Neuro/Muscle SAQs Q&A PDF

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StimulatingRubellite7172

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Trinity College Dublin

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This document contains sample questions and answers related to neurobiology and physiology. It includes details about different types of ion channels and action potentials. It may be part of an upcoming exam or past exam paper for students to practice.

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NEURO/MUSCLE Concept tested What to cover CHANNEL TYPES 1. VOLTAGE GATED ION CHANNELS Ion channels can be - Opens and closes in response to membrane potential changes, usually opens gated by different with depolarisation of membrane mechanisms, name 2...

NEURO/MUSCLE Concept tested What to cover CHANNEL TYPES 1. VOLTAGE GATED ION CHANNELS Ion channels can be - Opens and closes in response to membrane potential changes, usually opens gated by different with depolarisation of membrane mechanisms, name 2 - Example: Ca2+ voltage-gated ion channels in the presynaptic button, and its types in neurons and function is to allow the influx of Ca2+ ions into the presynaptic button to give 1 example of each stimulate the synaptic vesicles containing neurotransmitters to fuse with the and its function (2017) presynaptic membrane, and release the neurotransmitters via exocytosis 2. LIGAND GATED ION CHANNELS - Opens and closes in response to ligand binding to receptor - Example: ionotropic glutamate receptor, NMDA receptor, which function is to permit the entry of Ca2+, and this is important in synaptic plasticity (LTP), plays a role in learning and memory 3. MECHANICALLY GATED ION CHANNELS - Open and closes in response to physical mechanical deformation - Example: pacinian corpuscle, which function in the formation of sensory response from a stimulus (eg the formation of a response to physical touch of skin) - Another example: the stereocilia on inner hair cells in the ear contains mechanically gated ion channels which open to allow the influx of K+ causing depolarisation Voltage gated ion = class of transmembrane proteins that form ion channels that activates / opens in channels and 3 types response to changes in membrane potential, usually depolarisation (2015) Calcium voltage-gated ion channels can be found in presynaptic button Na+, K+ and Cl-voltage gated ion channels can all be found in the cell membrane, at the axon hillock and the nodes of ranvier of the neuron ACTION POTENTIAL Describe the key processes which allow for the propagation of action potential along the axon (2019) STEPS: 1. Voltage-gated Na+ and K+ ion channels are closed in resting state 2. When stimulus present, some Na+ channels open, causing cell to be more positive, there is some local membrane depolarisation, bringing membrane potential from resting to threshold potential 3. Depolarisation occurs; voltage-gated Na+ ion channels increase the membrane permeability of Na+, membrane potential increases quickly towards equilibrium potential of Na+. Peak of AP only reaches about +30mV because voltage-gated K+ channels are also opening but slowly. 4. At peak potential, Na+ channel closes, but voltage-gated K+ channels still open 5. Repolarisation, efflux of K+ causes the membrane potential to fall back towards resting membrane potential 6. Hyperpolarization, Na+ gates are closed, K+ still open, the continued efflux of K+ keeps membrane potential below resting membrane potential 7. Voltage-gated K+ channels gradually close, causing both Na+ and K+ permeability to return to the resting state, the Na/K ATPase pump will then rapidly correct the tiny quantities of Na and K+ concentration, restoring RMP! After an AP is generated, it can travel down an unmyelinated to myelinated axon. UNMYELINATED - AP travels down axon via contiguous conduction, where regeneration of AP occurs continuously along the length axon, is self-propagated MYELINATED - sheaths of myelin surround the axon and are separated by myelin-free gaps called nodes of Ranvier. Myelin decreases membrane capacitance, increases membrane resistance, most of the change in membrane permeability at nodes, which contain high concentration of voltage-gated Na+ channels, allows for regeneration of AP as it travels down the axon, ‘jumping between NOR’, saltatory conduction. Factors affecting the Larger diameter = nerve conduction speed - greater total volume for electric currents to flow through, so LOWER INTERNAL RESISTANCE - contains more ion channels → LOWER MEMBRANE RESISTANCE to current flow, reach THRESHOLD at LOWER stimulation voltage, hence conduction of AP is faster Myelin = - insulate the axon, REDUCED ELECTRICAL LEAKAGE ACROSS MEMB. - HIGHER MEMBRANE RESISTANCE to current flow - Nodes contain a high concentration of Na+ channels which allow regeneration of the AP along the axon, current flows almost totally at the nodes of Ranvier, saltatory conduction Absolute and relative Absolute refractory period refractory periods Membrane is completely resistant to further stimulation. No matter how strongly the membrane is stimulated, another AP will not fire As voltage-gated Na+ channels – "voltage-gated" properties means that they are in different states (open / closed / inactivated) @ different voltages. Large number of these Na channels are voltage-inactivated, and will only open again when the cell enters the relative refractory period (depolarisation) Relative refractory period Membrane is more resistant to stimulation than usual Some voltage-gated Na+ channels still inactivated, so stronger stimulus than usual is required to open a sufficient number of these channels for another AP to fire Cell membrane is more permeable to K+ during this period ⇒ further opposes depolarization of the membrane (hyperpolarisation ?? IDK period) EPSP/IPSP + sum GLUTAMATE = major excitatory neurotransmitter in the CNS, acts on both C&C glutamate and metabotropic and ionotropic receptors GABA receptors in the - Ionotropic: forms an ion channel pore CNS (2019) There are 2 types of ionotropic glutamate receptors (AMPAR and NMDAR) Metabotropic and AMPAR: chemically mediated receptor channel that opens on the binding of glutamate, ionotropic permits entry of Na+, leading to formation of EPSP at postsynaptic neuron. NMDAR: receptor channel that permits Ca2+ entry when open, coexists with AMPAR postsynaptically, but stronger presynaptic stimulation is required to activate it. But NMDAR is closed both by a gate and a Mg ion which physically blocks the channel opening at resting potential, gate opens on binding to glutamate but additional depolarisation beyond normal is needed to force Mg2+ out of the channel. **thus AMPAR has faster reaction, NMDAR slower reaction - Metabotropic: indirectly linked with ion channels on plasma membrane of the cell, through signal transduction mechanisms, such as G proteins AP causes glutamate release from presynaptic, which binds to postsynaptic receptors and opens a channel in the centre of the receptor. Na influx opens channels, and generates a small amplitude of depolarising EPSP GABA = primary inhibitory transmitter, can act on AMPA and NMDA to evoke an inhibitory postsynaptic response (IPSP) and hyperpolarisation. Inhibitory synaptic transmission allows control and regulation of excitement, preventing over excitement. Postsynaptic potentials can be excitatory (EPSPs), or inhibitory (IPSPs) Postsynaptic potentials TEMPORAL SUMMATION = sum of several EPSPs due to the successful firing from a Describe (i) temporal single presynaptic neuron, the 2nd action potential occurs when the postsynaptic and (ii) spatial (2015, membrane is partially depolarised, graded potentials have no refractory periods, so the 2017) 2nd EPSP is added onto the 1st EPSP, and summation occurs SPATIAL SUMMATION = sum of several EPSPs from several different presynaptic terminals firing simultaneously. These can both occur with EPSPs and IPSP, but all of the postsynaptic potentials must be excitatory or inhibitory, not a mix of both, to meet the threshold and create an AP in the