ES173 - Past Paper Content

Body Chemistry and Cell Structure

Characteristics of life Organisation, Cellular composition, Metabolism, Responsiveness and movement, Homeostasis, Development, Reproduction, Evolution (Page 15-16) Organelles Nucleus Largest organelle Contains genetic information Produces RNA Mitochondria Produce energy Endoplasmic reticulum Rough Produces protein Smooth Produces lipids Golgi complex Collects, packages, and distributes molecules which have been synthesised in one place and are needed in another Ribosomes Read mRNA and interpret it Synthesise proteins from amino acids Peroxisomes Neutralise free radicals Detoxify alcohol Lysosomes Contain enzymes Hydrolyse substrates Centrioles Assembly of microtubules which play a role in cell division Size limitations Surface to area ratio decreased for larger cells Diffusion is limited by surface area Enough nutrients must be able to diffuse through the membrane to support the cell Macromolecules Carbohydrates Source of energy (and membrane components) Lipids Source of energy Energy storage Cell membrane components Chemical messengers Coating of nerve cells Proteins Function determined by shape Provide structure (collagen) Communication Membrane transport Recognition and protection (antigens and antibodies)

Cell adhesion (cell adhesion molecules) Catalysis (enzymes) Nucleic acids Genetic code (DNA) Instruction carriers (RNA) Energy carriers (ATP/ADP) Homeostasis The tendency of a living body to maintain relatively stable internal conditions in spite of greater changes in its external environment Na+- K+ pump Protein pump which uses ATP to pump 3 Na+ out of a cell, and 2 K+ into the cell Functions Regulates cell volume reduces osmotic pressure Cell anions attract cations and cause osmosis Pumps open when cell swells Maintains a steep concentration gradient of Na+ and K+ Secondary active transport Symporters move Na+ into cells along with a second solute Heat production Maintains resting membrane potential Essential for nerve and muscle function Negative inside cell, positive outside cell Cellular metabolism Glucose Pyruvic acid + 2 ATP Anaerobic Pyruvic acid Lactic acid Aerobic Pyruvic acid CO2 + H2O + 36 ATP Visualisation instruments Compound microscopes Transmission electron microscopes Scanning electron microscopes Contrast improvement in microscopy Polarised light Used on specimen which exhibit double refraction Phase contrast imaging Small phase shifts in the light transmitted through the specimen are converted to amplitude or contrast changes in the image Differential interference contrast Polarised light is split into two rays which are polarised at 90o to each other Rays pass through the specimen at a slight separation Rays are recombined into one, which results in an interference pattern representing the difference between adjacent areas of the image Fluorescence illumination Specimen illuminated by one wavelength of light Another, longer, wavelength of light is produced by the specimen Dark field illumination Unscattered light is not used to produce the image, only the light scattered by the specimen Leads to a black background Rheinberg illumination Similar to dark field illumination, but coloured filters are used and so coloured backgrounds and higher contrast result

Hoffman modulation contrast Phase gradients are converted to variation in light intensity Gives 3d appearance Optical fibres AFM Uses a probe attached to a cantilever Probe usually just a few atoms wide at the tip Scanned over the surface, repelled by the electron shells of the atoms in the specimen Achieves atomic resolution STM Relies on quantum tunnelling Voltage bias between specimen and probe Probe is scanned across the surface Electrons tunnel from the probe to the specimen and the current is measured Achieves atomic resolution Nucleotide components Phosphate group Ribose sugar (RNA), or deoxyribose sugar (DNA) Nitrogenous base Major parts of a cell Genetic material Stores hereditary information in the cell Cytoplasm Fills the cell interior Plasma membrane Encloses the cell Provides control over entry and exit of substances

DNA
Natural selection Some individuals have hereditary advantages over others Advantages which aid survival increase reproductive success, and so those genes passed on Darwin was inspired by the variations between beaks of finches on the Galapagos Islands Each was adapted to suit the food that was available for the bird Evolution Through time, species accumulate differences; as a result, when new species are formed, the descendent species differ from their ancestors Charles Darwin Genetic mutation Occur due to imperfect nature of DNA replication Segments may be repeated or deleted Crossing over of DNA during meiosis Single nucleotides can be altered during replication Can occur due to environmental factors such as radiation, chemicals, or viruses DNA Deoxyribonucleic acid Nucleotides are bonded via phosphate-sugar bonds and also by hydrogen bonds with their complementary base Twisted ladder - double alpha-helix Store of genetic information RNA Ribonucleic acid

