Tissues

What are neuroglia?

'neuro glue', every other cell type in CNS that aren't neurones

When do you start to grow hair?

- 3rd Trimester in utero (20 weeks lanugo hair and lost before birth)

Types of Galpha subunit in G-protein coupled receptor

- DIFFER IN ALPHA SUBUNIT Gs protein linked receptor o S = stimulatory (sympathetic fight/flight response) o Stimulates adenylate cyclase (target protein) o Adenylate cyclase converts ATP to cAMP o cAMP activates PKA (protein kinase A) o Ligand = adrenaline/noradrenaline o NOTE: beta blockers act on the b1-adrenergic receptor o Effect: increases heart rate and force of contraction o EXAMPLE: b1-adrenergic receptor on heart · Gi protein linked receptor o I = inhibitory (parasympathetic - rest and digest) o Inhibits adenylate cyclase o Ligand = acetylcholine o Opposite effect to the Gs protein - reduces heart rate o Inhibits adenylate cyclase thus reducing levels of cAMP and PKA o EXAMPLE: M2-muscarinic receptor .Gq protein linked receptor o Activates phospholipase C (PLC) o PLC converts PIP2 ----> IP3 + DAG o IP3 ---> increase in intracellular Ca2+ o DAG - activates PKC o Ligand: angiotensin o Effect: smooth muscle contraction and vasoconstriction (leads to high BP) o EXAMPLE: AT-1 angiotensin receptor NOTE: this is just talking about the Ga subunit · PIP2 - Ohosphatidylinositol Bisphosphate · DAG - Diacylglycerol · Angiotensin is a hormone produced in the kidneys which is the most potent vasoconstricter in the body It causes vasoconstriction by acting on the Gq protein linked AT-1 receptor which causes smooth muscle contraction and, subsequently, vasoconstriction.

Name places that don't have hair?

- Everywhere except mucous membranes, palms and soles - 5 million hairs on the body - Only 5% on the scalp

Examples of membrane attached protein signalling

. Circulating T-lymphocyte engages with the MHC molecule on an APC through TCR interaction . HIV GP120 glycoprotein binds to CD4 receptors on T lymphocytes · Bacterial cell wall components bind to toll-like receptors on haematopoietic cells · Platelet aggregation- platelets interact with each other via the glycoprotein tb3a and receptors

Examples of endocrine signalling

. Glucagon secreted by alpha cells in pancreas stimulates gluconeogenesis (only in more extreme hypoglycaemia) and glycogenolysis in the liver --> increasing blood glucose levels · Insulin (produced in pancreas acts on liver, muscle cells and adipose tissue) · Adrenaline produced in adrenal glands acting on the trachea and bronchi (dilates airways so more air comes in), also acts on other organs like heart · Prolactin produced by pituitary gland and acting on mammary glands

Systemic nail diseases

. clubbing . Beau's lines - ridge In nail . Koilonychia - curving upward spoon shape, can indicate iron deficiency anameia . Psoriasis also affects nails as well as skin - pitting , salmon spots (plaques underneath nail), onycholysis (splitting of nail plate from bed)

What temp is organ cooled to transplantation

0 to +4°C. Tissues are perfused with cold solutions via the arterial supply.

How many keratinocytes per melanocyte?

1 melanocyte every 5th keratinocytes. Brown pigmentation in pic below - melanocytes. Can also see the melanin in darker purple colour

Synaptic transmission

1) AP is propagates by VGSCs opening, when action potential arrives at the presynaptic membrane due to Na+ influx, the depolarisation causes the opening of VGKC (dense at end of presynaptic terminal), leading to K+ efflux causing repolarisation. 2) AP causes voltage-gated Ca2+ to open and influx of Ca2+ 3) Ca2+ causes vesicular exocytosis 4) Ca2+ fuses with the vesicles containing neurotransmitter and causes exocytosis. 5) Neurotransmitter binds to receptors on the post-synaptic membrane and converts the chemical signal to an electrical signal. 6) Neurotransmitter reuptake - after neurotransmitter released from receptors, either metabolised by enzymes in the synaptic cleft and taken back up by the axon terminal or it's recycled by transporter proteins.

Examples of epithelial proliferation

1) Cells of the basal layer of stratified squamous epithelia divide to replace cells lost from the surface. 2) Cells in intestinal crypts replace cells lost from the tips of intestinal villi.

List the major components of the ECM

1) Collagen Major fibrillar proteins providing tensile strength 2) Multi-adhesive glycoproteins 3) Proteoglycans 4) Basement membrane: Collagen IV and laminins

Dermatan sulfate vs chondrotin sulfate (types of GAGs)

1) Dermatan Sulfate NOTE: Carboxylate and sulfate group make it negatively charged 2) Chondroitin Sulfate NOTE: Chondroitin Sulfate has glucuronic acid instead of iduronic acid

What are the main fluid compartments and sizes in a lean 70kg man?

1) Extracellular (EC) = (19L) 45% of body water made of: o interstitial fluid between cells (15L/36% of body water) o blood plasma (3L/7%) o transcellular fluid e.g. CSF, ocular, synovial fluid (1L=2%) 2) Intracellular (IC)= (23L) 55% of body water · The majority of the fluid is intracellular · Out of the extracellular fluid in a person, the majority of it is interstitial fluid. · A small proportion (7%) is blood plasma An even smaller proportion (2%) is transcellular fluid e.g. cerebrospinal, ocular, synovial fluid

Examples of collagens that don't form fibrils

1) Fibril-Associated Collagens - e.g. Type IX + Type XII - associate with fibrillar collagens and regulate the organisation and size of collagen fibrils. 2) Network-Forming Collagen - . Type IV - is a sheet network-forming collagen. present in all basement membranes - molecular constitution varies from tissue to tissue.

Saltatory conduction

1) If there was no myelination - you get slow movement of action potentials along the axon via cable transmission 2) Myelin prevents the action potential from spreading because it has high resistance and low capacitance 3) Nodes of Ranvier (small gaps of myelin intermittently along axon) have a dense concentration of VGSCs and VGKCs 4) Action Potentials jump between Nodes of Ranvier (saltatory conduction) allowing faster conduction. Although can jump between nodes, AP is unable to 'jump' across the gap at the axon terminal (presynaptic axon terminal), hence need synapse. Disorders of myelin - e.g. multiple sclerosis - diff to move + transmit signals

List examples of intracellular signalling

1) Ionotropic receptors 2) G-protein coupled receptors 3) Enzyme-linked receptors 4) Intracellular receptors

What are the two main communication systems in the body?

1) Nerve fibres of the central and peripheral nervous system 2) The blood vessels of the cardiovascular system

Why do cells need to communicate?

1) Process Information o Sensory stimuli - e.g. sight, sound 2) Self Preservation o Identify danger and take appropriate actions ○ Spinal reflexes ○ Sympathetic nervous system (fight or flight response - increase heart rate, blood flow through skeletal muscle, pupils dilate) 3) Voluntary Movement o Getting from A to B o Completing daily tasks 4) Homeostasis o Thermoregulation and Glucose homeostasis

Function of hair

1) Protection (minor trauma and UV light (cancer) 2) foreign bodies and water prevented by eyelashes) 3) sensation (sensory supply around hair shaft) 4) thermoregulation (more for animals) (these 3 are all physiological) 5) communication (attractive ;))

Function of nails

1) Protection (weapon) • Chemical, physical 2) Touch • Manual dexterity 3) Communication - socially 4) Cosmetic purpose

How are epithelium classified?

1) SHAPE - e.g. cuboidal, squamous (flattened plate-shape), columnar 2) LAYERING - e.g. single layer = simple; multi-layered = stratified

What two structures do myofibres have?

1) T-tubules - membrane invaginations that contact the extracellular fluid 2) Sarcoplasmic reticulum (SR): extensive network of Ca2+ stores surrounding each myofibril

Neurone morphology

1) Unipolar o Has a cell body and one axon in one direction. o Rarely found in the CNS (1% of total neurones) o Mainly found around the retina (visual cortex). 2) Pseudo-unipolar o Single axonal projection from cell body, which splits into two o Rarely found in the CNS o More present than unipolar, found in ganglions (cluster of neural bodies outside CNS) o Mainly found in the pain pathway in the PNS 3) Bipolar o Two projections from the cell body (1 axon, 1 dendrite). o Rarely found in the CNS 4) Multipolar - COMMON o Numerous projections coming from the cell body o ONLY ONE AXON - the rest are dendrites o Multipolar neuronal cells can have many morphologies: a) Pyramidal Cells - pyramid shaped cell body b) Purkinje Cells - GABA neurones found in the cerebellum c) Golgi Cells - GABA neurones found in the cerebellum NOTE: the cell body of neuronal cells is really small and the rest of the cell is just projections - so the cell body needs support from other parts of the nervous system. ALWAYS HAVE ONLY ONE AXON regardless of neurone morphology

what are the three main components of ECM?

1) collagen e.g. type IV collagen 2) proteoglycans e.g. aggrecan 3) multi-adhesive glycoproteins e.g. fibronectin

2 types of sweat glands

1) eccrine - all over body, salty sweat 2) apocrine - under hair follicle, viscous sweat can be metabolised by bacteria

What are the 4 main cell types?

1) epithelial cells: cells forming continuous layers, these layers line surfaces and separate tissue compartments. form carcinomas 2) mesenchymal cells: cells of the connective tissues, e.g. fibroblasts (many tissues), chondrocytes (cartilage), osteocytes (bone), muscle cells (skeletal, cardiac, smooth), the endothelial cells lining blood vessels. form sarcomas 3) haematopoietic cells: blood cells and the cells of the bone marrow from which they are derived. form leukemias (bone marrow cells) or lymphomas (lymphocytes) 4) neural cells: cells of the nervous system having two main types; neurones (carry electrical signals) and glial cells (support cells). form neuroblastomas (from neurone precursors) or gliomas (from glial cells)

Varied properties of connective tissues

1) tendons and skin - tough and flexible 2) vitreous humour - soft and transparent 3) bone - hard and dense 4) cartilage at ends of bones - resilient and shock-absorbing Different connective tissues have different properties - dependent on the composition of the extracellular matrix. How collagens assemble and what they interact with dictates the properties of the tissue.

Experiment showing how tight junction seals the paracellular pathway

1. A tracer substance added to the apical face of the epithelium cannot penetrate between the cells; it is restricted by the apical tight junction. 2. TEM shows the restriction of passage of the tracer (black) when added apically. When added to the basal aspect of the epithelium, the tracer is able to pass into the narrow intercellular space until it reaches the apical TJ, when it is prevented from passing to the apical region

What are the outcomes of sealing the paracellular pathway by tight junctions?

1. Concentration differences across cell layers can be maintained i.e. Solutes like glucose, are often pumped across call layers against a concentration gradient. if not for sealed paracellular pathways gradient would be lost by back diffusion between cells 2. Any solutes crossing the cell layer need to pass through the cells, meaning that the cells control the passage. Strong barriers are particularly required when tissues need to transport against a large concentration gradient.

Human disorders resulting from ECM abnormalities

1. Gene mutations affecting matrix proteins o Osteogenesis Imperfecta - Type I Collagen o Marfan's Syndrome - Fibrillin 1 o Alport's Syndrome - Type IV Collagen (a5) o Epidermolysis Bullosa - Laminin 5 (in all 3 chains) o Congenital Muscular Dystrophy - Laminin 2 (a2 chain) 2. Gene mutations affecting ECM catabolism o Hurler's Syndrome - L-a-iduronidase o Other mucopolysaccharidoses - inability to degrade GAGs (glycosaminoglycans) Mutations in different types of collagens, multi-adhesive glycoproteins and proteoglycans can cause disease. There can be mutations where matrix molecules aren't affected but enzymes that are involved in MATRIX CATABOLISM are affected. 3. Fibrotic disorders due to excessive ECM deposition o Liver fibrosis - Cirrhosis o Kidney Fibrosis - diabetic nephropathy o Lung Fibrosis - silicosis 4. Disorders due to excessive LOSS of ECM o Osteoarthritis FIBROSIS IS CHARACTERISED BY HAVING TOO MUCH MATRIX. SOME DISEASES ARE CAUSED BY TOO MUCH LOSS OF MATRIX e.g. osteoarthiritis.

Overall functions of skin

1. Protection against injury 2. Protection against pathogenic organisms 3. Waterproofing and fluid conservation 4. Thermoregulation 5. Absorption of ultra violet radiation and vitamin D production 6. Sensory organ 7. Cosmetic

Hair growth: the hair cycle

3 phases: Anagen, catagen, telogen Anagen: growth - done in bulb area --> grow for months of years. highly vascularised. energy intensive. Catagen - resting phase - end of shaft keratinised, forms club shape. dermal papilla moves towards base of muscle insertion Telogen - shedding phase, then anagen starts again. club hair can take 4-6 weeks to be released

What are the typical water concentrations in women and men?

55% in women. 60% in men

Microtubule arrangment

9 microtubule doublets and 2 central microtubules make up the core of cilia and flagellae: the 9+2 arrangement. ATP-dependent motor proteins (blue in pic below) distort the cilium or flagellum to produce movement. Longitudinally you can see the microtubules running along the cilium.

Signalling between membrane attached proteins

= plasma membrane proteins on adjacent cells interacting · Blood borne virus (e.g. Hep C) is detected in the blood stream by an APC · APC digests the pathogen an expressed MHC class II on the surface · Circulating T-lymphocyte engages with the MHC molecule through TCR interaction Other examples of membrane attached protein signalling: · HIV GP120 glycoprotein binds to CD4 receptors on T lymphocytes · Bacterial cell wall components bind to toll-like receptors on haematopoietic cells · Platelet aggregation- platelets interact with each other via the glycoprotein tb3a and receptors

Cell turnover in tissues

A balance between cell proliferation and cell death is key to maintaining the architecture of tissues In most tissues, cells die and are replaced. The rate at which this happens varies considerably. The lining of the gut is replaced every 3-10 days (depending on region). Fat tissue, heart muscle and bone are replaced every 8-10 years. Most neuronal cells of the central nervous system are not replaced. If they die, they are lost.

What is collagen?

A family of fibrous proteins found in all multicellular organisms. · 28 different collagens · The most abundant protein in mammals - 25% of total protein mass · Major proteins in bone, tendon and skin · 'a protein that is the principal constituent of white fibrous connective tissue (as occurs in tendons). Collagen is also found in skin, bone, cartilage and ligaments. It is relatively inelastic but has a high tensile strength.' NOTE: Fibroblasts make the extracellular matrix components.

Intermediate filaments

A group of polymers of filamentous proteins which form rope-like filaments - give mechanical strength and stabilise nuclear envelope · Diameter - 10-15nm (Intermediate because their diameter is in between microtubules and microfilaments) · Different cell types have different intermediate filaments (e.g. epithelial cells - cytokeratin; mesenchymal cells - vimentin; neurons - neurofilament protein; muscle cells -desmin) · IFs give mechanical strength to the cells and stabilise nuclear envelope · Desmosomes are connected by intermediate filaments (epithelial cells - cytokeratin. muscle cells -desmin) Nuclear Lamins - intermediate filaments which form a network on the internal surface of the nuclear envelope - they are involved in stabilising the envelope.

What is a motor unit?

A motor neurone and all its muscle fibres

Under normal, healthy conditions for a 70kg man, how much fluid leaks from blood vessels into interstitial spaces?

A significant amount (8L/day)

Each skeletal muscle fibre is a single cell bounded by the sarcolemma. True or false?

A skeletal muscle fibre is a single cell (long and thin) surrounded by a surface membrane, which is named the 'sarcolemma'. The prefix 'sarco-' refers to skeletal muscle. Fibre vs filament: A filament is an assembly of proteins with a long rod-like shape.

What is hyperkalemia?

A sreum potassium level that exceeds 5.1 mEq/L. High potassium outside cell. Treat this with calcium as it stabilises the membrane Treat with insulin as it shifts potassium into cells

Cytoskeleton components

A system of 3 types of filaments formed by the polymerisation of protein monomers: microtubules, intermediate filaments, microfilaments

Which of the following types of neurones has only one axonal projection from the cell body?

ALL OF THEM Bipolar, multipolar, pseudo-unipolar, unipolar

Which protein component of a sarcomere does the crossbridge repeatedly attach to and detach from during contraction?

Actin. During contraction, the crossbridge (part of the myosin molecule) goes through repeated cycles of attachment to and detachment from the actin filament.

What is responsible for resisting compressive forces in cartilage?

Aggrecan. Proteoglycan. Highly sulphated and negatively charged. It can retain large quantities of water. Under compressive load, water is given up, but regained upon reduction of the pressure.

Which substance is a major cartilage matrix component, it is a supramolecular complex comprising a core protein, link proteins, chondroitin sulfate, keratan sulfate, and hyaluronan?

Aggrecans. Aggrecans are mainly negatively charged due to the GAGs and carboxyl groups. The negative charges attract Na+, which is osmotically active. Hence, large quantities of water associate with the aggrecan molecules and under compressive load, water is lost but regained under reduced loads.

What two amino acids are rich in the alpha helical regions in elastin?

Alanine and lysine

Components of connective tissue

All connective tissues contain a distinct spectrum of collagens, multi-adhesive glycoproteins and proteoglycans (extracellular matrix) together with a cellular component · Collagens o Type I, II and III (fibrillar) o Type IV (basement membrane) NOTE: ALL ECM HAVE SOME FORM OF COLLAGEN · Multi-Adhesive Glycoproteins: o Fibronectin, Fibrinogen o Laminins (basement membrane) · Proteoglycans: o Aggrecan, Versican, Decorin o Perlecan (basement membrane) NOTE: MATRIX can influence cellular behaviour as matrix COMPONENTS INTERACT WITH SPECIFIC CELL SURFACE RECEPTORS FOUND ONLY IN THE BASEMENT MEMBRANE o Collagen - Type IV o Multi-adhesive glycoproteins - Laminins o Proteoglycans - Perlecan

How does action potential propagate along muscle?

Along muscle membrane (sarcolemma) through T-tubule system of myofibres

Intestinal villi and glands

Already looked at small intestinal villi (tongue-like shape). However, numerous tubular epithelial glands extend into the wall of the gut, in both the small intestine, which has villi and glands, and in the colon, which lacks villi but has numerous glands. These glands have important roles in epithelial-turnover.

What are the main subunits making up the nuclear pore?

Annular, luminal, ring and column

Apart from barrier and protective function of skin, what else does it do?