postsynaptic neuron. C&C EPSPs and IPSPs EPSPs: Excitatory potential, opens non-specific cation channels, in the subsynaptic (2014) membrane, allowing the passage of Na and K ions, large amounts of Na+ enters, small amount K+ exits, causing a small depolarisation of the postsynaptic membrane, bringing it closer to threshold, making it more excitable IPSPs: Inhibitory potential, opens the receptor channels for K+ and Cl-, influx of Cl- EPSP diagram (2012) efflux of K+ makes the membrane more negative, causing small hyperpolarisation, postsynaptic membrane further from threshold, making it less excitable C&C synaptic potential and action potential Synaptic potential Action potential (2016) Graded potential Refractory period None Absolute or relative refractory (2010) Summation Temporal or spatial None Direction of Can be de- or hyper- ALWAYS DEPOLARISATION and potential change polarised (EPSP/IPSP) reversal of charges Mag of potential Decremental conduction; Propagated through membrane change with magnitude diminishes undiminishing, self-regenerated in distance from initial with distance fr initial site neighbouring inactive area of site membrane Effects of Graded potential change: ALL OR NONE response: magnitude of the magnitude varies with magnitude of triggering event is triggering event magnitude of triggering coded in frequency rather than events amplitude of AP = local change in membrane potential that occurs in varying grades of different degrees of magnitude in specialised membranes. Types of graded potential can be divided into EPSPs and IPSP (see above) CLINICAL Both condition prevents the release of neurotransmitters and hence inhibits normal C&C mechanisms muscular function underlying tetanus and (see table below) summary: Tetanus is the thing preventing inhibitory GABA release, botulinum (2020) botulinum is a toxin preventing ACh release. Describe & explain clinical consequences of Impairment of NM synapses = inability to generate an AP, in the motor end plate of impairments in the the cell. Long-term lack of stimulation of the muscle will eventually lead to muscular function of dystrophy. neuromuscular (see table below) summary: Myasthenia gravis where AChR attacked and destroyed, synapses (2020) Lambert eaton where the voltage gated Ca2+ channels affected, Ca cannot go in Describe the role of Ca2+ on the smooth muscle contraction and the biochemical differences with skeletal muscle contraction (2020) Comparing smooth and skeletal muscles: Smooth – Myosin head can only interact with phosphorylated myosin light chain, increased in systolic Ca2+ acts as an intracellular messenger. 1. Ca2+ binds with calmodulin, forming Ca-calmodulin complex 2. Binds to and activates myosin light chain kinase 3. Phosphorylates the inactive light chain, activating it and allowing myosin head to bind to actin, crossbridge cycling can occur, initiating muscle contraction Ca2+ induces a chemical change in myosin in the thick filaments Skeletal – (1. Ca2+ binds to TnC of troponin, induces a conformational change in the troponin-tropomyosin complex 2. Complex pulls aways and exposes the myosin-binding sites on the actin 3. Cross-bridging can occur) Ca2+ binding to troponin and tropomyosin induces a physical change (pulling away) at the actin thin filaments Both: rise in cytosolic Ca2+ triggers smooth and skeletal contraction Cardiac muscles have both skeletal and smooth muscle features Describe the structural Skeletal feature: and function Striated, have thick filaments that are highly organised into banding patterns, characteristics of and thin filaments contain troponin and tropomyosin, which is the site of Ca2+ cardiac muscles (2019) action to initiate cross bridging activity Alot of mitochondria, and myoglobin, because its constantly working and requires a large amount of energy Has transverse tubules and moderately well-developed sarcoplasmic reticulum for Ca2+ release Smooth feature: Cardiac muscle is slender and short, and display pacemaker activity which allows it to initiate AP without external influences Interconnected by gap junction which enhances the spread of AP Cardiac muscle fibres are joined in a branching network and have a much longer AP before repolarisation MUSCLE SPINDLES Muscle spindles consists of muscle fibres called intrafusal muscle fibres, each muscle How muscle spindles spindle has it own private afferent and efferent nerve supply, intrafusal fibres are (stretch receptors) supplied by the gamma motor neuron (efferent) while the extrafusal fibres are supplied contribute to the stretch by the alpha motor neuron (efferent) reflex (2017) STRETCH REFLEX = when the muscle is passively stretched, the intrafusal muscle spindles are stretched as well, and this causes a depolarisation of 1a sensory axons Describe the anatomy of via mechanosensitive ion channels (increasing firing rate?) muscle spindle fibres → Afferent neuron (from the 1a) directly synapses to the alpha motor neuron that and explain their innervates the extrafusal muscle fibres on the same muscle, causing a contraction of physiological role in the muscle fibres. muscle contraction → local negative feedback mechanism that resists any passive change to muscle length, so that optimal resting muscle length can be maintained Patella tendon (knee jerk) reflex Tapping of patella tendon passively stretches the muscle spindle of quadriceps, stimulating its 1a sensory axons. The resulting stretch reflex is the contraction of the quadriceps femoris, raising leg up and causing extension of knee. (test done to measure the normal activities of motor neuron, afferent input, muscle spindle and efferent output) C&C primary and secondary endings Primary endings Secondary endings (2018, 2013) annulospiral and flower Anatomical/location Wrapped around central Clustered @ end segment spray portion of intrafusal fibres of intrafusal fibres Function / stimulus to Detects changes in length Sensitive only to changes induce response during stretch and speed at in length of muscle fibres which it occurs Resting discharge rate 10/s 10/s Max AP frequency 500 per second 50 per second following rapid stretch Adaptation Phasic (rapid) Tonic (slow) There are 2 types of muscle fibres: intrafusal and extrafusal fibres. Intrafusal fibres lie within spindle connective tissue capsules, parallel to extrafusal fibres. Compare structural and functional differences of intra and extrafusal Intrafusal Extrafusal fibres (2012, 2020) Structure: Contractile elements limited to Contractile elements throughout ends of muscle spindle, entire length of muscle fibre non-contractile central Efferent: Innervated by gamma motor Innervated by alpha motor neuron neuron Afferent: Type 1a sensory axons wrap around central portion, detects rate, change of length Type 1b sensory axons clustered at end segments, sensitive to changes in length Function: Serves as proprioceptors Affected by stretch reflex Detect the amount and rate of Contracts to resist any passive change in muscle length changes in muscle length, optimal Activates stretch reflex length of muscle can maintained (coactivation of gamma and motor neurons) Motor unit recruitment One motor neuron innervates a number of muscle fibres, but each muscle fibre is only supplied by 1 motor neuron Motor unit: motor neuron and all the muscle fibres it innervates, the muscle fibres innervated by the same motor neuron are dispersed in a muscle, so the simultaneous contraction will result in an evenly-distributed contraction. Stronger contractions = more motor units recruited Small motor fibres = fine control over muscle tension, larger motor fibres (in bigger muscles) = large incremental increase in muscle tension, more powerful and less precisely controlled gradations Number of muscle fibres participating in whole muscle contraction depends on number of motor unit recruitment and number of muscle fibres in that muscle Asynchronous recruitment of motor units takes place to delay/prevent fatigue during sustained contraction, body alternates MU activity - Only for submaximal contractions - During maximal: all MU participate, cannot alternate