Nucleotides bonded together via phosphate-sugar bonds Usually single stranded with a complex 3d shape Uracil instead of thymine mRNA carries information that directs protein synthesis ATP Adenosine triphosphate Store of chemical energy Produced from ADP during respiration, used during any process requiring energy Determination of DNA sequence Fluorescently labelled dideoxyribonucleic acids stop the polymerase enzyme from continuing on the strand Electrophoresis then used to determine the lengths at which the polymerase stopped at each specific nucleotide Electrophoresis Uses an applied electric field to separate DNA fragments by size Utilises fluorescent markers at the end of DNA fragments to visualise the locations on the gel DNA replication Semi-conservative DNA spilt into single strands by DNA helicase Single Strand Bonding proteins prevent DNA from reannealing Primase synthesises the short RNA sequences needed to start replication Polymerase then replicates the DNA using the complementary bases DNA is replicates continuously on the leading strand, and discontinuously on the lagging strand Synthesis in the 5 to 3 direction (of new strand) RNase H removes the RNA strands which began the synthesis DNA ligase links short stretches together to form one long continuous strand DNA amplification PCR Amplified short sections of DNA DNA is split into single strands by heating, and is then replicated Uses Taq polymerase to allow DNA to be amplified exponentially LightCycler Commercial automated implementation of PCR Rapid cycling and simultaneous closed tube detection AFM in DNA sequencing DNA immobilised on either glass or gold and is placed under water The probe is tapped up and down to avoid damaging the DNA as it is scans Atomic resolution is achieved and the DNA sequence can be interpreted Rosalind Franklin Discovered that the phosphate groups were on the outside of the DNA molecule Created the x-ray crystallography photos which Watson and Crick used to determine the structure of DNA Watson and Crick Determined the structure of DNA from Rosalind Franklins photos Created a model of the DNA structure

Circulation and Respiration

Major parts of circulation system Lymphatic System Lymph nodes Garrisons of B, T and other immune cells

Act as filters for foreign particles Lymph capillaries Tiny thin walled tubes which are spread throughout the body (except the central nervous system and non-vascular tissues) Drain excess fluid from tissues Interstitial fluid can flow into them but not out of them Attached to the surrounding tissue by elastic fibres which extend from the endothelial cells Lymph trunks Carries lymph from efferent lymph vessels Drains lymph into one of two lymph ducts Vascular System Heart Pulmonary circuit Right side of the heart Supplies blood to the lungs for gas exchange Systemic circuit Left side of heart Supplies blood to all organs Arteries Arterioles Capillaries Diffusion through endothelium Lipid soluble substances Steriods, O2, and CO2 Diffuse easily Lipid insoluble substances Glucose and electrolytes Must pass through channels, fenestrations (proteins) or intercellular clefts Large particles Large proteins are held back Transcytosis Fatty acids, albumin, some hormones (insulin) Filtration and reabsorption Venules Veins Routing of blood flow Contraction of smooth muscle layer causes vasoconstriction which increase resistance and decreases blood flow Pressure downstream decreases, upstream pressure increases Relaxation of smooth muscle layer causes vasodilation which decreases resistance and increases blood flow Blood routing mainly controlled by arterioles as they are numerous, and more muscular by diameter Pulse oximetry Operation Uses selected wavelength of light to determine the saturation of oxygen Pulsatile signal generated by arterial blood What is measured? Directly measures the amount of light at specific wavelengths which is absorbed Indirectly measures pulse rate and oxygen saturation levels

Basis of measurement Limitations Motion artifacts Intravascular dyes Exposure to ambient light during operation Skin pigmentation Nail polish Less accurate below 83% saturation Cannot quantitate hyperoxemia False negatives for hypoxemia Cannot be used on patients who have inhaled smoke as the probe cannot distinguish between carboxyhaemoglobin and oxyhaemoglobin. High levels of methaemoglobin (haemoglobin with Fe3+ instead of Fe2+)cause the probe to read 85% regardless of actual oxygen saturation. Falsepositives for normoxmeia or hyperoxemia Probe misuse Pressure sores Electrical shocks Congenitally corrected transposition Can cause fainting and fatigue Influencing factors of diffusion Surface area Concentration gradient Membrane permeability Molecular weight Temperature