Another function of skin is production of vitamin D upon UV exposure: get rickets if not enough vit D (bones don't develop properly) and other signs. Also weaker immune system and predisposed to certain cancer. For adults insufficient vit D --> get osteomalacia (soft bones more likely to fracture)

Juxtacrine signalling

Another type of signalling where instead of acting on a cell that is two cells down, the secreted product acts on the immediately adjacent cell

What's the most abundant cell type in CNS?

Astrocyte

Where is hyaluronic acid synthesised?

At the cell surface

What are the consequences of defects in cytokeratins or cell-cell junctions?

BLISTERING DISEASES as a result of EPIDERMAL DAMAGE e.g. Epidermolysis Bullosa

What does epithelium lie on?

Basal lamina

Why is creatine kinase being found in serum not diagnostic of MI?

Because have isoenzymes of creatine kinase - need particular isoenzyme - BM

Example of intracellular signalling in glucose homeostasis

Between alpha and beta cells within the islets of langerhans

Bone connective tissue

Bone is a specialised connective tissue where the ECM (termed osteoid) has become mineralised with calcium phosphate crystals to provide great compressive strength. The relatively solid region around the edge of the bone shaft is known as compact bone or dense bone. Within it there are the support cells of bone, called osteocytes, within lacunae. There are also other cavities containing blood vessels. The mineral prevents free diffusion, and small channels called CANALICULI provide a pathway for diffusion of O2 and nutrients from the blood vessels to the osteocytes. In transverse section on that slide it can be seen that bone is arranged in structural units called osteons or Haversian systems which have a central canal containing blood vessels, with the ECM of the bone arranged in concentric layers around this central canal. The collagen fibres are oriented differently in each layer to provide additional strength. The central part of a bone has spaces between the bone tissue, and is known as spongy bone or cancellous bone. The bony structures here are called trabeculae, and they are usually arranged in the way that best resists the mechanical stresses on the bone. Most of the space between the trabeculae is filled with bone marrow, the site of developing blood cells. There may also be fat cells. Because the mineral component of bone can act as a store for Ca2+ and phosphate, bone resorption and formation are under hormonal control from calcitonin and parathyroid hormone to maintain the normal blood concentrations of these ions. Most bones start as cartilage precursors in the foetus, which then get converted to bone - a process known as endochondrial ossification. In long bones, a cartilaginous region persists at the growth plates between the shaft and heads until the bone has reached its adult length. Cartilage also lines the bone surface where it forms part of a joint. Elsewhere the bone is lined with a layer of dense connective tissue - the periosteum.

By convention how is gene shown?

By convention the gene is shown as the coding (or sense) strand, i.e. the one equivalent to the mRNA except that it contains thymine (T) instead of uracil (U). During transcription it is in fact the other strand of the DNA which gives rise to the precursor mRNA by complementary base pairing.

What is osmolarity?

CONCENTRATION OF ALL SOLUTE PARTICLES in a solution

In smooth muscle which protein binds to calcium ions to initiate the process of contraction?

Calmodulin

Compare size of cardiac cells and smooth muscle cells

Cardiac cells are larger than smooth muscle cells

Epithelial-turnover in the small intestine

Cell Division in the Villus • ISC - Intestinal Stem Cells • ISCs are present in the crypt • There is a constant turnover of cells. • Cells are lost at the tip and are produced in the crypt. It acts like an escalator - as the cells mature they move up towards the tip of the villus.

Where does cell division for the renewal of surface epithelial cells occur?

Cell division, for the renewal of the surface epithelial cells, is by stem cells in mid-region of the intestinal crypts

Summary of cell turnover and epithelia

Cell turnover: summary of the basic principles In tissue cell turnover, cells lost from the tissue are replaced by new cells. • cell loss = cell production; steady state • cell loss > cell production; reduction in tissue mass cell loss < cell production; increased tissue mass Changes to the steady state can be normal physiological responses, or pathological. Striking examples of normal physiological responses are found in female reproductive biology. the cyclic production and loss of the endometrial epithelial lining of the uterus in the menstrual cycle. the large increase, during pregnancy, in the number and size of the epithelial glands of the breast, and their loss after weaning (stopping breast feeding). Summary Epithelial tissues are widely distributed in our bodies, forming major tissues in a number of organs and organ systems. The range of their functions reflects this wide distribution. We have emphasised the importance of cell-cell adhesion, and the cell-junctions involved, in the formation, maintenance and function of epithelial layers. Cell-turnover in tissues is clearly an important process that impacts on tissue organisation and maintenance. We have seen that any imbalance in cell-turnover can have profound effects on tissues.

What is the epithelium?

Cells forming continuous layers, these layers line surfaces and separate tissue compartments and have a variety of other functions.

How can changes in Ca2+ conc be detected?

Changes in Ca2+ concentration can be detected by proteins e.g. calmodulin

Name three structures that microtubules are part of

Cilia, flagella, mitotic spindle

Arrangement of collagen fibrils

Collagen Fibrils have a Staggered Arrangement · Skin - fibres run parallel but they cross in all directions - can resist tensile force in all directions. · Parallel Bundles - resist tensile force in one direction. · Tendon - you only get tensile strength in one plane (all parallel). N.B. more stain in gap regions Ehler's Danlos syndrome - stretchy skin, where collagen fibrils are weaker - low tensile strength.

What is the diameter of collagen?

Collagen fibres have a diameter of about 3 µm

Collagen biosynthesis

Collagen is made as procollagen in the endoplasmic reticulum. · Procollagen (newly synthesised collagen) has (non-collagenous domains) N and C regions which are NOT in triple helices. · Once OUTSIDE the cell - the N and C propeptides are removed by extracellular proteases in case of FIBRILLAR collagens, but REMAIN part of collagen in MOST other types. Hydroxylation of lysine and proline - for H bonds. Lysine and hydroxylysine are modified --> covalent cross-linkages The collagen is then released and forms fibrils with cross-linkages between different collagen molecules.

How does conduction velocity change with diameter and myelination?

Conduction velocity is greater along axons of larger diameter. Myelinated axons have greater conduction velocity than non-myelinated axons of the same diameter.

What does the subcutaneous layer of skin consist of?

Connective tissue and fat

Connective tissue general features

Connective tissue is the general name given to a family of tissues including cartilage, bone, tendons and ligaments as well as those commonly referred to as loose or dense connective tissue. They have a number of features in common: • The support cells which maintain the tissue are not necessarily attached to one another (i.e. unlike epithelial cells). • The majority of the volume in most (though not all) connective tissues is taken up by extracellular matrix. • Other cells may be present, for example those with immunological functions. • The tissues are derived from mesenchyme, an embryonic tissue principally associated with the mesoderm layer of the early three layer embryo. However, the support cells are specialised to the particular tissue, and in particular to producing extracellular matrix (ECM) with the necessary properties. In all cases the ECM components can be reduced to three types: • Fibrillar structures which provide strength against tensile forces applied to the tissue. Their main protein components are collagen, elastin and fibrillin. • A viscous liquid component which provides resistance to compressive forces applied to the tissue. The main molecular components are complex negatively charged polysaccharides which bind water and Na+ ions and are mainly glycosaminoglycans or proteoglycans. The liquid component also provides a solvent in which oxygen, nutrients, waste products and small signalling molecules can diffuse. • Other molecules whose main function is in binding to cells via specific cell surface receptors and mediating their attachment to the ECM. The best known example is fibronectin.

What kind of cross-links are found between elastin molecules?

Covalent cross-links

Which intermediate filament connects desmosomes?

Cytokeratins (polymers of filamentous rope-like proteins) are associated with epithelia. Different intermediate filament types are expressed by different cell types

Why is osmolarity too simple to use for biological systems?

DOES NOT DEPEND ON CELL PERMEABILITY

Melanonychia

Darkening of the fingernails or toenails

What is the hypodermis?

Deep, subcutaneous adipose layer and acts as both a fat and heat store.

What do the different properties of different connective tissue depend on?

Depends on the composition of the ECM

What are the components of the dermis?

Dermis- supportive connective tissue matrix o Collagen (70%), elastin, glycosaminoglycans (GAGs) o Fibroblasts o Immune cells o Blood vessels, lymphatics

What happens when cell turnover becomes unbalanced?

Disturbing the balance of cell proliferation/loss affects tissue dynamics: REDUCING cell proliferation. Treating mice with the antimetabolite chemotherapy drug, 5-FU, has a profound effect on the architecture of the small intestinal villi. The drug slows down or stops cell division in the crypts. Cell loss from the villus tips continues as normal, but the failure to produce new cells to replace the cells results in a loss of tissue: the villi shorten. This is the reason why chemotherapy can have strong gut side-effects. Disturbing the balance of cell proliferation/loss affects tissue dynamics: INCREASING cell proliferation. When there is too much cell proliferation, the rate of cell loss is not sufficient to maintain the normal tissue volume. In the colon, if a cell mutates such that its proliferation is dysregulated, too much tissue is formed. This is a benign tumour called an adenoma (polyp). Although not malignant, these adenomas have a high risk of acquiring more mutations that switch it to cancer (adenocarcinoma)

What is a dominant negative condition?

Dominant negative- small thing there is not good and dominates effects. A mutation whose gene product adversely affects the normal, wild-type gene product within the same cell

Why are skeletal muscle fibres multinucleated?

During development, muscle fibres form by fusion a many cells, each containing a single nucleus.

What type of proteins are in ECM?

ECM molecules are large, modular proteins (50-200AAs). Most major proteins are glycosylated (proteoglycans or glycoproteins) · Most ECM proteins are very LARGE · They have MODULAR architecture - they are composed of protein domains of 50-200 amino acid residues (each of the units in the diagram is a protein molecule) · Multifunctionality of ECM proteins due to modular structure · Many large modular proteins are multi-adhesive, binding various matrix components and cell-surface receptors Example: perlecan. Each shape in perlecan shows domain of same type

Pubic louse

Ectoparasites: Adapted to grip thick terminal hair (pubic hair and beard hair, axillary, eyebrows, eyelashes or in hairy man can occur all over) - Not scalp hair though. related to gorilla louse. Use eye ointment to treat lice on eyelashes and pick up, on other hair used specialised shampoo Pubic lice = short and fat.

Elastin

Elastin has two types of segments that alternate along the polypeptide chain. · Two types of segment: Hydrophobic regions and a-helical regions (rich in alanine and lysine) · Many lysine side chains are covalently cross-linked Elastin is like a rubber band - it changes its configuration when stretched, when the stress is removed, it will return to its original configuration.

Mitochondria info

Energy metabolism - production of ATP - the number of mitochondria you see in a cell is indicative of the cell's metabolic activity. Double membrane. Don't akways have the simple, small, sauasage-like shape, can have elaborate, branched morphologies

How are dermis and epidermis connected?

Epidermis from ectoderm, dermis from mesoderm and stuck together by various proteins. Numerous protein that sticks epidermis to basement membrane, proteins within basement membrane and also proteins that basement membrane onto dermis (e.g. hemidesmosome, tonofilaments, anchoring fibrils and filaments etc.). If defective proteins in basement membrane : weakness in basement membrane, epidermis splits from dermis, and blister formation. Also if immune reaction where immune cells/ antibodies attack protein causes splitting. Clinical conditions associated: Epidermolysis bullosa and bullous pemphigoid

What is the correct order from top to bottom? hypodermis, epidermis, dermis

Epidermis is external to dermis which is external to hypodermis

Consequences of defective basement membrane

Epidermolysis bullosa = if one of proteins is detective --> shearing of epidermis off the dermis in minor trauma and causes blistering in severe form. Often try to repair itself, but leaves scars and ulcers. Dies in 20s due to skin cancer from inflammation. Rare condition: genetic disorder that affect proteins. Only 60-70 in UK. Bullous pemphigoid - auto antibody formation (antibody is made against one of the proteins in the basement membrane) --> blister formation. Acquired not genetic, in older people. Quite common. Do biopsy to see. Treat with steroids (topical and systemic) to suppress immune system

Epithelial cells basic info

Epithelial cells form stabilised, stable cell-cell junctions to form continuous, cohesive layers. · Line body surfaces externally and internally · Involved in variety of functions: transport, absorption, secretion and protection · cell-cell junctions key to the formation and maintenance of epithelial layers

Tissue diversity

Estimated that there are 37 trillion cells in the average, human body. There are approximately 200 cell types in the human body, which arise from division and cell differentiation during development.

Why does osteogenesis imperfecta have dominant pattern of inheritance

Even if patient is heterozygous, so only some of alpha1 (1) chains are abnormal while the others is making a normal version, because collagen triple helix contains 2 alpha1 (1) chains, it will be disrupted if only one is mutant form and majority of collagen fibres will be affected leading to dominant phenotype. N.B. in principle if heterozygous, there should be 50% normal and mutant, but this may differ based on rate of transcription, translation, stability of mRNA and stability of protein

clubbing of nails

Excessive curvature of nail and proximal nail fold area is swollen. Need to think of number of causes- CV disorders and respiratory

What are the hallmarks of osteoarthritis?

Excessive extracellular matrix degradation and loss of aggrecan to synovial fluid

Neurones

Excitable cells of CNS- ability to change their membrane potential and send action potentials along their axon. · Heterogenous Morphology - lots of different types of cells · Non-dividing cells (possibly can now within certain regions of brain e.g. hippocampus) · Common Features: 1) Soma (cell body, perikaryon) · Nucleus and Ribosomes · Protein production · Neurofilaments - type of intermediate filament provides structural support and transport 2) Axon · It's a multipolar cell but only have ONE AXON · Long process (aka nerve fibre) which originates from soma at axon hillock · Can branch off into collaterals · Myelinated and responsible for conduction action potential 3) Dendrites · Highly branched cell body from soma · NOT MYELINATED · Receive signals from other neurons

What type of secretion is the pancreas most associated with? Endocrine or exocrine?

Exocrine. Only certain cell types secrete hormonal products e.g. α-cells producing glucagon.

What is the relationship in osmolarity between extracellular and intracellular fluid

Extracellular and Intracellular have the SAME OSMOLARITY (except in some parts of kidney)

Cytoskeleton is NOT

FIXED. IS DYNAMIC. The various elements of the cytoskeleton are subject to rapid remodelling by a variety of biochemical and bio-mechanical signals.

What are basement membranes and what are the two main components?

FLEXIBLE thin mats of ECM underlying epithelial sheets and tubules. Two main components are collagen type IV and laminins. Also contains perlecan

ASSERTION: Osteogenesis imperfecta is much more common in males than females REASON: The gene defective in osteogensis imperfecta is on the X chromosome.

False, false. The assertion is false because the incidence is the same in males and females. The reason is false because OI is most commonly due to a defective gene for collagen 1 on chromosome 17, not on the x chromosome.

ASSERTION: Tendon resists tensile force in all directions REASON: Collagen fibrils in tendon are arranged in parallel bundles

False, true. Assertion is false because tendons only resists tensile force in one direction

ASSERTION: Microvilli at the apical surface of epithelial cells can actively move material over the cell layer REASON: Microvilli have an actin bundle at their core

False, true. Microvilli are too small to actively move substances across the surface, but villi are able to.

A sarcomere can elongate by using the energy from ATP hydrolysis. True or false?

False. A sarcomere cannot actively elongate because the crossbridges can only produce a force directed toward the centre of the sarcomere. Consequently antagonistic pairs of muscles are needed for joint flexion and extension.

The thin actin filaments are highly extensible. True or false?

False. The thin filaments are highly INEXTENSIBLE.

A neurone contains both sensory and motor axons. True or false?

False. A NERVE contains both sensory and motor axons, not a neurone.

Myosin, actin, troponin and tropomyosin are the only structural proteins in skeletal muscle. True or false?

False. These are only some of the proteins present.

the sole fate of modified products from the GA is extracellular secretion. True or false?

False. Vesicles originating from the GA carry material to for extracellular secretion and also towards other organelles.

A tall male athlete with long legs and arms dies of a ruptured aorta. Similar deaths have occurred in extended family. Gene for which protein is likely mutated in this patient?

Fibrillin

Summary of specific ECM molecules mentioned

Fibronectin - glycoprotein. V-shaped molecule. Interact w/ actin via integrin (RGD between integrin and fibronectin) Decorin - proteoglycan. small GAG chain attached. binds to collagen- for regulation fibrillogenesis Aggrecan - proteoglycan for resisting compressive pressure in cartilage. highly sulphated and negative, gives up water. consists of aggrecan, GAG (hyaluron) and link protein. Laminin - glycoprotein. cross-shaped molecule. forms sheet-like network in basement membrane

What is university of wisconsin solution?

Formulated to reduce hypothermic cell swelling and enhance tissue preservation in organ transplantation. · Meant to mimic interstitial fluid but slight differences · Provides: o no Na+ or Cl- (no influx possible) o extracellular impermeant solutes (lactobionate ions, raffinose (a sugar)) o macromolecular colloid (starch) Together, these factors reduce cell swelling in cooled tissues.

When the voltage across a cell membrane is measured, the 0 V reference is from where?

From outside the cell. By convention the outside is taken as the 0 V reference. Measurements are always of the inside relative to the 0 V outside.

What is the monomer of microfilaments?

G-actin (globular actin)

How are GAG chains attached to core proteins in proteoglycans?

GAG chains and the core protein of a proteoglycan are linked via a LINK TETRASACCHARIDE

Basement membrane in the glomerulus

GLOMERULUS - basic filtration unit in kidney. Basement membrane prevents macromolecules going from the blood into the nephron.

Three types of tonicity

HYPERTONIC · Osmolarity of impermeant solutes: out > in · Cell shrinks in solution · Solution is hypertonic HYPOTONIC · Osmolarity of impermeant solutes: out < in · Cell swells in solution · Solution is hypotonic ISOTONIC · Osmolarity of impermeant solutes: out = in · Cell volume is unchanged · The solution is isotonic Differences in the concs of permeant solutes can result in transient changes to cell volume. If the difference is very large, it can result in damage.

pilosebaceous unit

Hair is made up of pilosebaceous units: The hair unit that contains: o hair follicle (invagination of epidermis - so lining of follicle is epidermis) o appendages: - hair root - hair shaft - outer cuticle that encloses a cortex of packed keratinocytes and an inner medulla (in terminal hairs) - hair bulb - fed blood by dermal papilla; germinative cells (in pigmented hair there are melanocytes) - dermal papilla - vasculature, sensitive to androgens - sebaceous gland (makes sebum oil that lubricates oil and contains chemicals to prevent infection (fungal and bacteria), is also what causes greasy hair/skin) - arrector pili muscle (smooth muscle under sympathetic control - in cold will contract to form goosebumps).

What is the function of hemidesmosomes?