Comparison between parasympathetic and sympathetic (ANS) Name 2 peripheral chemoreceptors. Draw a flow diagram to illustrate how activation of 1 of these receptors transduces its adequate stimulus and transmits it to the CNS. (2017/2018) From generation of action potential at NMJ to depolarisation of MEP to muscle contraction complete version 1. Propagation of AP to terminal axon button triggers the opening of Ca2+ voltage gated channels on the presynaptic button membrane 2. Ca2+ channels open, influx of Ca2+ 3. Ca2+ triggers the exocytosis of synaptic vesicles containing neurotransmitters (acetylcholine, ACh) into the synaptic cleft 4. ACh diffuses across the synaptic cleft, and binds to the nicotinic ACh receptor on the motor end plate of the muscle membrane 5. Non-specific cation channels open, causing the movement of Na and K ions (Na+ influx, K efflux) but the rate of Na influx is much faster than the K efflux because the greater electrochemical gradient drives Na+ in 6. Depolarisation of the motor end plate causes a slight membrane potential change called the end-plate potential (EPP) 7. EPP generated, bidirectional local current flow from the depolarised end plate to the adjacent resting cell membrane via contiguous conduction 8. Depolarisation causes the opening of voltage-gated Na channels, influx of Na+ further depolarises the membrane, making it more positive to threshold potential 9. Upon reaching threshold potential, an ACTION POTENTIAL is initiated 10. AP is propagated along the sarcolemma, and moves down the T tubules 11. Depolarisation of the T tubules activates the dihydropyridine (DHP) receptors which opens the ryanodine (RyR) which are complementarity bound to each other 12. Some of the Ca2+ releasing channels in direct contact with the DHP release Ca2+ from the lateral sacs of the sarcoplasmic reticulum into the sarcoplasm 13. The influx of Ca2+ into the cytosol activates the rest of the Ca2+ releasing channels, then activates the rest of the RyR channels that are not bound to DHP to open, causing all the Ca2+ releasing channels to open 14. Ca2+ binds to troponin (TnC of troponin) 15. ATP binds to the ATP binding site on myosin and is broken down into ADP and Pi by ATPase activity, and energy from ATP breakdown is stored in the myosin head, ‘cocking it’, ADP and Pi remain attached to the myosin head 16. When the muscle is at rest, tropomyosin blocks myosin from binding in the myosin-binding site of actin, but the binding of Ca to the troponin causes a conformational change to troponin, causing it to pull the troponin-tropomyosin complex away from the actin, exposing the myosin binding site 17. Cross bridge form and myosin is bound to actin 18. After binding, the myosin head bends, releasing energy through the power stroke and cross bridge also bends, pulling the thin filament towards the centre of the sarcomere. During this, the Pi dissociates from the myosin 19. The muscle shortens, and ADP dissociates, myosin head returns to its original state, awaiting another ATP molecule to bind to its ATP binding site 20. As this happened throughout the sarcomere, sarcomere shortens and muscle contracts, Z and M lines drawn closer together. When muscle fibres contract in unison, muscle fibre can produce enough force to move a body. DISEASE WHAT IT IS EFFECTS Multiple Autoimmune condition, where the body’s defence Slower transmission, interfere with and sclerosis system erroneously attacks the myelin sheath eventually block propagation of AP Fatigue, dizziness, Myasthenia Autoimmune condition where the body erroneously Less ACh able to find a functional receptor to gravis makes acetylcholine receptor (anti-nAChR) bind to and contribute to the motor end-plate antibodies, which competes with ACh to bind to potential, leading to muscle weakness. nicotinic acetylcholine receptors Small end plate potential generated, + Antibodies also complement fixation and subthreshold, lesser AP in muscles, reduced receptor destruction, leading to less available contractile forces, muscle weakness receptors for ACh to bind to - over time, the perpetual lack of stimulation of the muscle then leads to muscular dystrophy Lambert- Autoimmune condition which affects voltage gated Lesser/ no synaptic vesicles fuse with synaptic Eaton Ca2+ channels on the synaptic knob. Ca2+ crucial membrane to release ACh into the synaptic to trigger the release of neurotransmitter so EPP cleft can be generated in the muscle cell - lack of muscular stimulation leads to muscular dystrophy in the long-term Tetanus Caused by bacterial infection Leads to rapid stimulation of muscle fibres Prevents inhibitory neurotransmitter release such that it does not have sufficient (GABA) opportunity to relax between each stimuli, resulting in maximal sustained contraction of → unopposed muscle contractions muscle - respiratory failure due to respiratory muscular spasm Botulinum Caused by consumption of botulinum toxin from Leads to failure of muscles responding to toxin contaminated source nerve impulses Blocks the release of acetylcholine at the - respiratory failure due to inability to contract neuromuscular junction diaphragm muscle SENSORY Concept tested What to cover What is sensory Sensory adaptation: is the decline of receptor potential over time in spite of continued adaptation, and draw 2 stimulation figures illustrating the difference in AP and generator potential as a result from a (i) slowly adapting and (ii) rapidly adapting receptor (2017) 1) slow adapting TONIC receptor - receptors are important in situation where it is valuable to maintain information about a stimulus (eg muscle stretch receptors that monitor length) 2) fast adapting PHASIC receptor - do not respond to a maintained stimulus (smell) What are the different adaptation 1. MECHANICAL ; physical mechanical mechanisms that induces the decrease in the mechanisms response of a receptor neuron (for e.g., pacinian corpuscle responds to vibration and deep pressure is rapidly adapting) 2. CHEMICAL ; membrane enzymes or intracellular signalling mechanisms that induces a response termination (common is olfactory response) What are the different A receptor may either be a specialised ending of a primary afferent neuron or a types of receptor separate receptor cell closely associated with the peripheral ending of the neuron. The transduction stimulation of a receptor causes the opening of non-specific cation channels; an influx of cations causes depolarisation of the receptor. This depolarisation is a graded potential. The larger the graded (receptor) potential, the greater the frequency of AP generated in the afferent neuron. Receptor and generator potential initiates an action potential in the afferent neuron - RECEPTOR POTENTIAL: occurs in separate receptor cells Pathway: voltage gated Ca2+ channels opens as a result of receptor potential → influx of Ca2+ causes release of neurotransmitter that diffuses across the synaptic cleft → binds to the specific receptor proteins on the membrane of the afferent neuron, and causes the opening of ligand-gated Na+ channels → Na+ influx causes depolarisation, which opens the voltage-gated Na+ channels in the adjacent regions → initiation of AP which propagates down the afferent fibres to the CNS - GENERATOR POTENTIAL: occurs in specialised nerve endings of afferent neuron Pathway: stimulus opens ion channels in the receptor, causing local current flow → local current flow causes depolarisation of membrane → depolarisation of adjacent membrane beside the receptor opens the voltage-gated Na+ channels (if threshold is met) → Na+ entry then initiates AP in afferent fibres that self propagates to CNS In myelinated afferent fibres, the trigger zone is the NOR closest to the receptor. What are the criteria for 1. The receptor must be specific to the stimulus energy transduction in a 2. Receptor’s receptive field must be stimulated receptor (sample) 3. The stimulus energy must be converted into a graded potential in the receptor 4. The generator potential in the associated sensory neuron must reach threshold What is the ‘all or ‘ALL OR NOTHING’ = states