Organs and Visualisation

Organ systems Regulation and Maintenance Digestive system Circulatory system Respiratory system Urinary system Lymphatic and immune systems Support and Movement Skeletal system Skeletal muscular system Integumentary system Integration and Control Nervous system Endocrine system Reproduction and Development Reproductive system Resolution The smallest distance between two points on a specimen which can be distinguished as being separate entities Magnification Relative size of the image compared to the specimen Endoscopy Construction

Rigid or flexible tube Light source usually delivered via non-coherent bundles of optical fibres Either a lens system as in rigid endoscope, or a bundle or coherent optical fibres in the case of flexible endoscopes Eye piece or CCD camera Additional channel for tools to be inserted Operation A small incision can be made if necessary, then the endoscope is inserted into the body The physician views the image produced for the purpose of diagnosis or surgery Use Used to look inside the body either through an opening in the body such as the mouth or anus, or through a small incision Advantages Only a small incision is required Pill camera Small camera fitted inside a transparent capsule Capsule contains its own light source, and some means of powering it The capsule is swallowed and relays its image via radio waves Allows for a video of the journey through the digestive tract to be recorded OCT Similar to ultrasound, but uses light instead of sound A broad spectrum of light is split into a sample arm and a reference arm By combining the reflected light from the sample with the reference light, an interference pattern can be formed Scanning the mirror allows for a reflectivity profile of the sample to be produced (time domain OCT) Tissue Definition An aggregation of cells and extracellular materials, usually forming part of an organ and performing some discrete function for it Types Epithelial One or more layers of closely adhering cells Flat sheet at the surface exposed to the environment or an internal cavity No blood vessels Specialised into glands (exocrine and endocrine) Exocrine Endocrine Sits on basement membrane Connective Widely space cells connected by fibres and ground substance Most abundant and variable type Examples: Tendons Bone, cartilage, lymphatic system Bone is a calcified matrix of concentric lamellae around central (Haversian) canals containing blood vessels Osteocytes in lacunae between lamellae, connected by canalculi Adipose tissue Blood (Fibres in soluble form polymerise when they leak. Ground substance is plasma)

 Muscle Elongated cells that respond to stimuli by contracting Exert physical force on other tissues Source of body heat 3 types: skeletal cardiac smooth Nerve Neurons and neuroglia For internal communication between cells Found in brain, spinal cord, nerves, and ganglia

Medical Imaging
PET Positron emission tomography A positron-emitting tracer is introduced to the body on a biologically active molecule The radioactive decay of the tracer leads to the emission of pairs of gamma rays Computer analysis is then used to determine the position of the tracer and the concentration of the biologically active molecule Photons not arriving in temporal pairs are ignored Photons are emitted at almost 180o and so their origin can be determined to with a reasonable degree of precision CT X-ray computer tomography Generate a 3d image from a series of 2d images taken around a single axis Contrast agents can be used to highlight blood vessels MRI Magnetic resonance imaging MRI scanners use a strong uniform magnetic field combined with a gradient field to align the magnetic moments of hydrogen nuclei in water An RF transmitter is used to flip some of the magnetic moments so that they are in anti-parallel with the magnetic field The hydrogen nuclei then return to their low energy state and release this energy in a photon Frequency of emitted photon is dependent on the position within the magnetic field fMRI Used to show the change in blood flow related to neural activity in the brain or spinal cord MRI is sensitive to the change in oxygen concentration changes Ultrasonic Used to visualise subcutaneous body structures such as tendons, muscles, joints, vessels, internal organs, and foetuses An ultrasound pulse is sent out and is reflected at boundaries between tissues of different acoustic impedances The time delay before pulse is returned is dependant upon the penetration depth, and so the depth of the boundaries can be found Functional imaging (define) The in vivo diagnosis of physiological states and of dynamic processes, such as metabolism and blood flow, by imaging

Prosthesis and Biomimicking

Two examples

Function Requirements History Cost Materials Manufacture Usage constraints Lifetime