Hemidesmosomes are found on the basal surface of epithelial cells and are present in the dermo-epidermal junctions of the skin. Desmosomes attach 2 cells together

Why do sebaceous glands look white in histology?

High lipid content Hairy skin histology: includes adnexal structures like hair follicles. Sebaceous gland has high lipid content --> so looks white

What is permeability?

How easily a solute crosses a membrane

Which substance is a single unsulfated GAG chain and does not associate with a protein core?

Hyaluronan or hyaluronic acid is just a carbohydrate chain, synthesised at the cell surface.

Which part of the myofibril is the light band that is intersected by a dark line?

I-band

Eccrine vs apocrine sweat glands

Image of sweat gland: eccrine gland opens directly onto surface of skin. Apocrine gland open into infundibulum (funnel) of hair follicle Eccrine gland: Tubular structure and coil down in dermis

Explain the structural and functional significance of hydroxyproline and hydroxyleucine found in ECM? (3)

Important in structure and function of collagen. They contribute to inter chain hydrogen bond formation. Hydroxylysine is also modified (glycosylated) in the formation of covalent bond cross links after collagen has been secreted that help to provide tensile strength and stability

In which organisms is ECM found ?

In ALL metazoans. i.e. even in organisms with 2 cell layers such as Hydra vulgaris

What is shown in this diagram?

In State 1 the tropomyosin (labeled B) blocks the myosin-binding site (labeled C) on actin so the crossbridge cannot attach and the muscle is in its resting, non-contracting state. In state 2, which corresponds to contraction, the tropomyosin has moved so that the myosin-binding site is exposed and available to crossbridge attachment. B= tropomyosin C= myosin binding site

In cardiac cells, what is the relationship between the shape of the action potential and the heart rate?

In cardiac cells, the shape of the action potential is almost independent of heart rate

Ca2+ is actively transported into the sarcoplasmic reticulum (SR) during muscle contraction. True or false?

In fact both release and uptake are happening during contraction. The Ca2+ concentration around the filaments is high during contraction because the amount released from the SR is greater than the amount actively transported back into the SR. Ca-ATPase pumps Ca2+ back into the SR continuously. Once t-tubule membrane has been repolarised, Ca2+ channels in SR close. Once Ca2+ release from the SR stops, net Ca2+ uptake into the SR occurs and Ca2+ comes off Troponin-C so tropomyosin again blocks myosin binding site and actin .

Epithelial cell-junctions (apical to basal)

In many epithelia, cell-cell junctions are typically arranged as an apical junctional complex containing a Tight Junction nearest the apex, then an Adherens Junction just below it. Desmosomes (spot adhering junctions) are often scattered throughout the lateral membrane. Other important junctions are Gap Junctions, which act as regions of direct communication between adjacent cells

Apical Junctional Complex of simple epithelia

In many epithelia, cell-cell junctions are typically arranged as an apical junctional complex containing a tight junction (TJ) nearest the apex, then an adherens junction (AJ) just below it. Desmosomes (spot adhering junctions) (Des) are often scattered throughout the lateral membrane. Other important junctions are gap junctions, which act as regions of direct communication between adjacent cells

Cell turnover in epithelia

In many epithelial tissues, cells turnover consistently, such that the whole cell population is replaced over relatively short periods. Small intestinal epithelia turnover every 3-5 days. Colon epithelia turnover every 5-7 days. Epidermis (epithelium of the skin) turnover 48 days, but can depend on the region

In the small intestine, where are the stem cells that renew the cells during normal turnover of the epithelium found?

In the mid-region of the crypts of Lieberkuhn. NOT the base of the crypt

Where are microfilaments most dense in the cell?

In the periphery of the cell.

Transporting epithelium

In transporting epithelia, the plasma membranes contain high concentrations of ion transporters. Typically, mitochondria are closely associated with extensive basal membrane infoldings, providing energy for active transport across the abundant membranes. The infoldings increase the amount of basal membrane that can pump ions and water. The basal membrane has several folds which gives the cell a much larger surface area. · The basolateral membrane is full of ion transporters. ATP for this process comes from the mitochondria. · Sodium is pumped out at the basal side. Hence, sodium and water can be drawn into the apical membrane via passive channels. If you inhibit ATP production - you get a swelling of the apical part of the cell because you're set up for passive transport in at the apical membrane but it is not matched by active transport out at the basal membrane. · Polarity is very important for this function.

How does an increase in the frequency of stimulation of skeletal muscle lead to an increase in force?

Increased stimulation causes an increase in Ca2+ release, which means more crossbridges are attached and more force is produced.

What forms mechanical links between individual cells in cardiac muscle?

Intercalated discs

What does basal lamina underneath epithelium lie on top of?

Interstitial connective tissue and extracellular matrix (ECM)

How can secretory epithelia in glandular tissues can be arranged?

Into tubules and ducts of varying complexity.

what is the general structure of elastin?

It consists of a hydrophobic region and an alpha-helical region

Which condition affects receptors: Lupus, rheumatoid arthiritis, multiple sclerosis or myasthenia gravis?

It's myasthenia gravis - affects nicotinic acetylcholine receptors. Lupus = antibodies attack membrane areas. Arthiritis = synovial joint. Multiple sclerosis = myelin

What is the main component of hair, nails and the epidermis of the skin?

Keratin. Keratin is one of a family of fibrous structural proteins that protects epithelial cells from damage or stress. It contains many cysteine residues allowing formation of disulfide bonds. In nails, the keratin is hardened and densely packed. Albumin is the most abundant plasma protein.

what type of epithelial usually constitutes protective epithelia?

Keratinisng + non-keratinising stratified squamous

Congenital Muscular Dystrophy is caused by mutation in what molecule?

Laminin 2 (a2 chain)

Epidermolysis bullosa is caused by mutation in what molecule?

Laminin 5 (in all 3 chains)

Which substance consists of three chains, one each of an α, β and γ chain, forming a cross-shaped molecule?

Laminins are basement membrane glycoproteins. They can interact with cell surface receptors and associate with other basement membrane proteins. They regulate tissue differentiation, cell migration etc.

what are the three types of hair?

Lanugo - long wispy hair unpigmented, in fetus/premature baby and anorexics Vellus - hairs on body - unpigmented wispy hair Terminal hair - thick hair on scalp and beard, under the arms (axillary), pubic hair

What orientation is the fibrillar collagen?

Left-handed

Example of simple cuboidal epithelium

Lining kidney collecting duct and many other ducts

How would you best describe proteoglycans?

Long, linear, highly charged polysaccharide covalently linked to protein core

How does lymph fluid return to the circulation?

Lymph fluid returns to the circulation in nodes (50%) or in the lymphatic ducts in the subclavian region (50%) - just below clavical.

What's involved in covalent cross linkages in collagen?

Lysine and hydroxylysine

Hyponatremia - very low sodium concentration (often caused by fluid overload). Results in severe headaches and seizure (1-2% of people). Main cell type affected and main cell type responsible?

Main cell type affected is involved in communication = overactivity of neurones --> brain overactivity --> epileptic seizure. In hyponatremia, because low sodium concentration outside, water is driven into cell. The cell-type most responsible for water movement in the brain which could cause cerebral oedema is astrocyte - takes on bulk of water. Astrocytes are what protect neurones and maintain homeostasis.

growth of nail plate

Matrix produceds nail --> nail plate. If problem at top --> problem with nail surface. If problem at bottom --> problem with bottom of nail

Melanocyte function

Melanocytes - make melanin, help protect dna of keratinocytes from uv damage, when skin is exposed to uv it causes keratinocytes to produce melanocyte stimulating hormone, has paracrine effect on melanocytes to produce melanin. Melanocytes make it and package it in melanosomes, which travel down dendritic processes, taken up by keratinocytes and put around nucleus to protect them from dna damage. melanin causes skin pigmentation - so light skinned people get darker after sun exposure. In darker skin people it's not because of more melanocytes it's because more melanin via increased melanosomes.

What to do if have nail melanoma?

Melanomas on toes have poor prognosis ---> often spread and lead to death. So if someone has nail melanoma amputate toe usually. N.B. not all nail melanomas are pigmented

Mitotic spindle is formed by which skeletal component?

Microtubules

Which organelle type is abundant in the cells of a fluid transporting epithelium?

Mitochondria

What two forms can microfilaments come in?

Monomeric (g-actin) or filamentous

Where are most GAGs synthesised? (for proteoglycans)

Most GAGs are synthesized and attached to their core proteins in the ER and Golgi HOWEVER Hyaluronan is unique and has no core protein (simple carbohydrate chain)

Myosin crossbridges act as interdependent force generators. True or false?

Myosin crossbridges act INDEPENDENTLY of each other.

How neurones and neuroglia come together?

NO SAME: Neurone o Excitable cells of the CNS o Responsible for electrical transmission · Oligodendrocyte o Glial cell - produces myelin in CNS .Schwann Cell - myelin producing cells of the PNS · Astrocyte o Most abundant cell type in the CNS; support cells (homeostasis (neurotransmitter release and uptake), immunity, BBB, repair) · Microglia o Neuronal macrophages (immune) · Ependymal Cells Epithelial cells lining ventricles (regulate production and movement of CSF)

Is a raised lunula normal?

NO.

Pic of squamous epithelium

NOTE: Cervical smear tests sample the surface cells of the non-keratinising stratified squamous uterine cervix epithelium. Cells sampled by mild scraping, spread on a microscope slide--> stained and examined. Abnormal cells can indicate serious pathology

Nail anatomy

Nail Body (plate), Eponychium (cuticle), hyponychium, matrix (nail bed), root, germinal matrix The nail matrix contains dividing cells which mature, keratinize and move forward to form the nail plate. The nail plate has a thickness of 0.3-0.5mm and grows at a rate of 0.1mm /day for the finger nail. Toenails grow more slowly. The nail bed which produces a small amount of keratin is adherent to the nail plate. The adjacent dermal capillaries produce a small amount of pink colour of the nail; the white lunula is the visible part of the the matrix. The hyponychium is the thickened epidermis that underlies the free margin of the nail.

hyponychium

Nail itself = nail plate, which is formed by nail matrix (nail bed), which is underneath the proximal nail fold. Lunula - pale area where matrix is . Cuticle (eponychium)- seal to prevent bacterial infection and irritants. Proximal nail fold by lunula, lateral nail fold is by side of nail. Hyponychium = Skin between the free edge and fingertip of the natural nail- epidermis of nail bed

Does smooth muscle have troponin?

No, calcium binds to calmodulin. Hence, activation involves calmodulin and myosin light chain kinase, not troponin.

Does exchange of substances occur transcellularly through the endothelium?

No, the exchange of substances through the endothelium occurs via pores between cells, not through cells (transcellularly).

Can ribosomes be found on Golgi Apparatus?

No. GA is a smooth structure

Is melanin secretion a function of the skin?

No. Melanin is a pigment found in the epidermis but is not secreted.

Can microfilaments singly produce muscular contractions?

No. Myosin is an accessory protein that is required in muscular movements, it functions together with actin.

Action potentials are non-decremental. What does this mean?

Non-decremental means that the size of an action potential is maintained throughout transmission

Picture summarising collagen biosynthesis

Normal pathway of synthesizing proteins 3 alpha chains come together to form procollagen EXCEPT Alpha chains are synthesized as longer precursors by BOUND ribosomes on ER Pro-alpha chains then undergo series of covalent modifications Triple-helical pro-collagen THEN secreted from cell AFTER SECRETION Extracellular peptidases remove the propeptides (N and C regions) on the procollagen Lysine and hydroxylysine are modified when forming covalent cross-linkages Enzymes involved: Prolyl and lysyl hydroxylases Requires VITAMIN C and IRON The final helix produced in fibrillar collagen is left-handed Fibrillar collagen molecules form bonds laterally to generate fibrils Covalent cross-links providing tensile strength and stability

Which intermediate filament type forms a network in the nucleus?

Nuclear lamins form a network on the internal surface of the nuclear envelope. It helps to stabilise the envelope.

What nervous system is smooth muscle innervated by?

ONLY autonomic nervous system

What does transcellular fluid include?

Ocular, synovial and cerebrospinal fluid

Causes of oedema

Oedema - swelling of a tissue because of excess interstitial fluid · Causes: o Imbalance of forces causing fluid to move between the: · Blood Plasma · Interstitium · Lymphatic Vessels o This causes an increased permeability of capillary walls to plasma proteins. Lymphatic capillaries collect interstitial fluid, which is destined for return to the blood circulation. As lymph vessel has much lower pressure, fluid flows into them The lymphatic system returns interstitial fluid to the blood circulation. When the leakage of plasma into the interstitium exceeds the capacity of the lymphatics to collect and return it to the circulation - fluid accumulates in the interstitial space resulting in swelling (oedema)

On which face of the rERs are ribosomes studded?

On the outer face of rERs

Tracheal epithelium

On their apical surface are fibrous projections that are much larger than the brush border of the intestine: these are cilia. Interspersed among the ciliated cells are goblet cells (with this stain they are purplish). Goblet cells produce mucus which lines the airway and protects it from drying out. The cilia beat to move the mucus up towards the back of the mouth so that the mucus doesn't accumulate. Some cells don't stretch all the way to the luminal surface of the epithelium. This type of epithelium is referred to as pseudo-stratified because the nuclei look as if they are arranged in layers. It is not actually stratified because all of the epithelial cells have their base attached at the basal lamina. Overall this epithelium is referred to as a "PESUDO-STRATIFIED COLUMNAR CILIATED EPITHELIUM".

Difference between oligodendrocyte and schwann cell?

One oligodendrocyte myelinates many axons in CNS One schwann cell myelinates one axon in the PNS

What two things does movement of water depend on?

Osmosis moves water towards an area of higher osmolarity BUT this is not the whole story: membrane permeability is also crucial.

Relationship between water movements and osmolarity?

Osmosis moves water towards the area of higher osmolarity and can change cell volume.

What disease is caused by excessive ECM loss?

Osteoarthritis: . Erosive disease resulting in excessive ECM degradation . Cushioning cartilage properties lost . Aggrecan cleaved by aggrecanases and metalloproteinases . Lost in synovial fluid

Outline the 4 epidermis layers and their components

Other cell types in the epidermis include the melanocyte (involved in the production of melanin), Langerhans cell (antigen presenting cell) and Merkel cell (involved in sensation).

Hair structure

Outisde to inside: cuticle --> cortex --> medulla. Macroscopically, there's ONLY medulla on terminal hair, not lanugo or vellus. All three have cortex and outer cuticle. Genetic defects in certain keratin genes leads to disorders in skin, hair and nails

Where are sebaceous glands found?

Over the entire body, except palms and soles. Not much hair coming out of it (its vellus hair)

Basement membrane zone

Overall: lots of proteins involved in sticking the epidermis onto the dermis Epidermolysis bullosa = if one of proteins is detective --> shearing of epidermis off the dermis in minor trauma and causes blistering in severe form. Often try to repair itself, but leaves scars and ulcers. Dies in 20s due to skin cancer from inflammation. Rare condition: genetic disorder that affect proteins. Only 60-70 in UK. Bullous pemphigoid - auto antibody formation (antibody is made against one of the proteins in the basement membrane) --> blister formation. Acquired not genetic, in older people. Quite common. Do biopsy to see. Treat with steroids (topical and systemic) to suppress immune system

Cardiomyocytes

Pacemaker cells o Sinoatrial (SA) node: small, 'empty', spindle shaped cells, spontaneously active o Atrioventricular (AV) node: spindle-shaped network of cells located at base of right atrium Conducting fibres o Bundle of His: fast conducting cells adjoining the AV node & Purkinje fibres Purkinje fibres: large cells that rapidly conduct electrical impulses

Example of intercellular signalling

Pancreas to liver to maintain glucose levels

What are the three layers of dermis?

Papillary dermis, reticular dermis, hypodermis (top to bottom) Pink strandy fibres = collagen fibres Cell nuclei in dermis layer- mainly from fibroblasts with a few inflammatory cells Underneath this is sweat glands and hair follicles

What is the arrangement of collagen fibres in tendon?

Parallel bundles of collagen fibres in the tendon. Resist tensile force in one direction

Analysing graph

People in group C have lowest beta-cell volume and they have medical condition - it is T2D. It is not T1D because the fact that graph is comparing obese and lean hints towards T2D. Study shows that individuals with T2D have dysfunction within beta cells in pancreas, less able to produce insulin - so not just that insulin is less effective but also that less insulin is able to be produced Stars at the top of the bars represent significant difference

What enzyme is involved in the relaxation of smooth muscle by removing phosphate from myosin?

Phosphotase

Physiological response to hyperglycemia

Physiological response: o Insulin is secreted by the beta cells in the islets of Langerhans in pancreas o Glucose uptake, reduced glycogenolysis, reduced glyconeogenesis o Insulin has PARACRINE effects: (hormone acts on adjacent cell) ○ It inhibits glucagon secretion by nearby alpha cells o Insulin also has ENDOCRINE effects on liver cells Other examples of paracrine signalling: · Nitric oxide produced by endothelial cells in blood vessels causes vasodilation · Osteoclast activating factors produced by adjacent osteoblasts

How similar are blood plasma and interstitial fluid in composition?

Plasma is very similar to interstitial fluid except plasma has MORE protein. Both are extracellular fluids

Epithelial polarity - secretion

Polarity is needed to ensure that the secreted products are delivered to the correct tissue compartment. You don't want to be secreting things in the wrong direction e.g. into the extracellular matrix which could cause damage.

What do hair and nails have in common?

Protein (Keratin) product of the hair follicle (mini-organ) & nail matrix

How does protein content differ between intracellular fluid and extracellular?

Protein content is higher in intracellular fluid

Keratin filaments

Proteins that form filaments --> supercoil to form bigger filaments --> group together to form strands, which are strong to make up natural fibre of hair Different types of keratin: genetic defects in certain keratins cause genetic syndromes in hair, skin and nails. E.g. epidermolysis bullosa simplex

What types of curvature is normal in nail?

Proximal to distal curvature and Lateral to medial curvature If the angle EXCEEDS 180 degrees, then this is clubbing which may indicate disease. The nail is curved in 2 planes and has longitudinal ridges in a proximal to distal direction.