that an excitable membrane may either respond to a nothing’ law? (???) triggering event with maximal action potential that is spread nondecrementally through the membrane or does not respond with an action potential at all. At low stimulus strength, the memb potential will not be How stimulus strength depolarised to threshold potential and hence no action related to action potential is generated. potential firing (2016) As the strength of the stimulus is strong enough for the membrane potential to reach threshold potential, an AP will be generated. Any more increase in stimulus strength will produce the same maximal magnitude of action potential and will not increase it. Proprioception Proprioceptors detect the position of the body in space, particularly the position of body limbs, to control the skeletal muscle contraction and achieve desired movement 2 main proprioceptive sense organs are golgi tendon and muscle spindle organs, both monitor changes in muscle length and tension. Muscle length monitored by muscle spindles while change in muscle tension is detected by golgi tendon organs (to prevent tendon avulsion?) Lateral inhibition and the LATERAL INHIBITION = where surrounding receptive fields of stimulus are also key features that stimulated but to a lesser extent to better localise the stimulated area. underlie it (2015. - Each activated signal pathway inhibits the pathway next to it by stimulating 2019)** inhibitory interneurons that pass laterally between ascending fibres that are serving neighbouring receptive fields - The most strongly activated pathway originating from the centre of the stimulated area inhibits the surrounding less excited pathways to a greater extent - Compared to the inhibition by the weakly stimulated receptors surrounding the most strongly activated receptors Thus, lateral inhibition enhances contrast btwn areas of strong and weak inhibition Different TOUCH somatosensory - Mechanoreceptors, Ab fibres pathways (C&C) touch - Dorsal Column Medial Lemniscal pathway: dorsal root travelling through the & nociception (sample, dorsal column ipsilateral in the spinal cord, then first synapses in the brain stem, 2022) and crosses midline to the thalamus PAIN - Nociceptors, Ad and C fibres - Spinothalamic pathway: dorsal root, first synapses with a 2nd order neuron that crosses the midline in spinal cord, ascends contralaterally until thalamus COMMON: peripheral receptors, primary afferent fibre synapses with secondary fibre in the CNS, relays in the thalamus and reaches the somatosensory cortex contralaterally Does the brain first Touch = mechanoreceptors, have Ab nerve fibres, which have greater diameter and detected the heat or the thicker myelin than Ad fibres, while C fibres are not myelinated at all and have small surface first (2020) diameters Pain and heat = has Ad or C fibres DIAMETER: as diameter increases, nerve conduction velocity increases as total internal resistance decreases for current to flow down length of axon MYELINATION: prevents ion leakage across membrane, also increases the nerve conduction velocity Thus the nerve conduction speed for mechanoreceptors (touch) will be much faster than that of pain and heat receptors, thus the brain will detect the surface first. Eye RECEPTIVE FIELD = area in the retina that generates a response in the bipolar cells Describe the receptive when it is stimulated, is circular and consists of a centre and surround field of bipolar cell in the - Center contains photoreceptor that is directly connected to a (on or off) bipolar retina, how would a cells, while surround consists of photoreceptors connected to the centre bipolar cell expressing photoreceptor and the bipolar cell via horizontal cells AMPA/Kainate - Bipolar cells with AMPA/Kainate are hyperpolarized in light, and thus are receptors respond to a off-centre bipolar cells stroke of light in the - AMPA/Kainate is an ionotropic receptor, which mimics the [photoreceptor receptive field? response and it is proportional to the amount of glutamate released! Comparing rods and Rods Cones cones (2016) Photopigment Rhodopsin Opsin Sensitivity to All wavelength of Wavelength of red, wavelength visible light green & blue light Location All over retina (x fovea) Fovea, macula lutea Sensitivity to light High Low Colour Shades of grey (B/W) Coloured vision Type of sight Night Day Fovea has high Fovea is a depression in the exact centre of the retina with no ganglion or bipolar cell resolution (2020) layers, only with cones, making it the point of most distinct vision Accommodation (2017, 2011) Accommodation: ability of the eye to adjust the refractive power of the lens to bend light inwards into a point to be focused on light sensitive retina to achieve accurate images. Far vision: ciliary muscle relaxes, suspensory ligament taut, lens flattened, decreased extent of refraction of light Near vision: ciliary muscles contracts, suspensory ligament slackens, lens rounder, greater refraction of light Others: Bright light: CCRR circular muscles contract, radial muscles relax (iris) dark VV Diagram of cochlea (2015) Key processes underlying the 1. Sound waves travel down the ear canal and strikes the tympanic membrane transduction of sound 2. Pressure exerted on the tympanic membrane causes ossicles to vibrate, into a neural signal vibration of the malleus and incus causes stapes to exert force on the oval (2019) window 3. Pressure on the oval window induces movement in the basilar membrane Describe 2 organs of 4. Displacement of basilar membrane (with respect to the tectonic membrane) balance in the ear(2012) causes a depolarisation of hair cells 5. Depolarisation of outer hair cells changes their morphology to amplify the signals from inner hair cells 6. Depolarisation of inner hair cells induces L-glutamate release, which then evokes an action potential in the auditory (cochlea) nerve, inducing a neural signal 2 organs → (1) the utricle, made up of macula and saccule, and (2) a set of three semicircular canals Describe involvement of Sound waves cause an oscillatory movement in the basilar membrane which moves basilar membrane and the stereocilia back and forth (/deflection of stereocilia to move from side to side) hair cells of cochlea in - When basilar membrane is displaced upwards, the stereocilia is deflected, causing a causing alteration of AP depolarizing sensory receptor potential, thus increasing AP frequency generation in auditory - When basilar membrane is displaced downwards, the stereocilia is deflected in the nerve (2009) other direction, (closing the..) causing hyperpolarizing sensory receptor potential, decreases the frequency of action potential in the auditory afferent nerve WHEN: a very large sound is detected Attenuation reflex FUNCTION: prevents delicate sensory apparatus from potential damage (protection from prolonged loud sounds) HOW: muscles (tensor tympani and stapedius) contract reflexively in response to loud sounds, causing tympanic membrane to tighten and limit movement of ossicular chains, diminishing hearing sensitivity Classic GPCR Rhodopsin Stimulus Chemical Light Receptor activation G protein brings to GTP G protein brings to GTP Enzyme Activation Activation 2nd messenger Increase in 2nd messenger lvls Decrease in 2nd messenger lvls Ion channel increase/decrease conductance Decreases Na+ conductance BLOOD Concept tested What to cover Name the constituents The major constituents of plasma are plasma proteins, there are 3 groups of plasma of plasma and state proteins one function each 1. Albumin - most abundant, it contribute extensively to the colloid osmotic (2019) pressure, and non-specifically binds to many substances that are poorly soluble in plasma to be transported in the plasma (eg penicillin) 2. Globulin - there are 3 subclasses; alpha, beta and gamma a. Alpha and beta: binds highly specific poor water soluble substances for transportation in the plasma, involved in blood clotting and is an inactive precursor protein b. Gamma: immunoglobulins (antibodies) for defence mechanism 3. Fibrinogen - key factor in blood clotting Electrolytes (such as