due to having a higher osmolarity inside the cell than outside?
They have sodium-potassium pumps – maintains a lower concentration of sodium inside than outside
What two forces affect the movement of fluid between the capillary and the interstitial space?
Colloid Osmotic Pressure
Hydrostatic Pressure
What is oedema?
Abnormal collection of fluid in the interstitium due to the leakage of fluid from capillaries (leakage exceeds capacity of the lymphatics to collect and return it to the circulation)
Name the four lobes of the brain.
Frontal
Occipital
Temporal
Parietal
What are the ridges and valleys of the brain called?
Ridges – Gyri, Valleys - Sulci
What are the three parts of the brainstem?
Midbrain – Pons - Medulla
What is the cerebellum responsible for?
Fine tuning motor functions
What are the four broad types of cells in the nervous system? (Named based on their appearance)
Unipolar, Pseudounipolar, Bipolar and Multipolar
What are the three types of multipolar cells?
Pyramidal, Golgi and Purkinje
What are the three main parts of a neurone?
Soma (cell body), axon (only one), dendrites (numerous)
What is the difference between axons and dendrites?
Axons are myelinated and dendrites are not
There is only one axon but there are many dendrites
What are astrocytes and what do they do?
Astrocytes are glial cells that have these functions:
Facultative macrophages (turn into macrophages when they need to)
Repair (provide nutrients for repair of neuronal cells)
Homeostasis (mop up neurotransmitter and other substances released by the CNS)
What do oligodendrocytes do?
They myelinate many axons in the CNS
What are some differences between oligodendrocytes and astrocytes?
Oligodendrocytes are: Smaller Denser cytoplasm and nucleus Absence of intermediate filaments and glycogen in the cytoplasm What do microglial cells do?
What do microglial cells do?
They are the immune cells of the CNS
What do ependymal cells do?
They line the fluid filled ventricles in the CNS
What is the usual resting membrane potential?
Between -40 and -90mV
What are the intracellular and extracellular concentrations of the four main ions involved in action potentials?
Na+ - inside: 10 outside: 140
K+ - inside: 150 outside: 4
Cl- - inside: 5 outside: 120
Ca2+ - inside: 0.1 outside: 2
What is saltatory conduction?
Action potentials jump between adjacent nodes of ranvier (instead of cable conduction) and so it speeds up action potentials
What are the two types of muscle contraction and how do they differ?
Isotonic – tension stays the same and length changes
Isometric – tension changes and length remains the same
What are the two subtypes of isotonic muscle contraction?
Isotonic = Concentric + Eccentric
What is the Z-line made up of?
Alpha-actinin
CapZ
What are the two types of receptors involved in excitation-contraction coupling of skeletal muscle?
Dihydropyridine receptor
Ryanodine receptor
Describe the process of excitation-contraction coupling of skeletal muscle.
An action potential propagates along a T tubule and reaches the Dihydropyridine receptor
Depolarisation causes a conformational change in the DHPR allowing it to make contact with the Ryanodine Receptor on the sarcoplasmic reticulum
RyR opens causing Ca2+ release from the SR
This triggers the muscle contraction
What are the different components of a sarcomere?
Z-line Actin filaments CapZ and Tropomodulin Nebulin Titin Myosin Tropomyosin
What is the structure of actin?
Two twisted alpha helices
What does Titin do?
It holds the myosin in place
It is very large
Where are CapZ and Tropomodulin found?
At the ends of the actin filaments
What is the relationship between tension and load in isotonic and isometric contraction?
Isotonic – Tension > Force
Isometric – Tension = Force
What specialised structure links adjacent cardiomyocytes?
Intercalated Discs
What junctions are present in these structures?
Desmosomes (holds membrane structures together) Gap Junctions (allows electrical communication between cells)
Which receptors are involved in excitation-contraction coupling of cardiac muscle?
Voltage Gated Calcium Channels
Ryanodine Receptors
Describe the process of excitation-contraction coupling of cardiac muscle.
Action Potential propagates down T-tubules and leads to the opening of VGCCs
This leads to influx of Ca2+
Ca2+ then binds to the RyR making them open leading to Ca2+ release from the SR and a further increase in intracellular Ca2+ (Calcium Induced Calcium Release)
Describe the process of excitation-contraction coupling of smooth muscle.
Action potential reaches the VGCC and makes it open leading to Ca2+ influx
Ca2+ binds to Calmodulin forming a Ca2+-CaM complex
This complex activates myosin light chain kinase
MLCK phosphorylates myosin light chains and leads to smooth muscle contraction
What are the three types of signalling?