Ribosome structure

Ribosomes are composed of two distinct subunits, each of which contains ribosomal RNA (rRNA) and protein. read messenger RNA (mRNA) to synthesise polypeptide chains Prokaryote = 70s (50s + 30s) Eukaryote (80S) = 60s+ 40s Mammalian mitochondrial= 55s (39S+28S)

Stratified squamous epithelium

STRATIFIED = lots of layers of cells · The cells have a variety of shapes - they are quite cuboidal near the basal lamina and quite flat at the surface. · Squamous classification related to the surface cells · Two Main Types of Squamous Epithelia: o Keratinizing - e.g. epidermis (skin epithelium) (nuclei NOT VISIBLE in the surface cells) Non-Keratinizing - e.g. linings of mouth (exactly the same but the nuclei are visible in surface layer cells)

What are the functions of basement membranes?

Separating cells from connective tissue

Draw a nucleus

Showing: pore in nuclear envelope, nuclear envelope, chromatin, nucleolus, nucleoplasm, inner membrane, outer membrane

Function of the three types of muscle

Skeletal muscle: is attached to bone and produces movement of the body relative to the external environment. Cardiac muscle: pumps blood around the body through the blood vessels. Smooth muscle: exists within the lining of all the hollow organs (e.g. blood vessels, gastrointestinal tract) and provides the propulsion to move substances within the body.

Example of stratified squamous epithelium

Skin epidermis (keratinising) - nuclei not visible in surface cells Lining mouth and oesophagus(non-keratinising)- nuclei visible in surface layer cells

Skin epithelium (epidermis)

Skin has to be waterproof to prevent the cells below drying out and dying. The surface cells of the epithelium have died ("cornified") leaving only the dense network of their keratin containing intermediate filaments to form a non-cellular protective layer that absorbs oily secretions to become waterproof. The epithelium of the skin is the epidermis. This is a STRATIFIED SQUAMOUS epithelium of similar organisation to that of the oesophagus, but important differences are apparent. The cells of the epidermis are called KERATINOCYTES. The most basal layer is the STRATUM BASALE, a single layer of CUBOIDAL cells in this layer produce new cells that form the upper layers that differentiate and ultimately replace the cells being lost from the surface. The MELANOCYTES, which provide pigment granules to the keratinocytes, are found in this layer. The layer just apical to the stratum basale is the STRATUM SPINOSUM. In this region, The cells form a few layers of cells which often have a spiky appearance. The region apical to this is the STRATUM GRANULOSUM. The cells in these layers contain numerous granules, which may not be visible in the specimen. The apical layers, the STRATUM CORNEUM, are layers of dead cells that have been "cornified" (keratinised) during the differentiation and turnover of the epidermis. Nuclei cannot be observed in the cells of the stratum corneum. In thin skin , hairs and their follicles are present. In thick skin (found on the palms of the hand and soles of the feet) hair is not present, and the stratum corneum is typically many times thicker than in thin skin. Overall: stratum basale, stratum spinosum, stratum granulosum, stratum corneum

Which organelle type is abundant in the cells whose main function is secreting hormones?

Smooth endoplasmic reticulum

examples of smooth muscle

Stomach and blood vessels

What type of cells usually form protective epithelia?

Stratified squamous. can be keratinising (cells of the upper (surface) layers are "dry", because the cells have hardened and died; their nuclei are not visible) or non-keratinising ( the upper (surface) layer is "wet", because the cells are alive; their nuclei are visible.)

How are the layers of collagen arranged?

Successive layers perpendicular to each other Allows tissue to resist tensile strength in all direction

What are the point of t-tubules in the sarcolemma?

T-tubules are finger-like invaginations of the sarcolemma (surface membrane). T-tubules (Transverse tubules) allow depolarization of the membrane to quickly penetrate to the interior of the cell.

What is transcellular fluid? What is interstitial fluid?

TCF: Fluid contained within epithelial lined spaces - smallest component of ECF. It is special relatively isolated fluid compartments outside cells, with a controlled composition and not in equilibrium with other extracellular compartments. IF: fluid that surrounds and bathes tissues - largest component of TCF

How many types of enzyme-linked receptor are there?

THERE ARE THREE TYPES OF ENZYME LINKED RECEPTOR 1) Tyrosine Kinase Linked Receptor (98%): oErbB receptor - · Big family of receptors · Ligand: Epidermal Growth Factor, Transforming Growth Factor b Physiological effect: cell growth, proliferation o insulin receptor: · Ligand: Insulin Physiological effect: glucose uptake and reduce glucagon secretion from alpha cells 2) Guanylyl-cyclase Linked Receptor . NPRA: · Ligand: Atrial/Brain natriuretic peptide Physiological effect: Vasodilation, decrease in blood pressure 3) Serine-Threonine Kinase Linked Receptor: .TBR1 · Ligand: Transforming Growth Factor b Physiological effect: apoptosis

Which protein the major component of the mitotic spindle?

TUBULIN NOT MICROTUBULES. Microtubules form the mitotic spindle. But "microtubule" is a structure, not a protein. Microtubules are made of the protein tubulin, thus tubulin is the answer instead of microtubules.

How does isometric contraction fit in with sliding filament theory?

Tension-Load Relationship · Isotonic Contraction: o Tension > Load o Muscle contracts and the fibres shorten · Isometric Contraction: o Tension = Load o You get actin being pulled in and out o You still use ATP because it is needed to return myosin heads to the charged state

What is the extent of stretching limited by?

The 'interwoven-ness' of the elastin molecules. NOT the length of the molcules

What happens to H zone as thin filaments are brought closer together?

The H zone gets SMALLER as the thin filament are brought closer together during sarcomere shortening.

Picture showing how cells look in stratum basale, spinosum, granulosum and corneum

The Stratum basale is the deepest layer and cells have large nuclei and dense cytoplasm. The Stratum spinosum is next, and is characterised by intracellular spines seen upon microscopy. The cells of the Stratum granulosum layer have granules containing the precursor of filaggrin (which help bind keratin filaments). The staining of these granules helps to identify this layer upon microscopy. The most superficial layer is the Stratum corneum which contains dead, flattened cells filled with keratin.

Observable features of epithelia

The cells are lined up in a single layer, with their nuclei alongside each other. This is known as a simple epithelium. The base of each cell is attached to a thin fibrous layer which is only just detectable in the light microscope, called the BASAL LAMINA or BASEMENT MEMBRANE. Attachment to a basal lamina is a characteristic feature of epithelia. The majority of cells are identical with a pink staining cytoplasm. The cells are taller than they are wide and are described as columnar. Their function is absorption of the products of digestion of food (for example, monosaccharides and amino acids) and they are known as instestinal absorptive cells or ENTEROCYTES. Interspersed among them are cells with a very pale cytoplasm and a bulbous shape. They are mucus-secreting cells known as GOBLET cells. The apical surface of the enterocytes (the one facing the lumen of the intestine) is specialised for absorption by the presence of a BRUSH BORDER. This can be seen as a zone without organelles at the apical surface of the epithelium. It consists of a close packed row of small finger-like projections of membrane which serve to increase the available surface area. Because they resemble villi in shape and function but are about 1000 times smaller they are known as microvilli. There is no brush border on the rest of each enterocyte (what is called the basolateral surface). It is characteristic for epithelial cells to be polarised, that is to have two surfaces with different properties. No gap is visible between adjacent cells, and if any existed there would be diffusion of undesirable contents of the lumen into the rest of the body. Another characteristic of an epithelium is the presence of JUNCTIONS between adjacent cells.

If you treat mammalian cells with a drug that inhibits the Na+/K+ exchange pump, what will be the effect on cell size?

The cells will swell significantly

What is the nail cuticle position and function?

The cuticle/eponychium ensheathes the nail plate from both above and below. It acts as a barrier to the external environment.

Which part of the nail can lead to permanent nail deformities when damaged?

The distal end of the matrix is seen as the lunula (half-moon). This area is critical to the proper growth of the nail plate.

How long does an action potential last for?

The entire action potential lasts only a few milliseconds (1 millisecond = 0.001 s)

Cell turnover in the epidermis

The epidermis is the keratinising stratified squamous epithelium of our body surface Surface cells are constantly being lost, but are replaced by new cells being formed in the basal layer which migrate up while undergoing a programme of differentiation that eventually leads to them flattening out and keratinising. Each layer replaces the one above as the layers are lost from the surface. How this links to a callus:You are applying pressure and abrasion to areas of the skin. This stimulates the cells to divide more rapidly, and the rate of loss from the surface is less than the rate of new cell production, so there is an increase in tissue mass. Your skin is adapting to a change in its circumstances.

Proteoglycan families

The families that proteoglycans are categorised into are based on structural and functional characteristics. · Basement Membrane e.g. perlecan · Aggregating (interact with hyaluron) e.g. aggrecan · Small Leucine-Rich e.g. decorin · Cell Surface e.g. syndecans 1-4

Tight junctions in human gastric epithelium

The localisation of TJs in an epithelium show that, while E-cadherin is present along the whole of the lateral plasma membrane, the TJ protein, occludin is confined to the apical lateral membrane.

What is the position and function of the nail bed?

The nail bed produces a small amount of keratin and is adherent to the nail plate.

What occurs at nail root?

The nail root is where the nail growth begins. It is embedded underneath the skin at the base of the nail.

Compare pH inside vs outside cell

The pH is roughly 7.4 in plasma vs. 7.1 intracellularly (twice the [H+].

Collagen helix structure

The three a chains form a STIFF TRIPLE HELIX · Each a chain forms a helix and each helix wraps around each other. · Three a chains form a STIFF TRIPLE HELICAL STRUCTURE. · Every third position must be a GLYCINE - this is the only amino acid small enough to occupy the interior of the triple helix. · Characteristic repeat: gly-x-y ( x is often proline, y is often hydroxyproline) · In fibrillar collagens - each a chain is ~1000 amino acids - forming a left-handed helix.

Cartilage in trachea

The trachea is surrounded by a series of C-shaped cartilage rings that keep the airway open. The support cells of cartilage are called chondrocytes (have blue staining nuclei), and they are well separated from each other. They each lie in their individual pale staining regions, called lacunae. The remaining space, staining purple, is the ECM of the cartilage. You will find it difficult to see evidence of the structure of the ECM since the dense fine network of collagen fibres and the glycosaminoglycans rich in sulphated sugars produce a fairly homogenous appearance in this type of cartilage which is called hyaline cartilage. Other types of cartilage have modified ECMs. Fibrocartilage contains thicker collagen fibres oriented to provide tensile strength in a particular direction, for example in the pubic symphysis (joint connecting the two halves of the pelvis at the front) or the intervertebral discs (connecting adjacent vertebrae of the spinal column.) Elastic cartilage contains additional elastic fibres to provide pliability and resilience (for example in the external ear). Cartilage is unusual in that it has no blood vessels and substances reach the chondrocytes by SIMPLE DIFFUSION through the ECM - despite the solid appearance of cartilage, it consists of about 70% water.

After the neurotransmitter is released from the pre-synaptic knob, where does it go?

The transmitter diffuses through the interstitial fluid and binds to receptors on dendrites or the cell body of neighbouring neurones.

Urinary Epithelium (Transitional)

The urinary epithelium has certain features of both stratified and pseudo-stratified epithelia (and is sometimes called a transitional epithelium). It is specialised to be highly impermeable to urine and to be able to stretch as the bladder fills.

How many types of collagen are there?

There are at least 28 types of collagen which occur in different tissues. Although these have distinct properties they all have the same triple helix structure which is the special feature of collagen.

Why is fibronectin considered essential for life?

There are no known mutations of fibronectin in humans

What is Meissner's corpuscle?

They are a type of nerve endings in the skin that are responsible for sensitivity to light touch.

Mesentery

Thin layer of epithelial tissue that attaches parts of the intestines to the rest of the body. It allows the whole length of the intestines to be folded up to fit within the abdominal cavity but still have a connection carrying its blood and nerve supply, and it means that the intestines can be somewhat mobile during peristalsis. Parts are very thin - just a sheet of tissue viewed edge on - while in other places there are blood vessels (tubes containing obvious red blood cells) surrounded by fat which looks very pale under the microscope. The epithelium is only one cell deep (aka simple). Although cannot see the cell boundaries, can guess roughly where they are since they will lie between nuclei. Epithelium surrounding the mesentery is described as a SIMPLE SQUAMOUS EPITHELIUM. Functionally, this epithelium is simply forming a boundary. There is no need for a more elaborate epithelium since the cells do not have other functions like absorption or secretion.

When desmosomes go wrong...

This severe blistering, which also affected the mouth and anus, was the result of loss of function of desmosomes. This person started making auto-antibodies to desmosomal cell-cell adhesion molecules, and these reduced desmosome adhesion to make the epidermis fragile. Desmosomes mechanically link cells to each other and the ECM (via hemidesmosomes) This arrangement provides mechanical stability to tissues including epithelia and cardiac muscle. Desmosomes are abundant between the cells of STRATIFIED SQUAMOUS EPITHELIUM. If desmosome function is compromised, these epithelia become fragile and easily damaged.

How to describe connective tissue including ECM and cell distribution?

Tissues rich in extracellular matrix with sparse cells.

What is tonicity?

Tonicity defines the 'strength' of a solution as it AFFECTS FINAL CELL VOLUME Tonicity depends on both: · Cell membrane permeability . Solution composition

Basic microanatomy of skin

Top layer: Epidermis, then dermis, then subcutaneous tissue Within skin also have hair follicles aka pilosebaceous units (because have hair, hair follicle and piloerector muscle) Within dermis - blood vessels and nerves Between epidermis and dermis have basement membrane Hair within hair follicle and sebaceous gland makes sebum (oil), eccrine gland makes sweat

Hair follicle structure

Top to bottom: Infundibulum - from where sebaceous gland joins to surface Isthmus - from there to where arrector pili muscle joins Suprabulbar- area till bulb Hair bulb - where hair shaft is produced, specialised site where melanocytes are there and give pigmentation to hair, blood vessels, nerves and specialised germinal epithelium

during an action potential, Ca2+ is simultaneously released and transported back into the sarcoplasmic reticulum. True or false?

True

Myelin surrounds neuronal axons in peripheral and central nervous system. True of False?

True - myelin surrounds neuronal axons in PNS and CNS

ASSERTION: Tensile strength and stability of connective tissues is provided by covalent cross-links between collagen molecules REASON: Collagen contains lysine and hydroxylysine residues that are capable of forming covalent cross-links.

True, true - reason is correct explanation

ASSERTION: Articular cartilage resists compression REASON: Articular cartilage contains collagen II fibrils.

True, true - reason is not correct explanation

Role of junctions in epithelial polarity

Two types of junctions - belts (zonula) and spots (macula). · As far as polarity is concerned, the TIGHT JUNCTION is one of the key players. · It's a very close point of contact between adjacent cells. This prevents material passing between the cells. · The tight junctions block the PARACELLULAR PATHWAY. · If the paracellular pathways is blocked, any passage across the epithelium must be through the cell. Therefore the cell has the opportunity to control passage.

Alport's Syndrome is caused by mutation in what molecule?

Type IV Collagen (a5)

Example of non-fibrillar collagen

Type IV collagen - forms networks. Type 1,2,3 are fibrillar

What amino acid do tyrosine kinases phosphorylate?

Tyrosine lol

What is used to stain skin in histology?

Use H&E stain = haemotoxylin and eosin

What size are the vesicles formed from golgi apparatus?

Vesicles budding from it usually contain macromolecules and are 50nm or larger

How do melanocytes and langerhan cells interact with keratinocytes?

Via dendritic processes (long legs of dendritic cells)

How can infectious agents affect the turnover of epidermis?

Warts = result of infection of the epidermal keratinocytes by one of the family of human papilloma viruses. The virus hijacks the cell proliferation machinery and increases cell proliferation.

Epithelial polarity - transport

We need epithelial polarity to give directional flow. Without directionality, there would be an even distribution of transporters so there would be no net directional flow. In ion and fluid transporting epithelia, ion pumps and channels have apical-basolateral polarisation in the plasma membrane, i.e. its activity is restricted to only some parts of the plasma membrane. This configuration allows directional flow.

Molecules that transport across membranes

When considering a synthetic lipid bilayer which doesn't have any membrane proteins: · Hydrophobic Molecules - can easily pass through the membrane e.g. gases and steroid hormones · Small Uncharged Polar Molecules - some molecules will diffuse through but the majority do not. E.g. h20, urea, glycerol · Large Uncharged Polar Molecules - almost all molecules don't pass through the membrane .e.g glucose, sucrose Ions - do not pass through the membrane

Synchronicity in hair cycle

When hair is growing through the three phrases, are growing out of sync with each other. When baby is born however it is all synchronised and that explains why baby's born with head of hair, then sheds and starts growing again. Post birth, hairs become non-synchronous. Time in anagen is variable across different bodily sites. telogen effluvium - thinning of hair due to early entry of hair into telogen phase. Aetiologies include emotional as well as physiological stress (hypothyroidism, sepsis and anemia).

Oedema mechanisms

When the leakage of plasma into the interstitium exceeds the capacity of the lymphatics to collect and return it to the circulation - fluid accumulates in the interstitial space resulting in swelling. Can be caused by variety of mechanisms - o Inflammatory oedema: Inflammation around the site of the insect bite causes local blood vessels to become leaky. Swelling occurs because the rate of leakage from the vessels is greater than the rate at which the lymphatics can drain it. o Hydrostatic oedema: Overweight man likely to have high blood pressure, which means increased hydrostatic pressure in vessels. This pushes more fluid out of the vessels, and can lead to accumulation of interstitial fluid. o Compromised function of the lymphatics: · The breast cancer survivor is likely to have had axillary (armpit) lymph nodes removed as part of her diagnosis/treatment. This can remove the pathway of drainage from the upper limb on the affected side, resulting in the accumulation of fluid. · In elephantiasis, parasitic worms can block lymph vessels, thereby preventing lymphatic drainage. In this case, the lymphatics in the right groin region will have been blocked, preventing the drainage of interstitial fluid from the right lower limb

What diagnostic test picks up bone density?

X-rays can pick up density of bone, how long it's been mineralised for. Can see differences in density after fracture.

Fungal nail infection

Yellow nail syndrome - diagnosed on basis of appearance, rare. Onset of 40s or 50s, with lung/sinus disease and yellow nails:

Do rER and sERs come into physical contact?

Yes

Are cardiac cella and smooth muscle cells spontaneously active?

Yes, they are spontaneously active (with myogenic contractions not requiring innervation).

Can ECM affect cell differentiation?

Yes.