Na+, K+, Ca2+ and Cl-) Maintains membrane excitability and osmotic distribution of fluid between the ECF and ICF Briefly describe the 3 1. Neutrophils granulocytes found in a. Multilobed (up to 5) nuclei, inconspicuous cytoplasmic granules, blood and state the diameter of 10-12 micrometres major function of each b. Function: phagocytosis to remove pathogens and cell debris (2017) 2. Eosinophils a. Bilobed nucleus, red cytoplasmic granules, diameter of 10-14 micrometres b. Function: essential for protection from parasites such a roundworms, attracted to the chemicals released by the ingested parasite, then degranulate and release histamine to kill the parasite 3. Basophils a. Bilobed nucleus, dark blue staining, large granules, diameter of 8-10 micrometre b. Function: synthesis, storage and release of heparin and histamine, heparin speeds up the removal of fat particles from the blood, an anticoagulant, while histamine is important in allergic reactions Describe natural killer Natural killer cells = cytotoxic lymphocytes, and are part of the innate immune system cells and their main (not to be confused with cytotoxic T cells that are part of the adaptive immune system) functions ❖ Releases perforin, which forms pores in the cell membrane and causes apoptosis ❖ Plays a role in tumour rejection and cells that are infected by viruses ❖ Patients deficient in NK cells are susceptible to herpes virus infection ❖ NK cell activity is tightly regulated - prevent auto-reactivity, killing own cells- cytotoxic activity is controlled by surface expressed ‘activating receptors’ and ‘inhibitory receptors’ Mast cells = granulocytes, similar to basophils but have different lineages, and hence Describe the functions are different cells. of mast cells - Express Fc receptors, and bind to Fc of IgE. - Allergens bind to IgE on the mast cell surface and stimulate the release of histamine and heparin. - Histamine dilates venues increasing blood permeability causing edema (swelling), warmth, redness, attracts inflammatory cells and activates nerves (itching and pain) → attracts phagocytes and release of cytokines for pathogen removal and tissue repair. Describe the body’s 3 Protective surfaces: epithelial linings secrete antibacterial substances major mechanism of (lysozyme) and have an acidic pH that inhibits growth of pathogens, they are defence against a found in the skin and mucosal lining (GIT, respiratory, urinary, reproductive tract) pathogen + skin barrier? Innate immune system: they are cells, complement proteins and peptides in the blood, or tissue that beat trivial infections, the cells of the innate immune are neutrophils, eosinophils, basophils, macrophages, mast cells and natural killer cells (2013) Adaptive immune system: has cells with the ability to learn and adapt, allowing cells to generate a greater response to subsequent infections. T lymphocytes are responsible for cellular response and interact with APCs such as macrophages and dendritic cells. B lymphocytes are responsible for humoral responses and production of antibodies. T lymphocytes, B lymphocytes (2013) Briefly discuss the 1. First exposure to pathogen’s antigen either a natural exposure to virulent, antigenic means of acquiring long pathogen or non-virulent antigenic pathogen through vaccination term immunity (2019) 2. This leads to cellular response from T lymphocytes which interact with APCs (such Describe the means by as macrophages or dendritic cells) and they become activated which a body acquires 3. Activated T cells proliferate and differentiate into memory T cells which are long-lived long term immunity 4. (humoral response from B cell) B cells expresses the immunoglobulin receptor on from a pathogen (2015) surface membranes, and antigens bind to this receptor 5. B cells differentiates into memory cells to allow for quick attack of subsequent attacks of the same antigen. APC: Describe the steps in 1. Invading bacteria phagocytosed by dendritic cell antigen presentation 2. Endocytic vesicle containing bacterium fuses with lysosome, enzymatically and helper T cell breaks down bacteria proteins into antigenics peptides activation + activation 3. Each peptide binds to MHC that was newly synthesised within ER/GA of B cells by helper T 4. Antigen presented on cell surface, bound to MHC, cell is APC cells Helper T cell activation: 1. Helper T cell with helper T cell receptor specific to the antigen-MHC complex presented on the APC binds complementarily (using my H2 bio lol) 2. APC secretes interleukins, which activates the T cell 3. Activated T cell secretes cytokines which stimulate T cell to proliferate and expand B cell activation 1. TCR of helper T cell recognises the specific antigen (B cell is APC, so got antigen-MHC complex), and binds 2. Helper T cell secretes interleukins which stimulate B cell proliferation to produce clone of selected cells, activating it 3. Some cloned B cells differentiated into plasma cells, which secrete antibodies specific for the antigen, while a few differentiate into memory B cells Functions of the 4 types of T cells and their CYTOTOXIC – kill infected cells via lysis roles HELPER – key regulating cells of the specific immune response, (i) enhances the activity of cytotoxic T cells as well as phagocytic activity of macrophages, and (ii) stimulate the development of B cells into plasma cells SUPPRESSOR – secretes cytokines that suppress activity of B cells and other T cell types, inhibiting phagocytosis, controls autoimmunity to prevent self attack in diseases such as arthritis, MS, crohn’s disease, diabetes, asthma and others MEMORY – long lived activated T cells that remain for subsequent activation Describe the role of B lymphocytes in B cells can respond to either T independent or T dependent antigens. T independent adaptive immunity antigens can stimulate antibody production without T cell involvement while T (2020) dependent antigen requires helper T cells. Most B cells differentiate into plasma cells which produce antibodies that can combine with specific types of antigen that stimulate the activation of the plasma cell (cell-mediated) or dormant memory cells which allows for quick attack against the same antigen in future infections. Role of platelets Platelets are cell fragments that shed off the outer edges of megakaryocytes, and thrombopoietin (produced in liver) increases number of megakaryocytes to produce more platelets - Aids in hemostasis, formation the platelet plug Function of thrombopoietin (2012) Produced in the liver, increases the number of megakaryocytes in the bone marrow to produce more platelets. Haemopoiesis Required to make sure the numbers are relatively constant Derived from a single hematopoietic stem cell (haemocytoblast) which is only found in the bone marrow, may differentiate into one of the 5 progenitor cells, each progenitor gives rise either: erythrocytes, granulocytes, lymphocytes, monocytes or platelets (from mega) Normal life cycle of RBC 1. Erythrocytes are formed in the bone marrow 2. They circulate in the bloodstream for 120 days 3. Aged erythrocytes are phagocytized in the liver and spleen 4. Heme components of blood are recycled a. Iron recycled back into haemoglobin production b. Heme is converted into biliverdin, then bilirubin, which is secreted in bile from the liver 5. Membrane proteins and globin proteins are broken down into amino acids, some of which are used to make erythrocytes Structure and function of RBC (2016) / → NO NUCLEUS, ORGANELLES OR RIBOSOMES, can make room for Hb characteristic that make → BICONCAVE to increase surface area to volume ratio to allow for more efficient them ideally suitable for diffusion of oxygen across membrane the function → THIN to enable rapid diffusion of O2 by the binding of haemoglobin and CO2 in the form of bicarbonate by the facilitation of carbonic anhydrase → FLEXIBLE shape which allows them to squeeze through capillaries without Structure and function of rupturing in the process haemoglobin Structure Haemoglobin is made up of 4 polypeptide chains, 2 alpha and 2 beta subunits, all the chains have a heme group attached