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 Franklin’s 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

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◦ 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

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▪ 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

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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

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▪ 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