Telogen Effluvium

a cause of hair loss: • Premature termination of anagen -->Telogen • Diffuse Hair Loss • Many causes - illness, trauma, pregnancy Regrowth over 3-6 months. Ongoing stress can cause longer duration

Tissue definition

a group of cells whose type, organisation and architecture are integral to its function. Tissue = Cells + Extracellular Matrix + Fluid

What do microfilaments associate with?

adhesion belt

What does hyaline cartilage consist of?

aggrecan aggregates - consist of aggrecan (GAG chains = keratan sulfate and chondroitin sulphate) associated with hyaluronan and a link protein

Apical, basolateral meaning

apical - at lumen basolateral - outside - in contact w/ ECM

What two types of roles does ECM play?

architectural (mechanical stability) and instructional roles (influences cell behaviour)

Main purpose of epidermis

barrier function to skin. Part of barrier is the keratin protein. Epidermis makes keratin: as keratinocytes mature and differentiate they make keratin in the stratum cornea

What separates dermis and epidermis?

basement membrane

What is salbutamol?

beta 2 agonist

What's within the dermis?

blood vessels and nerves

what makes up central nervous system?

brain and spinal cord. within brain there are 4 cerebral hemispheres: Cerebral hemispheres - highly convoluted surfaces of ridges( gyri) and valleys(sulci) 4 functional regions of cerebral cortex o Frontal - front o Occipital - back o Temporal - side · Sound and speech recognition o Parietal - middle top · Sensory and motor function (proprioception) o There are lots of fold - there is lots of white matter so the brain folds up to make sure that it can fit in the cranium. · Gyri - ridges · Sulci - valleys

Example of pseudostratified columnar epithelium

bronchi and trachea epithelium

What is z-line made of?

capz and alpha-actinin

What cancer can keratinocyte form?

carcinoma

Kiss points on tight junctions

close contacts (focal connections, "kiss points") between adjacent cells' plasma membranes; these contacts are parts of the TJ strands. Closely interact with their counterparts on adjacent cells to form the sealing strands Paracellular = between cells. Transcellular = through cells

osteogenesis imperfecta is caused by mutation in what molecule?

collagen type 1

Which substances are found in basement membrane?

collagen type IV, perlecan, laminin

What does the dermis contain?

collagen, elastin, GAGs, fibroblasts, immune cells

Peroxisomes info

contain enzymes involved in lipid and oxygen metabolism e.g. catalases, peroxidases. Spherical and contains Paracrystaline core of oxidase and catalase enzymes. The enzymes present in peroxisomes can be present at such high concentrations that they "crystallise" to form the cores that are observed in transmission EM. These organelles are important in oxidation reactions. A by-product of many of these actions is peroxide, which is used in peroxidation reactions in many cell types.

Zonulae

continuous belts

What are intermediate filaments usually connected to?

desmosomes

Maculae

discrete spots

What does the nail matrix contain?

dividing cells which mature, keratinize and move forward to form the nail plate. The matrix can also contain melanocytes

Disorders of myelin

e.g. multiple sclerosis - diff to move + transmit signals

Secretory tissues

e.g. pancreas · The pancreas has both exocrine (into duct/lumen) and endocrine (into bloodstream) secretory functions. · Exocrine = apical ---> duct Endocrine = basal ---> circulation

Where is the epidermis derived from?

ectoderm

What is the core of elastin made of?

elastin, fibrillin and microfibrils

Example of simple columnar epithelium

enterocytes (lining small intestine), and many other absorptive and secretory epithelia

Layers of skin

epidermis (stratum corneum, granulosum, spinosum, basale), dermis (papillary, recitular, hypodermis)

Different intermediate filaments in different cell types: epithelial, mesenchymal, neurons, muscle

epithelial cells - cytokeratin; mesenchymal cells - vimentin; neurons - neurofilament protein; muscle cells -desmin

What are the two types of melanin?

eumelanin and pheomelanin eumelanin - black/brown hair pheomelanin- in red hair. also get pale skin

excitation-contraction coupling in skeletal muscle

events that link the action potentials on the sarcolemma to activation of the myofilaments, thereby preparing them to contract 1. AP propagates along the myofibril membrane (sarcolemma) and T-tubules. 2. Depolarisation activates dihydropyridine receptors (DHPR) causing a conformational change in DHPR on sarcolemma. 3. The change in shape allows DHPR to make physical contact with Ryanodine Receptors (RyR) on the Sarcoplasmic Reticulum. 4. This leads to a conformational change in RyR which opens the RyR channel and causes Ca2+ release from the SR. OVERALL: Depolarisation ---> Increase in intracellular Ca2+

Similarities and differences between two types of intracellular receptors

example of type 1 - glucocorticoid receptor: o Ligand: cortisol, corticosterone o Physiological Effect: Downregulate immune response, increase gluconeogenesis Agonists: Glucocorticoids example of type 2- thyroid receptor o Ligand: Thyroxine (T4), Triiodothyronine (T3) o Physiological Effect: Growth & Development Agonists: Thyroid hormones

what happens in fibrotic disorders?

excess deposition of collagen - normal tissue gets replaced by collagen

Hirutism

excessive hair on body caused by excessive androgen drive Causes: • Genetic variant • PCOS • Excess androgens • Drugs - Ciclosporin

Fibrotic disorders

excessive production of fibrous connective tissue (extracellular matrix) - normal tissue gets replaced by fibrotic tissue (normal tissue is replaced with collagen) · Scar tissue replaces normal tissue in fibrosis. · Can see connective tissue/collagen fibre deposition in blue staining · In pics fibrotic tissue looks more holey Examples of fibrosis: Liver Cirrhosis, Lung Fibrosis (silicosis), diabetic nephropathy

What is exocrine and endocrine secretion?

exocrine (into a duct or lumen) and endocrine (into the bloodstream)

What molecules are leukotrienes derived from?

fatty acids

What cell produces collagen?

fibroblast

Give wo examples of multi-adhesive glycoproteins

fibronectin and laminin

What is the cerebellum responsible for?

fine tuning motor functions and muscle coordination

For motility, what is required in addition to microtubules?

for motility, accessory proteins are required in addition to microtubule 'tracks'

Which gel-like substance makes up proteoglycans and when hydrated, resists compression?

glycosaminoglycans. GAG(s) are joined to a core protein to give proteoglycans. GAGs are long, unbranched sugars made up of repeating disaccharides.

Alopecia areata

immune cells/antibodies attack hair follicle and get patch of no hair (autoimmune). Often recover but can total hair loss (on head/whole body)

On which side of collagen is glycine found?

in the interior of all collagen molecules as it is small enough to occupy that space.

What is the result of increased filament sliding?

increased speed of filament sliding decreases number of cross-bridges able to be formed since there is less chance of attachment and less force

What is motor unit recruitment?

increasing the number of 'active' motor units. Increasing recruitment results in more force

Folliculitis

inflammation of the hair follicles can be caused by acne infections or infections Most common pathology of hair follicle Inflammation, overproduction of sebum, kertainiation within infundibulum forming a plug

Micropinocytosis

internalization of small volumes of extracellular fluid in membrane vesicles

Hyaluron aka hyaluronic acid

is a GAG (glycosaminoglycan). not proteoglycan because no core protein Features: · UNIQUE - NO CORE PROTEIN - it only has a carbohydrate chain · Synthesised in the cell surface at membrane- NOT in the ER/Golgi · UNsulfated A single long chain has up to 25,000 repeat disaccharides Hyaluron is a HUGE molecule, which occupies about the same volume as a bacterium.

Tight junction (zonula occludens)

it is a belt junction because it is a zonula - there are many point where adjacent membranes form very close contacts. · points on adjacent membranes form close contacts at apical lateral membranes · The more elaborate the networks - the tighter the seal. · These contacts are in the form of a network - they seal the paracellular pathway between cells) . · The tight junctions also segregate membranes (segregates apical and basolateral membrane polarity)- they stop proteins which diffuse through membranes - allows adjacent cells to be different and allows polarity to be established. The kiss points are a linear array which form a network of integral membrane proteins that hook up with membrane proteins on adjacent cells.

What is main cell in epidermis?

keratinocyte

Signifiacne of collagen arrangement

layers are perpendicular so resist tension in all directions

ionotropic receptors

ligand-gated ion channels · Ligand, neurotransmitter and hormone can be used interchangeably in this context. · Ligand binding --> opening of ion permeable pore traversing the membrane Process: 1) Ligand binds to the receptor protein 2) Change in conformation of channel protein --> opening of a pore 3) Pore allows ions to move in or out of cell (down concentration gradient) according to their respective concentration gradients - permeable mainly to sodium ions (influx) and also calcium ions · Example 1: Nicotinic Acetylcholine Receptor o Location: skeletal muscle at neuromuscular junctions - it begins the depolarisation which leads to muscle contraction. o Ligand = acetylcholine. o Physiological effect: muscle contraction · Nicotinic Acetylcholine Receptors can be found in the brain as well. · Example 2: GABAA o Location: many cells in the CNS o Ligand: gamma-amino butyric acid (GABA) o Physiological effect: · Allows transmission of anions · GABA binds to the receptor and causes the opening of the pore which allows an influx of chloride (Cl-) ions · GABA acting on cells will cause a depression of activity If you block the GABA receptor you get hyperexcitability of the CNS and possibly epileptic seizures

Where is peripheral heterochromatin found in the nucleus?

lines the inner side of the nuclear envelope

Demodex mite

lives inside hair follicle (esp. hair and nose), cylindrical mite, commensal (normal). Implicated in certain conditions e.g. rosacea

Head lice

long and thin. Found in school kids sometimes. If don't have modification, put loads of moisturise and suffocate them, thus causing death N.b. head and body louse look identical but are genetically different. Head louse will only go to the head and body louse only to body. Important because head louse doesn't transmit disease.

Body louse

long and thin. can transfer relapsing fever, typhus e.g. WW2 louse born typhus, only occur in war/famine - can be treated with antibiotics N.b. head and body louse look identical but are genetically different. Head louse will only go to the head and body louse only to body. Important because head louse doesn't transmit disease.

Examples of autocrine signalling

lots are negative feedback: . T-lymphocyte secreting IL-2 but also having IL-2 receptor on surface. IL-2 can bind to the IL-2 receptor on its own surface thus having an effect on the cell IL-2 can also bind to IL-2 receptor on adjacent activated T-cell · Acetylcholine binds to pre-synaptic M2-muscarinic receptors · Growth factors (e.g. TGFB) from tumour cells can lead to mitogenesis in the tumour cell When ADP is released by platelets interacted with ADP receptors on platelets and causes platelet activation and aggregation, get haemostasis and thrombosis.

Examples of simple squamous epithelium

lung alveolar (air sac) - thin for gas exchange, mesothelium, endothelium lining blood vessels

Give an example of disease caused by excess deposition of ECM

lung and liver fibrosis

Langerhan cell

macrophage (APC) specific to the epidermis

Aggrecan

major cartilage matrix constituent · The core protein of aggrecan is linked to hyaluronan · Together this makes a complex and it has a link protein which makes the structure very LARGE · Aggrecan Aggregates - the complex of aggrecan, hyaluronan and the link protein

Extracellular matrix definition

material deposited by cells which forms the insoluble material that you will find extracellularly (e.g collagen, elastin, proteoglycan)

Nail pigmentation

may indicate nail melanoma . Says something in nail matrix is making pigment - either a (mole) melanocytic nevus or melanoma . If gets dark/wider then do biopsy. Management - monitor/biopsy. Don't want to do biopsy necessarily , because then remove part of the matrix --> get bit of nail cleft.

What cancer can melanocyte form?

melanoma

Where is dermis derived from

mesoderm

Where do microtubules originate from?

microtubule organizing center (MTOC) within cell

Astrocytes

most abundant cell type in CNS Neuroglia - 'neuro glue', every other cell type in CNS that aren't neurones · Astrocytes - 'astro' like appearance · Foot processes - play important role in maintaining blood brain barrier · Outnumber neuronal cells in the CNS · NOT EXCITABLE · CAN PROLIFERATE · Functions: repair, immunity, homeostasis o Structural cells - support by acting as a 'glue' o Cell Repair - provide nutrients for repair of neuronal cells o Facultative Macrophages - immune cells and can turn into macrophages when necessary o Homeostasis - signals sent using ions. Astrocytes mop up neurotransmitter and other substances (ions) that are released within the CNS - sort of like a sponge, make sure ion balance remain same in CNS · MOST ABUNDANT CELL TYPE IN THE MAMMALIAN BRAIN

Where do melanocytes come from?

neural crest

What else are intermediate filaments found in other than cytoplasm?

nuclear lamin - on the internal surface of the nuclear envelope (provides support)

Nuclear envelope structure

nuclear pores with scaffold nucleoporins, channel nucleoporins, membrane ring proteins, nuclear basket and cytosolic fibrils

cytoplasm of nucleus?

nucleoplasm

Skeletal muscle structure

o Bundle of muscle cells called MYOFIBRES o Myofibres are: . large and cylindrical . multinucleated . packed with myofibrils o Myofibrils . light and dark bands give them striated appearance . A-band - dark bands, intersected by a darker region (h-zone) . I-band: light binds intersected by a dark line: z-line (z-disc) . z-line: made up of alpha-actinin and CapZ o Sarcomere . functional unit of muscle - lies between 2 z-lines AmericanHealthIsZilch A-lines and I-Lines gives striated colours to muscle fibres Overall: Myofibres, within this , myofibrils, within this, sarcomeres. Skeletal muscle = striated due to banding pattern. Sarcomere: functional unit of muscle, in myofibril, lies between 2 z-lines

What does brainstem consist of and what are functions?

o Consists of (Descending Order): · Midbrain · Pons · Medulla o Target or source of all cranial nerves +many functions Primarily grey matter (cell bodies)

Proteoglycans

o Consists of a CORE PROTEIN + one or more GLYCOSAMINOGLYCAN (GAG) CHAINS are covalently attached. o GAG chains and the core protein of a proteoglycan are linked via a LINK TETRASACCHARIDE · GAG chains are long, unbranched sugars consisting of a REPEATING DISACCHARIDE · GAGs occupy a large volume relative to their mass. · GAGs form hydrated gels which can be very resistant to compression

Position and function of spinal cord?

o Extends down from the medulla in the brain stem · Conduit for neural transmission Co-ordinates some reflex actions

What does cerebellum consist of and what are functions?

o Hindbrain structure attached to the brainstem o Important in fine-tuning motor function o Involved in balance and posture You can exist without the cerebellum but life will be more difficult

Gene mutations affecting ECM catabolism

o Hurler's Syndrome - L-alpha-iduronidase o Other mucopolysaccharidoses - inability to degrade GAGs (glycosaminoglycans)

· Four main groups of GAG chains:

o Hyaluron o Chondroitin Sulfate/Dermatan Sulfate o Heparan Sulfate o Keratan Sulfate

Osmosis in a membrane permeable to H20 and solute

o Initially, Osmolarity INSIDE > OUTSIDE o Osmosis: water moves down the concentration gradient into the cell o Diffusion: solute moves down the concentration gradient out of the cell - reduces intracellular osmolarity o H20 will diffuse in both directions (inwards down its conc gradient, and out as solvent gradually increases in conc outside) OVERALL EFFECT: Water concentration and solute concentration is even inside and outside the cell - no further net diffusion of osmosis (Osminside=Osmoutside) - no change in cell volume after equilibration.

3 cell types found in the epidermis and their functions

o Langerhan cells = antigen presenting o Merkel = sensation o Melanocytes = produce melanin

Structural differences between oligodendrocytes and astrocytes?

o Oligodendrocytes are smaller o Oligodendrocytes have a denser cytoplasm and nucleus o Absence of intermediate filaments and glycogen in the cytoplasm

Osmosis in membrane permeable to water but impermeable to solute

o Osmosis - water moves down the concentration gradient into the cell. o Impermeant solute can't move out . Hence water entering to reduce conc of solute is retained o Final state - Osmi may NOT be able to equilibrate with Osmo After equilibration, CELL is swollen and may BURST

Gene mutations affecting matrix proteins

o Osteogenesis Imperfecta - Type I Collagen o Marfan's Syndrome - Fibrillin 1 o Alport's Syndrome - Type IV Collagen (a5) o Epidermolysis Bullosa - Laminin 5 (in all 3 chains) o Congenital Muscular Dystrophy - Laminin 2 (a2 chain)

Cardiac muscle overview

o Walls of the heart (myocardium) --> primarily cardiac muscle o Cardiomyocytes are STRIATED muscle o Intercalated Disc: (connect the cardiomyocytes) · Specialised discs connecting individual cardiomyocytes · They have desmosomes and gap junctions · Desmosomes - hold the membrane structures together · Have many Gap Junctions - allow electrical communication between cells - allow action potentials to spread rapidly from cell to cell o Sarcomeres: • Contractile units of cardiomyocytes Mechanism of contraction is same as skeletal muscle

Osmosis in a membrane permeable to water and solute 1 but impermeable to solute 2

o Water moves down the concentration gradient into the cell until the osmolarity is the same inside and outside the cell o Solute 1 moves out of the cell down a concentration gradient and decreases intracellular osmolarity o Impermeant solute can't cross the membrane, hence h20 entering to reduce concentration of solute 2 is retained o After equilibration, CELL SWELLS - increase in cell volume Overall, Osmi = Osmo, H2O conc equal, Solute conc equal. No further net diffusion, or osmosis.