to it. Heme group has an iron ion which gives haemoglobin its red pigmentation, each haemoglobin has 4 iron ions, allowing 4 oxygen molecules to bind to it. Function Oxygen binds reversibly to the iron ion in the haemoglobin in the lungs and leaves Hb when in tissues. It also binds to CO2 in the form of bicarbonate, which process is facilitated by carbonic anhydrase. This allows the transport of CO2 out of the body and also acts as a buffer for the pH of the blood. (2012) Binds to oxygen and CO2 in the form of carbon, which is facilitate by carbonic Process of anhydrase, it transport oxygen to tissue and CO2 to lungs to be expelled erythropoiesis and an example to induce it An example to induce erythropoiesis is to go to higher altitudes when O2 levels low, (2010) reduced O2 to kidneys, stimulates the secretion of erythropoietin, which stimulate erythropoiesis 1) Pluripotent stem cells differentiate and give rise to myeloid stem cells 2) Myeloid stem cells are partially differentiate and give rise to erythroblasts 3) Erythroblasts are nucleated, and are committed to becoming mature erythrocytes, they start to extrude their nucleus and organelles to make room for haemoglobin, becoming immature RBC that contains organelles remnants, reticulocytes 4) Reticulocytes then expels these remnant organelles to give rise to erythrocytes :)))) (2012) function of ERYTHROPOIETIN Produced in the kidney, acts on derivatives of undifferentiated stem cells (reticulocytes), stimulates their proliferation & maturation into mature erythrocytes Describe the role thrombin plays in haemostasis (2015, 2018) Thrombin is a component of the clotting cascade and plays multiple roles in haemostasis. 1 - it stimulates the conversion of fibrinogen to fibrin (a loose meshwork) that adheres to the site of the damaged vessel 2 - it actives factor XIII which forms chemical linkages between adjacent fibrin strands to strengthen and stabilise the clot meshwork 3 - it enhances the activation of more prothrombin to thrombin through a positive feedback loop 4 - it enhances/stimulate platelet aggregation 5 - which through positive feedback loop, the aggregated platelets secretes platelet factor 3 (PF3), which stimulates the clotting cascade and hence activating more thrombin Discuss the different The clotting cascade can be triggered by an intrinsic and extrinsic pathway. pathways of clotting INTRINSIC PATHWAY involves 7 steps and is set off when factor XII (Hageman’s blood (2010) factor) is activated by coming into contact with exposed collagen or a foreign surface. EXTRINSIC PATHWAY involves 4 steps and requires contact with tissue factors external to the blood. Tissue thromboplastin (F3) is released from traumatised tissue, which activates factor X, bypassing all preceding steps in the intrinsic pathway In both pathways, factor X activates prothrombin to thrombin which causes the conversion of fibrinogen to fibrin, a loose meshwork. Thrombin also activates Factor XIII to form strong chemical linkages between the adjacent fibres of the loose meshwork to strengthen and stabilise it, hence forming a clot. Function of the - Return excessive interstitial fluid to blood. This is because capillary filtration lymphatic system exceeds reabsorption and a lot of plasma volume is left in interstitial fluid everyday. Fluid enter lymph vessels, and is pumped to the lymph nodes and then returned to circulating plasma near the right atrium - Also plays a role in defence against disease by producing, storing and distributing lymphocytes - Transports lipids and lipid soluble vitamins that are too large to enter blood capillaries in the digestive system but can enter the lymphatic system ** Describe Erythroblastosis fetalis (aka Rh disease/haemolytic disease of newborn) erythroblastosis fetalis - Presence of antigen D on the RBC means the person is Rh+, no antigen D and how it can be means the person is Rh- prevented (2022 - EF occurs when RH- mother carries a Rh+ baby. Rh- person does not normally sample, 2021) carry antibodies to Rh+ antigen unless exposed to it - May occur when Rh- mother and Rh+ father have a Rh+ baby, mixing of baby and maternal blood at birth, so the mother will start producing antibodies to the Rh+ antigen on baby’s RBC. there is no danger to the 1st child. - Haemolysis of RBCs of fetus (2nd Rh+ child) can occur, and this might result in anaemia or worse Prevention: Rho(D) immune globulin (RhoGAM) - Treatment for Rh disease, contain antibodies specific for Rh+ antigen (anti-D antibodies) - Prophylactic treatment - Removes Rh+ RBCs from maternal blood before her immune system become sensitised to it - Injected within 72 hours after birth of the positive baby Name one disorder i) low number of basophils = BASOPENIA, one disorder associated with basopenia is associated with low autoimmune urticaria, it usually presents with hives and causes itching numbers of (2018) ii) low number of eosinophils = EOSINOPENIA, one disorder associated is Cushing’s disease, which is the excessive production of cortisol. It usually presents with fatty deposits such as moon face or buffalo lump, particularly at mid-section or upper back. iii) low number of neutrophils = NEUTROPENIA, can be associated with leukaemia and anaemia Name 5 types of 1. Nutritional: lack of a factor required in erythropoiesis eg iron deficiency and anaemia and state one hence inability to produce enough Hb (smaller, fewer RBC less Hb, cause of each (2017) hypochromic) 2. Renal: impaired erythropoietin synthesis in the kidneys due to renal disease 3. Aplastic: bone marrow does not produce enough RBCs even though there are essential components, can be due to cancer, chemotherapy or radiation 4. Haemorrhagic: loss of a lot of blood 5. Haemolytic: rupturing of RBCs, could be due to sickle cell or malaria invading RBCs 6. Pernicious: inability to absorb vit B12 in the GI tract because of a defective intrinsic factor (B12 required for DNA production, proliferation is impaired, macrocytic, odd shaped, fewer) Talk about the 2 types of Polycythaemia = presented as excess circulating erythrocytes, elevated hematocrit polycythaemia and its causes PRIMARY polycythemia: tumour like condition of bone marrow Erythropoiesis proceeds at an excessive uncontrolled rate; hematocrit may be as high as 70% (normal of 42%) Excessive RBC increases blood’s viscosity which reduces oxygen delivery to tissues and increases total peripheral resistance which may elevate blood pressure SECONDARY polycythemia (or relative polycythemia): occurs normally in people living at high altitudes, where less O2 is available. Body loses fluid but not erythrocytes to raise hematocrit (through sweating or profuse diarrhoea) ? ENDOCRINE Concept tested What to cover Difference between NT: hormones and - Can only travel along existing neural tracts neurotransmitters (2016) - FAST and PRECISE response - Digital, ALL OR NOTHING events, that are rapid onset and offset HORMONES: - Travels in the circulatory system - LONG duration responses - Analog, GRADED events that can take second, minutes and hours Feedback control of hormone secretion = where the target gland hormone inhibits its secretion via negative feedback (2020) - Accomplished by the target gland hormone, either acting directly on the pituitary itself or on the release of hypothalamic hormones + target gland hormone also suppresses secretion of tropic hormone that is driving its secretion - Eg TSH → THs, then the THs have a -ve feedback on the AP to inhibit TSH Hypothalamic - = a capillary to capillary connection from the hypothalamus to the anterior pituitary hypophyseal portal VASCULAR arrangement whereby venous blood flows directly from one capillary bed system (sample 2021, through the connecting vessels to another capillary bed 2022) HYPOPHYSIOTROPIC hormones produced by neurosecretory neurons in the hypothalamus enters the hypothalamic capillaries, hypothalamic capillaries rejoin to form the HHP system (vascular link to AP) Portal system branches into capillaries of the AP Hypophysiotropic hormones leave the blood along the anterior pituitary capillaries, controls the release of anterior pituitary hormones When stimulated by the appropriate hypothalamic release hormone, the anterior pituitary secretes a given hormone into these capillaries The AP capillaries rejoin to form a vein, through which the anterior pituitary hormones leave for ultimate distribution throughout the body by the systemic circulation ADH When the ECF is hypotonic, ADH Draw a diagram to secreted illustrate the action of 1. Blood-bourne vasopressin ADH in the distal tubule binds onto the V2 receptor (2010, 2018) sites on the basolateral membrane of the principal cell of the distal tubule 2. Binding of ADH activates the cAMP 2nd messenger pathway in the cell 3. cAMP activation increases the permeability of luminal membrane to water by facilitating insertion of aquaporins (AQP-2) via exocytosis. Without ADH, the luminal membrane is impermeable to water. 