Autocrine
Paracrine
Endocrine
What type of signalling is glucagon involved in?
Endocrine – it acts on liver cells promoting gluconeogenesis and glycogenolysis
What type of signalling is insulin involved in?
Endocrine – inhibits gluconeogenesis and glycogenolysis in the liver
Paracrine – inhibits glucagon synthesis by nearby alpha cells
Give an example of signalling between membrane attached proteins.
GP120 and CD4 between HIV and T lymphocyte
Give an example of autocrine signalling.
Activated T lymphocytes have IL-2 receptors and secrete IL-2
Describe the signalling that takes place at neuromuscular junctions.
The action potential propagates along the axon and the depolarisation causes the opening of VGCCs
Ca2+ influx
Vesicle exocytosis
Acetylcholine diffuses across the synaptic cleft and binds to sarcolemmal nicotinic receptors that lead to depolarisation of the postsynaptic membrane
Acetylcholine is broken down by cholinesterase and recycled
What are the four types of Signal Receivers?
Ionotropic Receptors
G-protein linked receptors
Enzyme-linked receptors
Intracellular Receptors
Give two examples of ionotropic receptors.
Nicotinic Acetylcholine Receptor
GABAA Receptor
Explain how GABAA receptors work.
Located on many cells in the CNS
Allows transmission of anions
GABA binds to the GABA receptor making it open
Cl- influx
GABA causes a depression of activity
Blocking GABA receptors leads to hyperexcitability of the CNS
Describe the activation process of a G-protein coupled receptor.
The ligand binds and changes conformation of the receptor
The G protein heterotrimer binds to the intracellular compartment (it has a GDP bound to it)
The GDP is exchanged for a GTP
GTP allows the dissociation of the alpha subunit and the beta-gamma subunit
Subunits go and bind to target proteins
Once the alpha subunit has fulfilled its function, the GTP is dephosphorylated (by internal GTPase activity) to GDP allowing the alpha subunit to dissociate from the target protein and reform the heterotrimer with GDP attached
What are two other names for G-protein coupled receptors?
7-TM Receptor
Serpentine Receptor
What are the three types of G-protein linked receptor and how do they differ?
Gs Gi and Gq
They differ in the alpha subunit
Describe the action of Gs-protein linked receptors.
Stimulates adenylate cyclase
Adenylate cyclase converts ATP cAMP
cAMP increases levels of protein kinase A
Give an example of a Gs-protein linked receptor.
Beta-1-adrenergic receptor
Give an example of a Gi-protein linked receptor.
Has the opposite effect to Gs protein linked receptors
Inhibits adenylate cyclase
Describe the action of Gq-protein linked receptors.
Activates Phospholipase C
PLC converts PIP3 to IP3 and DAG
IP3 increases intracellular Ca2+
DAG activates Protein Kinase C
Give an example of a Gq-protein linked receptor.
AT-1 angiotensin receptor
Describe the action of enzyme-linked receptors.
The ligand binds to the receptors leading to receptor clustering
The clustering of receptors leads to activation of intracellular enzymes, which leads to several chemical cascades
The receptors are linked to kinases
What are the three types of enzyme-linked receptor?
Tyrosine Kinase (95%)
Guanylyl-Cyclase
Serine-Threonine Kinase
Give two examples of enzyme-linked receptors.
Insulin Receptor
ErbB Receptor
Describe the action of Type 1 Intracellular Receptors.
Intracellular receptors are bound to heatshock proteins and are found in the cytoplasm
Ligands (usually steroids) pass through the membrane and bind to the receptor
Receptor dissociates from heatshock protein
The receptor and ligand together move into the nucleus and bind to the DNA and causes increased or decreased transcription
These receptors function as homodimers
Describe the action of Type 2 Intracellular Receptors.
These are present in the nucleus and are already bound to the DNA
The ligand passes through the membrane and through the nuclear envelope and binds to the receptor causing changes in transcription
Give an example of a Type 1 Intracellular Receptor. State its ligands, physiological effects and agonists.
Glucocorticoid receptor
Cortisol, Corticosterone
Physiological effect: Downregulate immune response, increase gluconeogenesis
Agonist: Glucocorticoids
Give an example of a Type 2 Intracellular Receptor. State its ligands, physiological effects and agonists.
Thyroid Hormone Receptor
Ligands: Thyroxine, Triiodothyronine
Physiological Effect: Growth and Development
Agonist: Thyroid Hormones