What are microtubules made of and what is the diameter of a microtubule?

o alpha and beta tubulin o 20nm

Descirbe the link between fibronectin and the intracellular compartment

o associates with an integrin via RGD motif which associates with actin - forms a mechanical continuum with the actin cytoskeleton o the fibronectin is also bound to collagen

What is the diff between axons and dendrites?

o axons are myelinated, dendrites are not o one axon but many dendrites

Describe three roles of fibronectin

o binding to integrin and linking ECM to the actin cytoskeleton - cell binding o self association o binding to other ECM components

Two subtypes of isotonic contraction

o concentric and eccentric

What is the general structure of fibronectin?

o dimer that is joined by disulphide bond - it has various domains that can bind to different things

What is epidermolysis bullosa an example of?

o disorder of cytokeratin and desmosomes

Embryology of epidermis, dermis and melanocytes

o epidermis = ectoderm o dermis = mesoderm o melanocytes = neural crest

What is the result of a mutation in filagrin gene?

o glue between corneocytes in epidermis is not normal --> eczema

Examples of paracrine signalling

o insulin inhibits glucagon secretion by nearby alpha cells o Nitric oxide produced by endothelial cells in blood vessels causes vasodilation o Osteoclast activating factors produced by adjacent osteoblasts

Keratinisng vs non-keratinising cells

o keratinising = nuclei are not visible in the surface cells o non-keratinising = nuclei are visible in the surface cells

Describe the structure of the epidermis

o made up of keratinocytes that start out the basement membrane and differentiate and move up o separated into 4 layers

What are microtubules used for?

o movement of organelles through the cell - involves the motor proteins. o involved in spindle fibre formation

Oligodendrocyte vs astrocyte structure

o oligodendrocytes are: 1) smaller 2) denser cytoplasm and nucleus 3) absence of intermediate filaments and glycogen in the cytoplasm

What are some mechanisms to switch off intracellular signals?

o receptor inactivation o receptor down-regulation i.e. breakdown by lysosomes o the production of inhibitory proteins o inactivation of intracellular signalling protein

Summary of where the different epithelial cell types are found

o simple squamous = lung alveolar, endothelium, mesothelium o simple columnar = enterocytes o simple cuboidal = kidney collecting duct o stratified squamous = epidermis, lining of mouth, anus, cervix, vagina o pseudostratified columnar= bronchi epithelium o keratinising stratified squamous = skin o non-keratinising stratified squamous = oesophagus

Describe cell division in the villus

o there are instestinal stem cells in the mid-region of the crypt. o new cells are shunted up the villus as other new cells form o cells are lost from the tip

C protein

part of the thick myosin filament; involved in holding the tails of myosin in a correct spatial arrangement

Testosterone paradox in hair

phenomonen where in puberty pubic hair becomes thicker (vellus --> terminal) and more pigmented due to androgen. Pubic, then axillary, then beard and chest. In elderly, nose and ear hair. In scalp, similar happens in men where miniturisation occurs - each cycle, hair gets a little bit smaller, then eventually falls out as hair is wispy and unpigmented. Eventually scars and no follicle left at all. And this only happens in androgen sensitive areas. Hence androgens can cause hair growth or loss. Hair on scalp is longer due to differing anagen length. Hair on scalp is couple years, but eyelashes = couple months. Rate of growth at body sites: Vertex = 0.44mm/day Beard= 0.27mm/day

How do tight junctions establish and maintain apical-basolateral polarity?

prevent the mixing of proteins and lipids between the different plasma membrane compartments. In the fluorescence micrographs of hollow epithelial balls, it can be seen that two different proteins are confined to different regions of the plasma membrane.

Example of inhibition of epithelial proliferation

proliferation of intestinal crypt cells, e.g. in cancer chemotherapy, results in LOSS of the finger-like intestinal VILLI and FLATTENING of the intestinal mucosa. This is responsible for many of the gastro-intestinal disturbances that are side-effects of chemotherapy.

What's the difference in appearance between rer and ser except the fact that rer has ribosomes?

rERs (protein synthesis) are flattened structures whereas sERs (lipid metabolism) are more tubular.

Merkel cell

receptor cell in the stratum basale of the epidermis that responds to the sense of touch

What are gyri?

ridges of the brain

What does the sebaceous gland do?

secretes sebum

Autocrine signalling

signalling molecule acts on same cell · Activated T lymphocyte will initiate a cascade of reactions within the cell · Activated T lymphocyte expresses IL-2 receptor on surface · Activated T lymphocyte also secretes IL-2: o IL-2 can bind to the IL-2 receptor on its own surface thus having an effect on the cell o IL-2 can also bind to IL-2 receptor on adjacent activated T-cell Other examples of autocrine signalling: lots are negative feedback · Acetylcholine binds to pre-synaptic M2-muscarinic receptors · Growth factors (e.g. TGFB) from tumour cells can lead to mitogenesis in the tumour cell . When ADP is released by platelets interacted with ADP receptors on platelets and causes platelet activation and aggregation, get haemostasis and thrombosis.

Examples of striated muscle

skeletal and cardiac

What feature do real cells have which prevents them from bursting due to having a higher osmolarity inside than outside cell?

sodium-potassium pump (maintains lower conc of Na+ inside than outside)

Which collagens regulate the organising of fibrils?

some collagens e.g. IX and XII associate with collagens to regulate the organising of fibrils.

Where might see signs for nail systemic disease

sometimes will see signs at proximal nail folds • Dermoscopy - magnifying glass - see little hairpin vessels on nail cuticle, if they're disrupted can indicate systemic sclerosis. • Systemic Sclerosis (diffuse connective tissue disorder) • Giant capillaries . microhaemorrhages

Types of cells lining the oesophagus

stratified squamous epithelium. line the lumen of the oesophagus in a way which is resistant to damage. The stratified arrangement means that if the cells adjacent to the lumen become damaged, the cells underneath maintain the function of the epithelium as a barrier and can divide to replace those that are lost.

Where are melanocytes found?

stratum basale, basement membrane of epidermis

What is top layer of epidermis?

stratum corneum (looks like a basket in histology, cells have no nuclei)

Layers of the epidermis

stratum corneum, granulum, spinosum, basale Keratinocytes (make up bulk of epidermis) proliferate, move up, differentiate as move up to final destination at stratum corneum, then die As differentiate, change morphology Spinosum called that because has spinus processes which can see on light microscopy Granulosom has granules of keratin which can also be seen o Keratinocyte main cell o But also melanocytes (always sit on basement membrane), langerhan cells (APCs in epidermis) and merkel cell (sensory cell involved in sensation again near basement membrane): All of these cells can become cancerous. Keratinocyte --> squamous/basal cell carcinoma; melanocyte --> melanoma; merkel cell and langerhan also --> tumour.

Ehler's Danlos syndrome

stretchy skin, where collagen fibrils are weaker - low tensile strength.

What is oedema?

swelling of a tissue because of excess interstitial fluid.

What is the perinuclear space?

the space between the inner and outer nuclear membrane

What is signal transduction?

the transmission of an extracellular signal within a cell

What is telogen effluvium?

thinning of hair due to early entry of hair into telogen phase. Aetiologies include emotional as well as physiological stress (hypothyroidism, sepsis and anemia).

ASSERTION: In cardiac muscle cells, excitation of the sarcolemma results in a rise in intracellular calcium ions REASON: Influx of extracellular calcium ions induces calcium ion release from the sarcoplasmic reticulum.

true, true - reason is correct explanation. Note that in SKELETAL muscle release of calcium ions from the sarcoplasmic reticulum is NOT triggered by an influx of extracellular calcium ions, but instead by the voltage change in in T-tubule membrane triggering changes in DHP receptor in the T-tubule membrane and the ryanodine receptor in the adjacent SR membrane.

Crypts

tubular glands that lie between the intestinal villi, into which cells secrete substances which diffuse along the tube to their destination (secrete intestinal juices into the small intestine) If the tubes were branched the gland would be described as compound. If the secretory cells were restricted to regions with a specialised rounded shape at the ends of the tubes the gland would be described as an acinar or alveolar gland

what is the structure of actin?

two twisted alpha helices

Laminins

ubiquitous basement membrane glycoproteins. · Contains of 3 chains - one each of an a, b and g chain · Forms a CROSS-SHAPED MOLECULE · At the N terminus all the chains have Globular Regions. · Coiled-Coil Domain - where the three chains are wrapped around each other. · Very LARGE - each chain between 160 and 400 kDa · Multi-adhesive · Derived from several genes · Interact with cell surface receptors e.g. integrins and dystroglycan · Found in ALL basement membranes · Can self-associate (laminin molecules can bind to other laminin molecules) as part of the basement membrane matrix and can interact with other ECM components e.g. type IV collagen, nidogen, proteoglycans · Specific chain mutations associated with inherited disease e.g. muscular dystrophy and epidermolysis bullosa. · Largest chain is alpha chain which sticks out at end. · At self-assembly points on diagram, laminin can bind other laminins · Different regions on the laminin have different binding capacities.

What are sulci?

valleys of the brain

Examples of hyperproliferation of stratified squamous epithelium

warts caused by HPV (human papilloma virus). Repeated or constant pressure to an area of the skin can cause a callus.

What is the axon hillock?

where the axon joins the cell body (soma)

Major cell-cell junctions

zonula occludens - tight junction. apical. kiss points. more complex --> more tighter. allow polarity. block paracellular pathway. zonula adherens = adhesion belt. master junction. with actin. under tight junctions. cadherins - bind to similar molecules on adjacent cells macula adherens - desmosomes. with intermediate filaments macula communicans - gap junction.

Molecular constitution of collagens

· 28 collagen types exist in humans · There are 42 genes encoding collagens in humans. · EACH COLLAGEN MOLECULE COMPRISES OF THREE a CHAINS - FORMING A TRIPLE HELIX · Can be composed of one or more different a chains. · Type I collagen has chains from two different genes - its composition is [a1(I)]2 [a2(I)] · Types II and III collagen have only one chain type - their compositions are, therefore, [a1(II)]3 and [a1(III)]3

Intracellular receptors

· A membrane permeable ligand binds to receptor inside cell. T1 has hsp and in nucelus. T2= direct activation · Type 1 - cytoplasmic o Receptor located within the cytoplasm o Attached to chaperone molecules (heat shock proteins, hsp) o Ligands are usually STEROID hormones which pass through the membrane and act on intracellular receptors o Ligand binds to the Type 1 receptor which dissociates from the heat shock protein (so now just have receptor and ligand) o Get receptor clustering to form a DIMER. o The ligand and receptor move together to the nucleus o It binds to the DNA and causes increased or decreased TRANSCRIPTION o NOTE: the type 1 intracellular receptors perform their function as homodimers These intracellular receptors are actually transcription factors o Effects of intracellular receptors take longer to occur (hours, days, weeks) · Type 2 - nuclear o receptor located within the nucleus and is already bound to DNA o Hormone ligand comes in, moves through the nuclear envelope and binds to the receptor on the DNA causing changes in transcription EXAMPLES of intracellular receptors · Type 1 - Glucocorticoid Receptor o Ligand: cortisol, corticosterone o Physiological Effect: Downregulate immune response, increase gluconeogenesis o Agonists: Glucocorticoids · Type 2 - Thyroid Hormone Receptor o Ligand: Thyroxine (T4), Triiodothyronine (T3) o Physiological Effect: Growth & Development Agonists: Thyroid hormones

Cardiac E-C coupling

· AP in the heart muscle is generated by pacemaker cells in the nodes · The AP moves down T tubules and comes into contact with VGCCs · This causes the VGCC to open allowing Ca2+ influx DIFFERENCE: THERE IS NO CONTACT BETWEEN VGCC and RyR · The Ca2+ then binds to the RyR and causes CALCIUM INDUCED CALCIUM RELEASE (CICR) So extracellular calcium causes intracellular calcium release. · The rest of the contraction phase is the same (except there is a different kind of troponin)

Skeletal muscle function

· Attached to bone · There are antagonist muscle pairs consisting of: o Flexor (e.g. Bicep) o Extensor (e.g. Tricep) · Isotonic Contraction = muscle length changes but tension remains the same o Concentric - shortening o Eccentric - lengthening · Isometric Contraction = muscle length stays the same but tension changes Tension changes - there is a change in the tone of the muscle e.g. when you are carrying a shopping bag with your arm extended.

Regulation of tissue function by basement membranes

· BMs surround muscle, peripheral nerve and fat cells and underlie most epithelia. · BMs separate epithelial cells from connective tissue · BMs are highly specialized extracellular matrices containing distinct spectra of collagens, glycoproteins and proteoglycans. They have nothing to do with cell membranes.

Exocrine cell usual arrangement

· Basal ---> Apical direction · Granular ER and nucleus is usually in the basal part of the cell · There is a Golgi apparatus apical to the ER - it packages and processes the proteins produced. · Secretory granules are produced in the apical part of the cell and are destines for secretion. E.g. goblet cell (secretes mucus) or pancreatic acinar cell (secretes digestive enzymes)

Basement membrane aka basal laminae - what is it?

· Basal lamina is a special type of ECM. . They are flexible, thin mats of ECM underlying epithelial sheets and tubes. Made of type IV collagen and laminins

Prenatal Diagnosis of Osteogenesis Imperfecta

· Biopsy is impractical and risky on a foetus · Chorionic Villus Sampling (CVS) - screen the foetal DNA obtained · Amniocentesis which is amplified by PCR can also be used SPECIFIC probes must be designed which bind with the part of the DNA sequence where a mutation was KNOWN to occur.

Different ways of secreting materials?

· CONSTITUITIVE - secretory vesicles, as they are formed, move directly to the plasma membrane and release their contents e.g. production of plasma proteins by hepatocytes (constituitive endocrine secretion) · STIMULATED - secretory vesicles are stored in the cytoplasm and only fuse with the plasma membrane to release their contents when stimulated. E.g. the release of adrenaline from cells of the adrenal medulla after a fight-or-flight stimulus (stimulated endocrine secretion); when stomach contents enter the duodenum, pancreatic acinar cells are stimulated to release their digestive enzymes into ducts (stimulated exocrine secretion)

What causes congenital muscular dystrophy?

· Caused by Absence of a2 in laminin 2

Congenital muscular dystrophy

· Caused by Absence of a2 in laminin 2 · Has laminin beta 1 and gamma 1 but not alpha 2 · Symptoms evident from birth · Hypotonia (abnormally low muscle tension) · Generalised weakness Deformities of the joints

Cell-cell junctions

· Cell-cell adhesions that can form intercellular junctions are key for the formation and maintenance of epithelia. continuous epithelial layers can form because cells make stable cell-cell junctions which give the epithelia mechanical integrity and act to seal the intercellular pathways of the layer · Continuous epithelial layers can form because cells make stable cell-cell junctions. · The cell-cell junctions are found in the apical region of cell-cell contact as a junctional complex. · Two Forms of Cell-Cell Junction: Zonulae (belts) and Maculae (spots) · Arrangement of Junction in epithelia: Apical ---> Basal o Tight Junction o Adhesion Belt o Desmosomes and Gap Junctions . Gap Junctions - main function isn't to hold the cells together or to seal the spaces between the cells but actually to communicate between the cells.

Important points about cell-cell junctions

· Cell-cell junctions are capable of changing their assembly and organisation. . The dynamic assembly and disassembly of junctions are controlled by a variety of factors in health and disease.

Osteoarthiritis

· Characterised by excessive loss of extracellular matrix (erosive disease), esp. in joints · The cushioning properties of cartilage over the end of long bones are lost affects people mainly over 65 · This can lead to joint stiffness and the rubbing of bone against bone. · Strong genetic component but genetics complex · Can affect any joint but often affects fingers and knees · What happens: o The cartilage is there to cushion compression in joints o There is a loss of cartilage, inflammation and new bone formation o Can see swelling of joints in pictures. · With age: cleavage of aggrecan by aggrecanase and metalloproteinase. Loss of aggrecan fragments get lost to the synovial fluid. Can no longer form aggrecan aggregates

Elastic fibres - function and components

· Collagen good for tensile strength and elastic fibres important for the elasticity of tissues. · Important for the elasticity of skin, blood vessels and lungs. · Often, collagen and elastic fibres are interwoven to limit the extent of stretching. · Elastic Fibres = Elastin Core + Microfibrils In elastin core: elastin and microfibrils (rich in the protein FIBRILLIN)

Normal pressures in a capillary?

· Colloid Osmotic Pressure (COP) - Osmotic Pressure due to plasma protein (more protein inside vessel than outside). COP draws water in · Hydrostatic pressure is pressure in a circulatory system exerted by the volume of blood when it is confined in a blood vessel. Hydrostatic pressure pushes water out · Solute and fluid movement across a vessel wall is determined by the balance between the opposing pressures. o Hydrostatic Pressure > COP = Plasma Leaks Out Hydrostatic Pressure < COP = Flow Into Vessel

Main cell types

· Connective (mesenchymal) tissue cells: fibroblasts (many tissues), chondrocytes (cartilage), osteocytes (bone). · Contractile tissues: skeletal muscle, cardiac muscle, smooth muscle. · Epithelial Cells - cells forming continuous layers - the layers line surfaces and separate tissue compartments. · Haematopoietic Cells - blood cells and cells of the bone marrow from which they are derived ·Neural Cells - nervous system - 2 main types: neurones (carry electrical signals) and glial cells (support cells)

Connective tissue

· Connective tissue is rich in extracellular matrix · Basal Lamina - separates epithelial cells from the underlying connective tissue · Macrophages are present in connective tissue Connective Tissue = Extracellular Matrix + Component Cells (e.g. macrophages)

ECM

· Definition - material deposited by cells which forms the insoluble material that you will find extracellularly (e.g collagen, elastin, proteoglycan) · ECM molecules tend to be formed of fibrillar proteins and form fibres. · These fibres can form networks (described as reticular). · They are often embedded in large ECM molecules which are very hydrated and form gel like structures like proteoglycans or "ground substance". They often have no apparent organisation (appears random) or they appear very organised (tendons and bone).

e-c coupling in smooth muscle

· Depolarisation activates and open the VGCC (slightly different from the VGCC in cardiomyocytes) causing Ca2+ influx · The calcium moves into the cell and binds to Calmodulin (CaM) forming a Ca2+-CaM complex · Ca2+-CaM complex activates Myosin Light Chain Kinase (MLCK) · MLCK phosphorylates myosin light chains (MLC20) · Cross-bridges with actin filaments --> contraction · This changes the appearance of smooth muscle cells from elongated to contracted This leads to vasoconstriction

What happens when the glomerulus becomes diseased?

· Diabetic Nephropathy - glomerulus looks different. Basement membrane much thicker ECM accumulation - Impinging on capillaries - restricts renal filtration - RENAL FAILURE. . Alport syndrome: Due to mutations in code for collagen IV Progressive loss of kidney function and hearing loss BM is abnormally split, filtration ears, and kidney loss function

Alignment of collagen fibrils

· Different layers of collagen fibrils are laid down nearly parallel to each other · This gives the tissue TENSILE STRENGTH - the ability to resist stress and not snap. · This can resist tensile force in two directions. · Skin - successive layers are at right angles to each other. · Same arrangement in mature bone and in the cornea. · This gives the tissue the ability to resist tensile force in all directions. IMPORTANT CONCEPT - The alignment of the collagen fibrils determines which directions the tissue can resist tensile force in.