4. Water enters the tubular cells across the luminal membrane via the AQPs 5. Water leaves via other aquaporins (3 / 4) on the basolateral membrane (which are permanently positioned on the membrane) into the blood, thus reabsorption occurs. When ADH concentration decreases, cAMP decreases, AQP-2 retrieved through endocytosis Growth hormone Overall metabolic effect = effect of GH is to mobilise fat stores as major energy stores, Metabolic effect (not while conserving glucose for glucose dependent tissues (eg the brain) related to growth) (2015) 1. Increased fat breakdown, increased free fatty acids in the blood 2. Decreased muscle uptake of glucose, increased blood glucose levels 3. Increased tissue amino acid uptake (promotes protein synthesis) Thyroid 1. Tyrosine-containing thyroglobulin (Tg) is synthesised within the follicular cells by How is the thyroid the ER/GA, and then released into the colloid by exocytosis hormone secreted 2. Iodide carried from the bloodstream via secondary active transport via (sample, 2021) symporters on the basolateral membrane of the follicular cells to the colloid 3. In the cell, iodide is oxidised into its active form by thyroperoxidase (TPO) on the luminal membrane 4. Activated iodide transported via luminal channel into the colloid 5. In the colloid, TPO catalyses the attachment of the activated iodide onto the tyrosine in the Tg, forming monoiodotyrosine (MIT) a. Attachment of 2 iodide residues to tyrosine forms DIT b. Coupling of one MIT wit one DIT forms T3 c. Coupling of two DIT yields T4 6. Upon appropriate stimulation, the thyroid follicular engulf a portion of the colloid containing the Tg by phagocytosis 7. Lysosome fuse with the engulfed vesicle, split the iodinated products from Tg 8. T3 and T4 diffuses into the blood 9. MIT and DIT are deiodinated, freed iodide recycled for synthesising more hormones THYROID STIMULATING HORMONE TSH (released from the anterior pituitary gland) Regulation (2020) stimulates the thyroid gland to secrete the thyroid hormones T3 and T4. When there is an excess of THYROID HORMONE being produced, thyroid hormone will have a negative feedback on the anterior pituitary, to inhibit the secretion of TSH! Thyroid hormones Functions of the thyroid 1. Main determinant for basal metabolic rate, which influences the synthesis and hormones and degradation of carbohydrates, fats and proteins hyperthyroidism (2020) 2. Increases target cell responsiveness to catecholamines (NE and E) 3. Increases heart rate and force of heart contraction 4. Essential for normal growth 5. Plays a crucial role in development of nervous system Hyper → excessive secretion of thyroid hormone, can be due to Grave’s which is an autoimmune disease where the body erroneously makes thyroid stimulating immunoglobulins (TSI), which is an antibody whose target is the TSH receptor of the thyroid cells. TSI stimulates both secretion of thyroid hormone and growth of thyroid gland in the same manner TSH has on the thyroid. BUT TSI is not affected by the negative feedback loop inhibition by thyroid hormone, so thyroid secretion and growth continues unchecked!!!!! (**secondary cause if due to excess thyrotropin releasing hormone, TSH or hypersecreting thyroid) Insulin secretion 1. Glucose enters the beta cells of the pancreas via facilitated diffusion through (sample) GLUT-2 transporter protein 2. Within the cell, glucose is phosphorylated into glucose-6-phosphate, and then Explain the stimulation phosphorylated further of insulin secretion by 3. Phosphorylation of G6P releases ATP glucose via 4. ATP acts on ATP-sensitive K+ channels, closing it excitation-secretion 5. Exit of K+ out of the cell is prevented, membrane depolarised coupling 6. Opens the voltage-gated Ca2+ channels, Ca2+ enters the beta cells 7. Triggers the exocytosis of vesicles containing insulin to fuse with the cell membrane, insulin is secreted out of the cell Describe in brief the Generalised stress response: mechanism behind Increased epinephrine secretion from chromaffin cells generalised stress Increased CRH-ACTH-Cortisol, mobilising fats, carbohydrates and metabolic response resources Decreased insulin, increased glucagon (blood glucose and FAs increase) Increased RAAS and ADH secretion, blood volume and bp regulation Chronic stress: Causes heart disease, atherosclerosis, hypertension and immunosuppression Prolonged CRH can cause depression and anxiety Stress (primary stimulus) → sympathetic input directly to the gland State the main Adrenal cortex: aldosterone, cortisol, DHEA (dehydroepiandrosterone) hormones secreted by Adrenal medulla: epinephrine and norepinephrine adrenal cortex and (Epi) dilates respiratory airways, reducing resistance encountered by air moving in and medulla and write one out of lungs, (both?) maintenance of arterial blood pressure, increased blood glucose, function of each increased fat metabolism (increase in FA in blood) - mobilisation of sources Maintaining Ca and Ca and phosphate levels are maintained by three enzymes; parathyroid hormone, phosphate (sample calcitonin and vitamin D. 2022, 2017, 2019) - Parathyroid hormone (PTH) is secreted from the principal (chief) cells of the parathyroid gland in response to low blood Ca2+, PTH increases serum Ca2+ Parathyroid hormone levels. It induces a FAST efflux of Ca2+ into the plasma from the small liable function (2014) pool of Ca2+ in the bone fluid, and SLOW transfer of Ca2+ and phosphate into the plasma from a stable pool of bone minerals in the bone itself + stimulates kidney tubule reabsorption of Ca2+ + increase Ca2+ absorption from small interesting via activated Vit D - Vit D is supplemented from the diet, cholesterol derivative when exposed to the sun, then activated in the liver and then the kidney (by addition of 2 hydroxyl groups) aids in Ca2+ and phosphate absorption in the GI tract + increases renal absorption of Ca + regulates activity of osteoblast and osteoclasts - Calcitonin released from the C cells in the thyroid when there is a high plasma Ca2+ concentration, high concentrations of calcitonin, acts antagonistically to PTH, acts to lower plasma Ca and phosphate levels ;decrease the Ca2+ movement from the bone fluid to the plasma in the short term, and in the long term, decrease bone resorption by inhibiting osteoclasts activity via a cAMP pathways + lowering plasma Ca2+ and phosphate levels + stimulates secretion of Ca2+ from kidney, increases production of inactivated Vit D (thus delaying Ca2+ absorption from the intestine) Physiological: muscle contraction, structural integrity of bones and teeth, blood clotting, Physiological roles of enzyme regulation, membrane stability calcium and functions Functions of free ECF of free ECF Ca2+ 1. Prevent aberrant neuromuscular excitability Fall in free Ca = overexcitability of nerves and muscles (increased Na perm) Rise in free Ca = depresses neuromuscular excitability (decreased Na perm) 2. Excitation-contraction coupling: in smooth and cardiac muscle cells (^) increased Ca, depresses, decreases likelihood of contraction 3. Stimulus secretion coupling: entry of Ca into secretory cells in response to appropriate stimulation triggers release of secretory products by exocytosis 4. Excitation secretion coupling: pancreatic