Bones, Muscles and Diagnostic Instrumentation

Striated muscle Skeletal muscle Voluntary control Attached to bone Universal characteristics of muscle Responsiveness Responsive to chemical and electrical signals Conductivity Local electrical change triggers a wave of excitation Contractibility Extensibility Elasticity EMG Surface pads or intramuscular needles Measures the electrical activity of skeletal muscle Cardiac Cycle Ventricular filling AV valve opens and blood fills ventricle Atrial systole occurs and forces more blood into the ventricles Isovolumetric contraction Atria remain in diastole for the remainder of the cycle Ventricles depolarise and generate QRS complex AV valves close Ventricular ejection Ejection of blood begins Not all blood is ejected Isovolumetric relaxation Ventricular diastole Slight pressure rebound Diagnosis of Heart problems Mixture of ultrasound, ECG, chest x-rays, and MRI/CT ECG Numerous pad placed around the body at key points Detects and amplifies tiny electrical changes caused when the heart depolarises in each cycle Produces a trace of heart activity EMS Electrical muscle stimulation Electrical impulses mimic action potentials from the CNS and so stimulate the muscle Bike for disabled Belts around the legs

Synchronised pulses in a set pattern so that the muscles contract in the correct sequence to cycle the pedals Provides better exercise than stationary EMS Joint types (Page 287) Diarthrosis Freely moveable Amphiarthrosis Slightly moveable Synarthrosis Little or no movement Fibrous Collagen fibres between two bones Joint between palatine processes in the roof of the mouth Cartilaginous Two bones bound by cartilage Intervertebral discs of fibrocartilage Bony Two bones joined by osseous tissue Right and left mandible bones fused together Synovial Bones separated by fluid filled space Knee, hip, elbow, finger joints Weakness in astronauts Bone volume decreases Muscle volume decreases Changes due to reduced loading in zero gravity Four roles of skeletal muscles Movement Posture Joint stability Heat production

Brain and Nervous System

Structure of nerve cell Dendrites Soma (cell body) with nucleus Axon which may be wrapped by myelin sheath (due to Schwann cells) with nodes of Ranvier in the gaps in the myelin sheath Ends with synaptic knobs Fundamental properties Excitability Respond to changes in the body and external environment (stimuli) Conductivity Produce and propagate electrical signals Secretion Chemical neurotransmitter secreted when the signal reaches the end of the fibre Conduction in nerves Resting potential Maintained by Na+-K+ pumps, voltage-gated ion channels, and large negatively charged molecules Negative on inside, positive on the outside

Action potential When activated, voltage-gated ion channels become more permeable and Na+ rushes into the cell Cell depolarised by influx of positive charges Causes a chain reaction to propagate down the axon Unmyelinated fibres Self-propagating action potential propagates down the length of the axon Influx of Na+ depolarises the adjacent length, and so generates a new action potential Myelinated fibres Myelin sheath insulates sections and so impulse travels by Na+ diffusing along the axon and depolarising the node of Ranvier to produce a new action potential Decremental and so nodes are needed at least every millimetre Comparison of nerves to electrical wires Nerves are digital, wires are analogue Current flow is longitudinal in wires, and transverse in nerves Transmission speed Depends on diameter and presence of myelin Large myelinated nerves are faster EMG to diagnose problems For intramuscular EMG, the output is monitored as the needles are inserted because the muscles react electrically The electrical activity when the muscles are inactive should be zero the presence of spontaneous signals suggests that there is a problem EEG Records the electrical signals in the scalp PAGE 538 ERP Effective refractory period Once an action potential has been initiated, there is a period of time for which another action potential cannot be generated Local Anaesthetics Blocking of Na+ gates Prevents depolarisation Stops the generation and propagation of action potentials Local anaesthetics occupy the Na+ channel and inhibit the rapid influx of Na+ Significance of squid to transmission Large neurons which could easily be isolated Larger, but similar in nature to human nerve cells Large enough for electrodes to be inserted in order to measure the membrane potential Phineas Gage Had a bar blasted through his skull and damaged the left frontal lobe Had impaired planning, mood and social judgement Influenced 19th Century thinking about cerebral localisation of functions Demonstrated that the frontal lobe controls these things