Summary of ECM Part 1

· ECM is a feature of all multicellular organisms. · ECM provides mechanical stability and influences the behaviour of cells in contact with the ECM. · Major components of the ECM: Collagens + Multi-adhesive Glycoproteins + Proteoglycans · Collagens - major fibrillar proteins and provide tensile strength. · Elastic Fibres - important for the elasticity of tissues. · Basement Membranes (basal laminae) - glycoprotein networks closely associated with cells. Major constituents of Basement Membranes: Collagen IV + Laminins

composition of elastic fibres

· Elastic Fibres = Elastin Core + Microfibrils In elastin core: elastin and microfibrils (rich in the protein FIBRILLIN)

Methods of transport across a membrane

· Endocytosis and Exocytosis o Encapsulation in membrane as solute enters or before it leaves the cell. o Generally large molecules o E.g. endocytosis of nerve growth factors (proteins), exocytosis of peptide hormones from endocrine glands · Passive - Down an Electrochemical Gradient o Through Lipid o Through Pores o On Carriers · Active - Against an Electrochemical Gradient o On Carriers - primary active transport - e.g. Na+/K+ Pump On Carriers - secondary active transport - uses downhill movement of one solute coupled to uphill movement of another solute (i.e. exploiting the potential energy of Na+ - glucose symport)

Tumours retain characteristics of cell type they originate from

· Epithelial Cancers = Carcinoma · Mesenchymal Cancers (connective tissue and muscle)= Sarcomas · Haematopoietic Cancers = Leukaemias (bone marrow cells) + Lymphomas (lymphocytes) Neural Cancers = Neuroblastomas (neurones) + Gliomas (glial cells)

Ependymal cells

· Epithelial Cells of the CNS o Line fluid filled ventricles - full of cerebrospinal fluid · Regulate production and movement of cerebrospinal fluid (CSF)

epithelial polarity

· Epithelial functions require polarity. Most epithelial functions must be directional e.g. secretion, fluid and solute transport, absorption etc. · Need epithelial polarity to give directionality to epithelial function i.e. one surface of epithelium is different from the other · Plasma membrane polarity is key to epithelial polarity · Junctions separate many epithelial membranes into two biochemically and functionally distinct domains (apical and basolateral domain) --> for polarity · These two domains have different lipid and protein composition, and have distinct functions · Cells have an apical, basal and lateral surface. · epithelial layers have a distinct polarity, with an apical surface at the lumenal (open) surface, and a basal surface in contact with the extracellular matrix · the membrane between these two surfaces, where adjacent membranes oppose each other, is the lateral membrane Basal and Lateral surfaces are grouped together and is called the basolateral domain.

Epithelium General Characteristics

· Epithelial organs have associated ECM and connective tissue cells. · Layer of epithelia lies on the basal lamina. · Under the lamina you have interstitial connective tissue and extracellular matrix. · Epithelial cells make organised, stable cell-cell junctions to form continuous cohesive layers. In many epithelia, junctions are found at the apical region of cell-cell contact as a junctional complex. · Epithelial layers line internal and external body surfaces and have variety of functions e.g. transport, absorption, secretion, protection cell-cell junctions are key to the formation and maintenance of epithelial layers

Examples of ionotropic receptors

· Example 1: Nicotinic Acetylcholine Receptor o Location: skeletal muscle at neuromuscular junctions - it begins the depolarisation which leads to muscle contraction. o Ligand = acetylcholine. o Physiological effect: muscle contraction · Nicotinic Acetylcholine Receptors can be found in the brain as well. · Example 2: GABAA o Location: many cells in the CNS o Ligand: gamma-amino butyric acid (GABA) o Physiological effect: · Allows transmission of anions · GABA binds to the receptor and causes the opening of the pore which allows an influx of chloride ions · GABA acting on cells will cause a depression of activity If you block the GABA receptor you get hyperexcitability of the CNS and possibly epileptic seizures

Resting Membrane Potential (RMP)

· FOUR MAJOR PHYSIOLOGICAL IONS: o Na+ o K+ o Ca2+ o Cl- · Cell membranes are impermeable to these ions - transport is regulated by pumps and channels · This causes uneven distribution of ions: o High Extracellular - Na+ and Cl- o Low Extracellular - K+ o High concentration gradient into the cell of Ca2+ because of very low concentrations inside the cell. · The differences in concentration creates a potential difference across the membrane · Neuronal Cells: o Negative Charge Inside COMPARED TO INSIDE o Resting Membrane Potential = -40 to -90mV. As comes closer to 0 = deplorisation, opposite is hyperpolarisation. When cell is closer to -90 is less excitable as needs more change o Positive and negative charges are concentrated around the membrane · Normal Values: Ion K+ Na+ Ca2+ Cl- Concout 4 140 2 120 Concins 150 10 0.0001 5 N.B. conc outside and inside is in mM. NEED TO KNOW THESE VALUES

Fibronectins

· Family of closely related glycoproteins of ECM and body fluids · NOT found in basal membranes but is a major connective tissue glycoprotein. · Can exist as insoluble fibrillar matrix OR soluble plasma protein · Only derived from ONE GENE - different forms of fibronectin come from alternate mRNA splicing at RNA level. · Multi-adhesive · LARGE multidomain molecule. Form dimers around 500kDa in size. Capable of interacting with cell surface receptors and other matrix molecules. · Important in regulating cell adhesion and migration in embryogenesis and tissue repair · Important for wound healing (promotes blood clotting) · NO KNOWN MUTATIONS IN HUMANS - suggests that it is essential for life · Forms a mechanical continuum with the actin cytoskeleton of many cell types · V shaped molecules . · Dimer · Two chain units are linked by a disulphide bridge · There are different regions within the molecule that are responsible for interacting with different components. · Fibronectin is linked to the actin cytoskeleton via integrins Fibronectin ---- Integrin ---- Actin · The extracellular region of the integrin links with fibronectin and the intracellular region links with actin. · Integrin receptors at the cell surface provide linkage between matrix and cytoskeleton · They are called 'integrins' because they integrate the intracellular area with the extracellular area. · Integrin binds to fibronectin via RGD molecules · · Integrin binds to the RGD sequence (Asp, Gly, Arg) which is on the cell binding site. · Integrins recognise the RGD motif

Adhesion belt (zonula adherens)

· Formed just basal to the apical tight junction. · transmembrane adhesion molecule is a cadherin (family of Ca2+-dependent cell adhesion molecules) · Cadherins - bind to similar molecules on the adjacent cell and cluster (with the help of actin) to form these junctions. · this junction controls the assembly of the other junctions ("master junction") · The actin cytoskeleton is closely associated with these junctions. · When epithelial cells touch one another, the adherens junction is the first to form. After the adherens junction has formed, other junctions can begin to form - hence it is the Master Junction.

Synapses

· Found in neural tissue and where nerves contact other tissues · Button- like junctions formed between neurones or their targets · Pass information in one direction via a chemical signalling system · a variety of chemical signals and receptors are utilised at synapses

Lysine and proline hydroxylation in collagen

· Hydroxyl group is important because it contributes to interchain hydrogen bond formation. · Lysine and hydroxylysine are also modified in the formation of covalent cross-linkages. This takes place after the collagen is secreted. · Hydroxylation is carried out by Prolyl and Lysyl Hydroxylases. · Prolyl and lysyl Hydroxylases require VITAMIN C and IRON ion (Fe2+) to function. · Lack of Vitamin C - lack of proper collagen hydroxylation which can't aggregate together properly to form solid fibres - affects tissue stability (scurvy). · VITAMIN C AND IRON ION IS NEEDED FOR HYDROXYLATION of proline and lysine. Covalent cross-links: · Provides tensile strength and stability · Lysine and hydroxy-lysine residues are involved · The type and extent of cross-links in tissue changes with age. Achilles tendon has lost of cross-links to give more tensile strength

Microglial cells?

· Immune cells of the CNS · Similar to macrophages NOTE: Not to be mistaken with 'neuroglia'. Neuroglia = all cell types within the CNS except neuronal cells.

Barriers to fluids in tissues

· In most tissues, extracellular environment is compartmentalised. Different compartments have different compositions and functions · Extracellular fluids are compartmentalised by barriers: · Barrier = plasma membrane, separates intracellular and extracellular fluids · Extracellular fluids (apical, basal (interstitial), plasma) are separated by layers of cells that form junctions with each other: o Epithelial cell layers on top of basal lamina separate various interstitial spaces Endothelial cells line blood vessels, and are the main barrier separating the fluid of the blood (plasma) and the interstitial fluids

What is the need for tissue preservation in transplantation?

· In transplantation, transportation of donated organs and tissues often required · When any tissue loses its blood supply, ischaemic changes occur, but these can be significantly slowed by rapid cooling of the tissue/organ to 0 - +4°C. · Tissues are perfused with cold solutions via the arterial supply. · Even when cooled, tissues/organs deteriorate. BUT, The composition of the perfusion solution can reduce the deterioration in hypothermia, prolonging the time available to transport and keep viable. · After cooling, sodium pumps in cells stop working below 15°C. (also no O2 or ATP to fuel the pump) · Hence, Na+ will enter the cell (with Cl-) and water will also enter, K+ exits. Cells will swell and bleb which can cause cell death.

Assembly of collagen into fibres

· Individual triple helices come together to form FIBRILS . Fibrils come together to form COLLAGEN FIBRES

Marfan's syndrome and Fibrillin-1

· Integrity of elastic fibres depends on microfibrils containing the protein fibrillin. · Marfan's Syndrome - mutation in FIBRILLIN-1 · Manifestations primarily involve the skeletal, ocular and cardiovascular systems. · People with Marfan's Syndrome tend to have an arm-span which is longer than their height. · Predisposed to aortic ruptures.

Summary of ECM 2

· Laminins and Fibronectin are multi-adhesive glycoproteins that can interact with other matrix components and cell surface receptors - thus attaching cells to the matrix. · Proteoglycans consist of a core protein, which is covalently linked to one or more glycosaminoglycan (GAG) chains. · GAG chains form hydrated gels, which resist compression. · A major cartilage matrix component is aggrecan, which forms huge aggregates with hyaluronan. · Osteoarthritis is an erosive disease, where excessive ECM degradation results in destruction of cartilage. Fibrotic disorders are characterised by excessive production of fibrous connective tissue.

G-protein coupled receptor

· Ligand binding --> activates intracellular G-protein · G-protein exists as a heterotrimeric complex o Trimer = alpha, beta and gamma subunits (GDP is NOT part of the heterotrimer) o Beta and Gamma do NOT dissociate (always bound together as one unit) · G-protein coupled receptors aka serpentine receptors and 7-TM receptors (crosses the membrane 7 times - '7 transmembrane') · 7-TM has extracellular ligand-binding N terminus and intracellular G-protein binding C-terminus · Heterotrimer isn't attached to the G-protein receptor to begin with (in resting state); 7-TM receptor and heterotrimeric G-protein are inactive · Signal Transduction Events: o Ligand binds and changes conformation of the receptor and is now available for binding o G-protein heterotrimer binds to the internal compartment of the G-protein coupled receptor (so have ligand bound on outside of cell and G-protein inside cell all via the 7-TM receptor) o GDP is exchanged for GTP molecule o GTP provides energy for the G-protein to dissociate two active components: 1) alpha subunit 2) beta-gamma subunit o The subunits go and bind to their target proteins o Once the alpha subunit has attached to the target protein, internal GTPase activity within the alpha subunit causes the GTP molecule to change to a GDP molecule o This allows the alpha subunit to unbind from the target protein and reform the heterotrimer with GDP attached · NOTE: all this time the ligand has been bound to the receptor - many G-protein heterotrimers can be activated so long as the ligand is bound to the receptor.

coated vesicle formation

· Ligands binds to the receptors and become internalised - receptor mediated endocytosis · Once internalised, the ligands are released. NOTE: this is the way we get iron into the cell. Iron binds to transferrin and transferrin binds to receptors, which are internalised then the iron and transferrin become unbound.

Desmosome (macula adherens)

· Macula Adherens - SPOT junction · They are dotted between adjacent cell membranes · transmembrane cell adhesion molecule is a cadherin-like molecule · Desmosomal Cadherins link to the intermediate filament cytoskeleton (cytokeratin in epithelium). · provides good mechanical continuity between cells · Very abundant in the epidermis · Intermediate filaments don't pass between the cells, they stop at the junctions.

Gap junction (macula communicans)

· Made up of clusters of pores, formed from 6 identical subunits in the membrane - these pores are continuous with pores in adjacent cell membrane. · Allow the passage of ions and small molecules between cells. · They can open and close the pores (control intercellular communication) - can be controlled by:pH, (voltage) electrical activity, calcium concentration · They are clusters of integral membrane proteins which associate with identical ones on the opposite membrane. · Only relatively small molecules and ions can get through. · also known as the electrical synapse; important in the passage of electrical signals in some tissues

Enzyme-linked receptor

· May also be referred to as tyrosine kinase receptors (as 98% of enzyme-linked receptors) · In diagram shows 2 receptors, but can have 3,4,5 etc. · Ligand binding --> receptor clustering --> activates internal enzymes · Ligand binds and the receptors cluster · Receptor clustering activates enzymes in the intracellular compartment · Enzymes and proteins are attracted to the receptor and move towards it to become activated · Activated enzymes phosphorylate receptor ---> leads to binding of signalling proteins to the cytoplasmic domain · Signalling proteins recruit other signalling proteins and a signal is generated within the cell · NOTE: The vast majority of these receptors are linked to TYROSINE KINASE ENZYMES · Tyrosine kinase phosphorylates any protein which has a tyrosine amino acid within it (a large proportion of the proteins within the cell) · The signal is terminated when a phosphatase removes the phosphate group from receptor · Examples in RHS diagram above are important in cell growth and proliferation - so now many drugs target tyrosine kinase receptors i.e. in cancer medication · EXAMPLES: o Insulin Receptor (CD220 antigen) · Ligand: Insulin · Physiological effect: glucose uptake and reduce glucagon secretion from alpha cells o ErbB Receptor · Big family of receptors · Ligand: Epidermal Growth Factor, Transforming Growth Factor b · Physiological effect: cell growth, proliferation Other types of enzyme-linked receptors: · Guanylyl-cyclase linked receptor o EXAMPLE: NPRA · Ligand: Atrial/Brain natriuretic peptide · Physiological effect: Vasodilation, decrease in blood pressure · Ser/Thr kinase linked receptor o EXAMPLE: TbR1 · Ligand: Transforming Growth Factor b Physiological effect: apoptosis

Hyaline cartilage

· Most abundant type of cartilage · Found in nose, larynx, trachea, bronchi, ventral ends of ribs and articular ends of long bonds · Rich in AGGRECAN proteoglycan · Cushions the ends of long bones Aggrecan is responsible for this cushioning effect

Oligodendrocytes

· Myelin is generated by GLIAL CELLS and extends spirals of membrane around the axons of many neurons. · CNS - myelin is formed by oligodendrocytes · Variable morphology and function · Numerous projections that form internodes of myelin · Differences between oligodendrocytes and astrocytes: o Oligodendrocytes are smaller o Oligodendrocytes have a denser cytoplasm and nucleus o Absence of intermediate filaments and glycogen in the cytoplasm · ONE OLIGODENDROCYTE MYELINATES MANY AXONS

NaCl osmolarity vs conc?

· NaCl dissociates into Na+ and Cl- so there is double the number of solute particles as the number of NaCl introduced to the solution hence osmolarity is double the concentration. Glucose does NOT disassociate

Models of basement membrane

· On top of plasma membrane have sheet-like network of basement membrane, which is ECM and have key components of basement membrane. Collagen IV present in all BMs, also laminin (also forms 2D networks), also perlecan and nidogen · There is a network of interacting matrix molecules. · Integrin - cellular receptor, binds to laminin KEY COMPONENTS: Type IV collagen and laminin

GAG (glycosaminoglycan) chains

· One of the two sugars in the repeating disaccharide is always an amino sugar. · Highly Negatively Charged - many GAGs are sulfated or carboxylated · Small proteoglycans have one GAG chain where as large ones can carry around 100 GAG chains. GAG chains and the core protein of a proteoglycan are linked via a LINK TETRASACCHARIDE · Four main groups of GAG chains: o Hyaluron o Chondroitin Sulfate/Dermatan Sulfate o Heparan Sulfate o Keratan Sulfate

Function of ECM

· Physical Support · Determines the mechanical and physicochemical properties of the tissue · Influences the growth, adhesion and differentiation status of the cells with which it interacts. · Essential for development - tissue function and organogenesis NOTE: Cell = Bricks, ECM = Mortar NOTE: Molecules in the ECM can interact with receptors on cells. This interaction will influence the behaviour of cells. ECM in a simple organism - Extracellular matrix is an essential component of all metazoans e.g. hydra vulgaris. It is as ancient as multicellular life itself. You need extracellular matrix for the existence of MULTICELLULAR LIFE. · Hydra is made of two layers of cells with extracellular matrix in the middle. · YOU NEED ECM FOR MULTICELLULAR LIFE

Composition of main fluid compartments

· Plasma is an example of extracellular Fluid - it is very similar to interstitial fluid except plasma has MORE protein. · The fluid in muscle is an example of intracellular fluid. · CATIONS: o Sodium is present in high concentrations outside cells (main extracellular) o Potassium is present in high concentrations inside cells(main intracellular) o Free Calcium(Ca2+) is an important signalling ion - it is present in very low concentrations inside cells though there are some compartments which store calcium (e.g. ER) · Other intracellular cations (e.g. Mg2+) are present in significant amounts · ANIONS: o Chloride is present in high concentrations outside cells(main extracellular) o Organic Phosphates are present in high concentrations inside cells(main intracellular) o PROTEINS are also anions, which are present in LOW concentration but have a HIGH CHARGE. (protein conc in interstitial fluids is around 0.1-0.4mmol/l). Protein is higher in intracellular > extracellular · pH: o pH is slightly higher outside the cell than inside o Hence, there is a lower [H+] outside cells o Note - pH scale is log scale, so difference between 7.1 and 7.4 is actually that 7.1 has double amount of H+ · EC osmolarity=IC osmolarity (exception is some parts of kidney) Overall: Na+ is main EC cation // K+ is main IC cation Ca2+low IC conc. --> allows for big change in conc. Cli- is main EC anion // Organic phosphates are main IC anion

Microtubules

· Polymers of a and b tubulin ~20nm in diameter MTs often radiate from a central structure in cell (MTOC) - microtubule organising centre Involved in cell shape and act as tracks for the movement of organelles and cytoplasmic components within the cell. Many accessory proteins required for this. · Motor proteins are necessary for this movement. · It is a major component of cilia and flagella. · Microtubules are part of the spindle fibres involved in mitosis. · Microtubules are the major structural component of cilia and flagellae.

Microfilaments

· Polymers of globular protein actin associate with adhesion belts in epithelia and endothelia and with other plasma membrane proteins. · 5-9nm diameter · Involved in cell shape and cell movement (crawling and contractility esp. muscle) · Accessory proteins which associate with actin e.g. myosin · Monomer = Globular Actin (G-actin) · Microfilaments = Filamentous Actin (F-actin) · Usually bundled near the (cortical) periphery of the cell. · Has a helical structure · As well as being part of contractile apparatus of muscle, but also in contraction of non-muscle cells Actin more in outside (periphery of cell) and microtubules on inside

Smooth muscle

· Present within walls of all hollow organs (e.g. blood vessels, gastrointestinal tract). · Do NOT contain regular arrangement of actin & myosin · Smooth muscle will multiply and get bigger without going to the gym - it doesn't need as much attention as cardiac and skeletal muscle · Smooth - because you DO NOT get the striated pattern of actin and myosin that you get in skeletal and cardiac muscle - though it does still contain actin and myosin · CONTRACTION IS DIFFERENT IN SMOOTH MUSCLE · Smooth muscle contracts more slowly and ec coupling is different: · Depolarisation activates and open the VGCC (slightly different from the VGCC in cardiomyocytes) causing Ca2+ influx · The calcium moves into the cell and binds to Calmodulin (CaM) forming a Ca2+-CaM complex · Ca2+-CaM complex activates Myosin Light Chain Kinase (MLCK) · MLCK phosphorylates myosin light chains (MLC20) · Cross-bridges with actin filaments --> contraction · This changes the appearance of smooth muscle cells from elongated to contracted This leads to vasoconstriction

Usual arrangement for an endocrine cell

· Pretty much the reverse of the arrangement for exocrine secretion - apparatus is orientated in the opposite direction · Secretory granules are basal · Nucleus and ER are on the apical side Golgi Apparatus is in between

Schwann cell

· Produces myelin for peripheral nerves ONE SCHWANN CELL MYELINATES ONE AXON SEGMENT

Simple columnar epithelium

· SIMPLE = One cell layer thick · COLUMNAR = taller than they are wide · This is SIMPLE COLUMNAR EPITHELIUM · E.g. enterocytes (intestinal absorptive) and many other absorptive and secretory epithelia

Simple cuboidal epithelium

· SIMPLE = One cell layer thick · CUBOIDAL = as wide as it is tall · This is SIMPLE CUBOIDAL EPITHELIUM E.g. lining kidney connecting duct and many other ducts

simple squamous epithelium

· SQUAMOUS = FLAT (wider than they are tall) · It is only a single layer so it is SIMPLE · This is SIMPLE SQUAMOUS EPITHELIUM · NOTE: Squamous = Plate Shaped · E.g. lung alveolar (air sac) - thin for gas exchange, mesothelium, endothelium lining blood vessels

Decorin

· Small proteoglycan . Single GAG attached . Dermatan sulfate chain · Binds to collagen fibres - helps regulate size and arrangement of collagen fibers · Essential for fiber formation · Mice who cannot make decorin have fragile skin and reduced tensile strength · Regulates collagen fibre size and arrangement

Action potential

· Sodium and potassium ions play important role · There is normally high sodium outside and high potassium inside. · At RMP: VGSCs (voltage gated sodium channels) and VGKCs (potassium) are closed. 1) When membrane potential changes from -70mV to around -40mV due to stimulus (e.g. photon of light) the VGSC opens leading to influx of Na+. This causes a rise in membrane potential (further depolarisation) 2) Then the VGKC opens at a slower rate (hence action occurs after sodium channel, nothing to do with position) and you get efflux of K+ --> membrane repolarisation AP leaves Na+ & K+ imbalance ® need to be restored · Na+-K+-ATPase (pump) restores the ion gradients 1) Resting configuration - Na+ enters vestibule & upon phosphorylation the ions are transported through protein 2) Active configuration - Na+ removed from cell and K+ enters the vestibule 3) Pump returns to resting configuration: K+ is transported back into the cell (3Na out per 2 K in). 80% of ATP from body used in Na-K pumps Hyperpolarisation - more negative. Repolarisation - more negative back from depolarisation

How does exchange between extracellular and intracellular compartments occur?

· Solutes and water move across cell membranes and can change cell volume · Diffusion (spontaneous movement of solute) down conc grad till reach diffusion equilibrium · Osmosis: movement of water down its own concentration gradient. Moves water toward area of higher osmolarity & can change cell volume

Golgi apparatus structure

· Stacked, membrane bound, flattened sacs involved in modifying, sorting, and packaging macromolecules for secretion/ for delivery to other organelles. · Vesicles carry macromolecules from the Golgi apparatus to various destinations. · Cis faces ER, trans faces away The nuclear envelope, ER, and Golgi apparatus are a continuum of dynamic intracellular membranes that exchange membrane vesicles with each other, and with the plasma membrane. These processes are key for cellular function.

Aggrecan and cartilage function

· The GAGs (e.g. chrondoitin sulfate) of aggrecan are highly sulfated and there are many carboxyl groups - this makes it HIGHLY NEGATIVELY CHARGED · The high negative charge attracts cations that are osmotically active (e.g. Sodium) · So a large amount of WATER is retained by this highly negatively charged environment · It forms a gel - if you put pressure on the structure, the water gets squeezed out and if the compressive load is removed - the water returns. This is how aggrecan in cartilage matrix can withstand compressive forces.

Villi

· The intestinal epithelium is simple columnar with absorptive and secretory cells. · Darker cells are the enterocytes (absorptive) and the cells with pale apical cytoplasm are Goblet cells (secrete mucus). The projections down into the wall of the epithelium (labelled C) are crypts - they are tubular glands.

Parts of nucleus

· The nuclear envelope is a double membrane. · Nucleolus - site of production of subunits of ribosome. Most distinct sub-nuclear structure. Has clusters of rRNA genes that are present at the ends of different pairs of chromosomes (5 pairs in humans: ~300 copies of the rRNA genes). The nucleolus also contains the synthesised rRNA and proteins being assembled to make the ribosome subunits. We need so many rRNA genes because 1 rRNA per ribosome, unlike RNA where one can code for a protein many times. · The subunits are made of ribosomal RNA and associated proteins · The nuclear envelope is continuous with the ER which is involved in packaging and processing proteins. · Nuclear pores are complexes, they are not just holes in the membrane. Control import and export of macromolecules into and out of nucleus The nuclear lamina is a specialised type of cytoskeleton formed on the internal surface of the nuclear envelope. Important in controlling the assembly/disassembly of the nuclear envelope in cell division.

Absorptive and transporting epithelia

· The proximal convoluted tubule absorbs glucose and water. · The distal convoluted tubule pumps ion and water and controls the volume of the urine. · The ion pumping cells have mitchondria which run parallel between the apical and basal membranes. · TEM shows the junction of the proximal convoluted tubule (PT) and the thin limb of the loop of Henle (TL). Adjacent, the walls of segments of distal convoluted tubules (DT) can be seen. In this one image, three different functional epithelia can be seen: an absorptive epithelium (PT), a fluid transporting epithelium (DT) and a selectively permeable epithelium (TL):

Why do normal cells in body NOT burst when there is higher concentration of impermeable solutes inside cells?

· Their membranes are permeable to water and the concentration of impermeable solutes (proteins) is higher inside cells than outside the cell in interstitial fluid but they DO NOT BURST · This is because the SODIUM-POTASSIUM PUMP maintains a lower concentration of sodium inside the cell than outside. · The pump, in some sense, makes the membrane impermeable to sodium ions because any sodium ions, which diffuse in are pumped back out. · There is no net movement of sodium ions across the membrane. · The intracellular osmolarity of impermeant solutes (mainly high concentration of proteins and low concentration of Na+) balances the extracellular osmolarity of impermeant solutes (mainly high concentration of Na+). · Cells must actively maintain this state.

Pseudostratified columnar epithelium

· There appear to be two layers of cells in the micrograph. On further investigation, they found that all the cells are in contact with the basal lamina hence only one layer . e.g. upper airway (bronchi and trachea) epithelium

Exchange across the capillary wall

· There are small PORES between endothelial cells. · 8L of plasma leaks out of the blood vessels every day. The volume of blood is 3L so the entire plasma volume must pass into the interstitial space and return to the blood circulation every 9 hours. Lipid-soluble and small water-soluble passes readily. Plasma proteins can't really. Exchangeable proteins are moved across by vesicular transport.

Endoplasmic reticulum structure

· There is a physical continuity between nuclear envelope and endoplasmic reticulum. The flattened sacs of membrane of the endoplasmic reticulum (and of Golgi apparatus) are known as cisternae (singular- cisterna). · rER (granular)- exists as flattened sheets which is studded on its outer surface with ribosomes. · sER (agranular)- more tubular and lacks ribosomes. Involved in detoxification and lipid metabolism. The enzymes involved are typically associated with the membranes. SER is also the site of Ca2+-storage in cells (which is important in many cell-signalling contexts).

Sliding filament theory

· Troponin is attached to tropomyosin. Troponin forms a helix around the actin filament - troponin is what the Ca2+ actually binds to · Troponin causes tropomyosin to move exposing charged myosin head · Charged Myosin Head = with ADP bound. Binds to actin filament; discharge of ADP causes power stroke pulling actin to centre of sarcomere ATP attaches to myosin head which causes myosin head to release from actin chain; ATP is hydrolysed to ADP, which provides energy to 'recharge' the myosin head.

How does epithelium increase SA for efficient absorption?

· Tubular tissues make tube longer to increase SA of lining · Or can fold the lining to form structures like villi in the small intestine · Increase the SA of the apical membrane by creating tubuluar protrusions (microvilli)

Examples of intracellular receptors

· Type 1 (cytoplasmic) - Glucocorticoid Receptor o Ligand: cortisol, corticosterone o Physiological Effect: Downregulate immune response, increase gluconeogenesis o Agonists: Glucocorticoids · Type 2 (nuclear)- Thyroid Hormone Receptor o Ligand: Thyroxine (T4), Triiodothyronine (T3) o Physiological Effect: Growth & Development Agonists: Thyroid hormones

Protective epithelia

· Type of epithelia involved in protection is usually STRATIFIED SQUAMOUS EPITHELIA (both keratinizing and non-keratinizing) e.g. skin epidermis, lining of the oesophagus. · Two forms of stratified squamous epithelia: o Keratinizing - where the cells of the upper (surface) layers are "dry", because the cells have hardened and died; their nuclei are not visible e.g. dry surface of skin Non-Keratinizing - the upper (surface) layer is "wet", because the cells are alive; their nuclei are visible. E.g. oesophagus · Can form thick layers that protect underlying tissues from various chemical and physical damage e.g. heat, cold, solvents (alcohol), abrasion etc. = A BARRIER · The skin consists of three main layers: epidermis, dermis and hypodermis · The epidermis is the keratinizing stratified squamous epithelial layer. · However, some epidermal appendages have other functions (e.g. hair, nails). · The cells in the skin go through a programme of differentiation as they move up towards the surface. When subject to mechanical irritation the stem cells are stimulated to proliferate to replace the lost cells.

Osteogenesis imperfecta

· Typical Feature - repeated fracture of long bones, can be misdiagnosed as child abuse · Cause: POINT MUTATION in the gene for TYPE I COLLAGEN where G ----> T (GGC --> TGC) · This results in SUBSTITUTION OF GLYCINE WITH CYSTEINE · The larger amino acid causes a kink in the normally straight triple helix - this affects the assembly into fibres. · Cysteine has a reactive SULPHYDRYL GROUP in it's side chain so, not only is the formation of the triple helix disrupted, but there can be inappropriate disulphide bonds between the two a1 chains in the helix. · The resulting cross-linked polypeptides will migrate more slowly than the individual chains when examined by electrophoresis in the presence of SDS (sodium dodecyl sulphate - the speed of migration of proteins on electrophoresis depends on their size and NOT their charge). · 2-mercaptoethanol - reduces the disulphide bonds between cysteine residues in proteins e.g. -S-S- ---> 2 -S-H · In the presence of 2-mercaptoethanol, the disulphide bonds will be cleaved allowing the chains to migrate across the gel according to their molecular mass, which isn't that different to the molecular mass of the normal chains. In the electrophoresis, two a1 chain bands may appear if the patient is heterozygous for the mutation. Consequences of deformed collagen · The major consequence is in the formation of bone. · Bone is formed by laying down HYDROXYAPATITE (a form of calcium phosphate) on an ordered scaffold of collagen-I. The abnormal collagen leads to defects in the mineralisation process, so the patient ends up with skeletal abnormalities and generally weak bones.

Absorptive epithelium

· Villi formed from folding of small intestine wall. Villi are covered with intestinal epithelial cells · More SA --> more SA of epithelium lining for absorption --> efficient · SB = Striated Border = brush border - made up of microvilli Carriers transporting nutrients are found on the microvillous brush-border membranes, e.g. absorptive intestinal cells (enterocytes); kidney proximal tubule cells.

Neuromuscular junction signalling

· Voltage-gates sodium channel (VGSC) opens - membrane depolarisation · VGKC opens - membrane repolarisation · Calcium influx through VGCC - leads to vesicle exocytosis · Acetylcholine (ACh) binds to sarcolemmal nicotinic receptors (nAChR) · ACh is metabolised by cholinesterase (ChE) and recycled · Calcium acts as a second messenger

Tissue organisation

· You have connective tissue between the two layers of epithelia. · You have muscle cells between the two layers of fibroblasts (synthesizes the ECM and collagen, produces the structural framework (stroma) for animal tissues, and plays a critical role in wound healing. most common cells of connective tissue in animals.) · Connective Tissue - the cells are isolated and don't tend to touch one another - they don't interact with each other as closely as epithelia.

Sarcomere structure (7 components)

· Z-line defines lateral boundaries of sarcomere · Actin thin filament consists of two twisted a-helices · Myosin - thick filaments --> motor proteins. Has heads which interact with actin · TITIN - VERY LARGE spring like filament - keeps the myosin in place. Titin also goes into part of myosin, has spring-like element but also a straight portion within myosin · Nebulin - large filament associated with actin - doesn't really do anything · CapZ and Tropomodulin - associate with the +ve (near z-line) and -ve (towards middle) ends of actin respectively . Tropomyosin (springlike shape) around actin in diagram

Psoriaris

• Affects 15% of pop • Inflammatory dermatosis not infection • Causes overproliferation of keratinocytes - form inflamed plaques (well-defined salmon pink colour) • Often affects elbows, knees, scalps but can be anywhere • Itchy, sore, disfiguring • Said to affect quality of life similar to diabetes • Patients often have other associated CardioVascular probs e.g. increased risk of diabetes, obesity • Also associated with psoriatic arthiritis • Treatments: topical (cream), light treatment, topical steroids, certain drugs, biological agents

androgenic alopecia

• Androgen Sensitive women can get it too • 50% men over 50y • >80% men over 70y • Polygenic • Treat with • 5α reductase inhibitors/minoxidil

Structure of stratum corneum

• Between corneocytes (terminally differentiated keratinocytes) there's fats and proteins sticking the cells together --> seal and barrier • If defective, skin dry and lets in irritants e.g. allergens causing allergies or eczema, or infections • Part of barrier is made by filagrin protein

How do we achieve thermoregulation?

• Core temp of 36.8 o C • Skin blood flow - Skin temp responsive to blood flow. 1 - 100ml / min per 100g skin. Sympathetic control. Dilate when hot. • Sweating - produced by eccrine glands (watery sweat, present everywhere on body) and apocrine sweat glands (only located in armpit and groins --> produce viscous sweat - has certain chemical that break down and subject to bacterial mechanism --> odour and pheromone), latent heat of vaporisation --> cools skin by evaporation. Max = 0.5L per day; max is 10L per day • Shivering • Behaviour - more clothes

Eczema causes

• Filagrin gene mutation common in eczema patients --> glue that creates barrier is defetcive • Palmar hyperlineraity is a sign of filagrin gene mutation • So if see: itchy skin rash + palmar hyperlinearity --> likely to have eczema due to filagrin gene mutation • Eczema = red, raw , itchy, more likely to get allergies and infected :

Malignant melanoma

• If patient with urgent cancer risk thought, seen in hospital within 2 weeks • Darkly pigmented, lumpy in middle, irregular border • Use dermatoscope to look at it --> can look into lesion (asymmetrical) • Then excised --> sent to pathologist, if see atypical melanocytes = malignant melanoma • Depending on depth of invasion, wide excision (1 - 2cm excess) Also look for signs of spreading to lymph nodes which may require further surgery/chemotherapy

Structure of nails

• Mostly hard "hair" alpha keratin - forms dense plate formed by matrix of nail. . Little Ca2+ • Strong • Longitudinal Ridging • Proximal to distal curvature

Toxic epidermonecrolysis

• Patient had drug, reacted in such a way that immune system makes keratinocytes in epidermis apoptose at same time (keratin) - so it dies and peels off. also involves mucus membranes (mouth, eyes, nose, genital area) • Recognise, refer to hospital, stop drug, supportive care (ITU) - treated as burns patient 70% patients recover, 30% die

Herpes zoster

• Reactivation of chicken pox - patient had chicken pox at some point in life, and varicella zoster lives on in dorsal root ganglions (part of nerve cells in spine) and in times of stress or low immunity it reactivates and reactivates chicken pox along nerve dermatone. • Painful --> rash, blisters, takes 2-3 to heal • Can get ophthalmic division of the trigemminal nerve (supplies foreheads, eyes and eyelids) - can affect sight as well • Treated with acyclovir drug • There is vaccine available for children to prevent chickenpox and also for patients over age 70 who haven't had shingles vaccine to prevent this infection

Collagen and elastin histology

• Skin histology - collagen: pinky fibres = collagen. Can see nuclei of cells: most of these cells are fibroblasts and immune cells. May also see smooth muscle (in bottom RH corner)

What is the dermis?

• Supportive connective tissue matrix • Collagen 70% - strength • Elastin - elasticity • Glycosaminoglycans (GAGs) - gel-like substance that it can all sit in • Fibroblasts - makes the collagen, elastin, GAGs • Immune cells • Varies in thickness (thick on back: 4mm and 0.1mm in eyelids)

Physiological response to hypoglycemia

○ Glucagon is secreted by the alpha cells in the islets of Langerhans in pancreas ○ Glucagon travels out of pancreas in blood vessels ○ Glucagon stimulates gluconeogenesis (only in more extreme hypoglycaemia) and glycogenolysis in the liver --> increasing blood glucose levels This is an example of ENDOCRINE SIGNALLING - hormone travels via the blood and acts on a distant target cell Other examples of endocrine signalling: · Insulin (produced in pancreas acts on liver, muscle cells and adipose tissue) · Adrenaline produced in adrenal glands acting on the trachea and bronchi (dilates airways so more air comes in), also acts on other organs like heart · Prolactin produced by pituitary gland and acting on mammary glands