B cells, calcium leads to insulin secretion 5. Maintenance of tight junctions between cells: Ca forms intercellular cement that hold particular tight unions together 6. Clotting of blood: acts as cofactor in several steps of the cascade ? OSTEOBLASTS = secretes extracellular organic matrix within which calcium phosphate precipitates OSTEOCYTES = retired osteoblasts imprisoned within the bony wall that they have deposited OSTEOCLASTS = resorption of bone, derived from macrophages Cushing’s disease FROM: excessive production of glucocorticoids due to an adrenocorticotropic secreting (2019) tumour in the pituitary (adenoma) KEY FEATURES: weight gain and fatty tissue deposits, esp around the mid and upper back, in face (moonface) and between shoulders (buffalo hump) + pink/purple stretch marks on skin of abdomen, thighs, breasts or arms, thinning fragile skin that bruises easily TREATMENT: treated by anti-glucocorticoids medication, surgery to remove the tumour or surgical adrenalectomy Diabetes Type I: symptoms develop rapidly, childhood onset, comprises 10-20% of diabetics Cause: loss of β cell function, insulin secretion none/low Treatment: Insulin injections Type II: symptoms develop slowly, adulthood onset, comprises 80-90% of diabetics Cause: Insulin insensitivity, insulin secretion normal/high Treatment: diet/exercise, oral drugs Effects of severe diabetes 1. Excessive eating: cells starved of carbs, hypothalamic centre leads to excessive eating 2. Dehydration and thirst: low glucose uptake, blood glucose rises, glucose appears in urine, increases urinary volume, dehydration and thirst + (ADH) failure of ADH secretion, or reduced sensitivity to ADH = more urine 3. Coma: cells unable to use glucose increases, lipolysis generate fatty acids and ketoacids, keto acids lower blood pH, decreased brain O2, coma 4. Brain cells are glucose obligate cells ; low glucose, the brain stops working, coma and respiratory paralysis Name 6 anterior pituitary hormones and state 1 function of each. (2017/2018) HORMONES Produced from ACTION Growth hormone Anterior pituitary Regulates growth in the body (controlled by Overall effect: mobilise fat stores as a major energy substrate while hypothalamic conserving glucose for glucose dependent tissues hormones) 1. Decreased glucose uptake by muscle, increased gluc level in blood 2. Promotes proteins synthesis, increase a/a uptake 3. Fatty acid breakdown, increased free fatty acid levels in blood 4. Growth (stimulates IGF somatomedins production in liver) GH inhibits the hypothalamic GHRH secretion and stimulates somatostatin GHIH release [short loop] Thyroid stimulating Stimulates thyroid gland to produce T3 and T4 hormones hormone Adrenocorticotropic Regulates the secretion of cortisol to increase blood glucose levels (acts hormone on the adrenal cortex) Prolactin Stimulates lactation FSH Stimulates production of gametes LH Controls sex hormone secretion Oxytocin Posterior pituitary 1. Stimulates contraction of uterine smooth muscle, push baby out (made in hypo, 2. Stimulates smooth muscle contraction (for milk ejection) released from 3. Influence maternal behaviour (bonding, attachment), brain function? PP) ADH 1. Increasing permeability to water, enhancing water retention in the kidney during urine formation (antidiuretic - less pee) 2. Contraction of arteriolar smooth muscle Somatostatins From delta cells GHIH = growth hormone inhibiting hormone in pancreas 1. Inhibits GH and TSH secretion from the anterior pituitary Hypothalamus 2. Assists glycogen breakdown of glucagon (supports glucagon) Somatomedins Liver Produced in response to GH stimulation IGF-1 1. Promotes the growth of bone and soft tissue by hyperplasia (cell division/proliferation) 2. Stimulates protein synthesis, increased blood a/a levels, hypertrophy (??? cell growth), inhibiting apoptosis IGF-1 inhibits GH secretion by anterior pituitary, inhibiting GHRH secreting cells, stimulating GHIH (somatostatin)-secreting cells [long loop] T3, T4 Thyroid gland 1. Main determinant of basal metabolic rate 2. Influences synthesis & degradation (turnover) of carbs, protein, fat 3. Increases large cell responsiveness to catecholamines (wts???) 4. Increases heart rate and force of contraction 5. Essential for normal growth (action of GH only fully manifest when enough TH present) & plays a crucial role in development of nervous system T3 and T4 inhibits anterior pituitary (TSH) secretion [negative feedback, short loop] Aldosterone Adrenal cortex Acts on the distal and collecting tubules in the kidney (zona 1. Promotes Na+ retention, and excretion of K+ and H+ glomerulosa) 2. ^thus induces retention of water, expanding ECF volume Cortisol Adrenal cortex CRH → ACTH → cortisol; overall effect to increase blood glucose at (zona fasciculata) expense of protein and fat stores 1. Resisting stress 2. Increase blood glucose, increase blood FAs 3. Controls water and electrolyte balance 4. Anti-inflammatory Cortisol inhibits hypothalamus from releasing corticotropin-releasing hormone (CRH) [long loop] and adrenocorticotropin hormone (ACTH) from the anterior pituitary gland [long loop] DHEA Adrenal cortex 1. In males, overpowered by testosterone (zona reticularis) 2. In females, growth of pubic and axillary hair, enhancement of pubertal growth spurt and development and maintenance of female sex drive Epinephrine Adrenal medulla Primary stimulus: activation of the SNS by stress, triggering release Norepinephrine Chromaffin cells “Fight or flight” response! 1. Maintenance of arterial blood pressure 2. Increased blood glucose 3. Increased fatty acids in blood (increased fat metabolism) 4. (Epi) dilates respiratory airways, reduce resistance encountered by air moving in and out of lungs Insulin Pancreatic B Conversion of glucose into glycogen, FAs into triglycerides, and amino cells acids into proteins (ANABOLIC) Glucagon Pancreatic A Antagonist to insulin; conversion of glycogen into glucose, triglycerides cells into FAs, and proteins into amino acids (CATABOLIC) Parathyroid Parathyroid gland 4 functions = overall effect to increase the Ca2+ in the ECF hormone 1. FAST efflux of Ca2+ from bone fluid 2. SLOW transport of Ca2+ & phosphate from bone mineral 3. Increase kidney tubule reabsorption of Ca2+ 4. Increase Ca2+ absorption from the small intestine (via Vit D) Activates vit D, increases efficiency of uptake of ingested Ca2+ Calcitonin C cells in the 1 short term, 3 long term = antagonist of PTH, decrease Ca2+ thyroid gland 1. (S) Decreases Ca2+ movement in 1^ bone fluid 2. (L) Decreases bone resorption, inhibiting osteoclasts via cAMP pathway 2^, lowering plasma Ca and phosphate 3. (L) Stimulates Ca2+ secretion from kidney 3^ 4. (L) Increase production of inactive vit D (delaying 4^) Vitamin D From diet then to 3 functions = works with PTH to increase the Ca2+ levels liver turn to 1. GI tract absorption of Ca and phosphate (see diseases) kidney 2. Increase kidney tubule reabsorption of Ca2+ 3. Regulate the activity of osteoblasts and osteoclasts DISEASES DISEASE WHAT IT IS SYMPTOMS TREATMENT Addison’s Low corticol (cortisol and aldosterone) Hypoglycemia, decreased Steroid replacement disease 1 - damaged to the adrenal gland (resulting liver glucagon, fatigue, therapy; from TB or autoimmunity) anorexia, weight loss, fludrocortisone 2 - low ACTH release from AP dizziness, hypotension Cushing’s High glucocorticoid (cortisol) Elevated bp (hypertension), Removing the disease Excess cortisol caused by ACTH secreting obesity, muscle wasting, tumour TUMOUR in the anterior pituitary *moonface, buffalo hump, Anti-glucocorticoids osteoporosis, poor wound healing, cataracts + psych Conn’s High mineralocorticoid (aldosterone) Sodium and water Unilateral syndrome Excess aldosterone caused by TUMOUR retention, increase in ECF, adrenalectomy (1) or excessive RAA action in kidney hypertension Aldosterone disease, liver cirrhosis & heart failure (2) antagonist (spironolactone) Hereditary Low GHRH dwarf Laron dwarf Defective GH receptor African pygmy Defective IGF-1 receptor Acromegaly Excess GH caused by tumour cells Thickening of bones, Taking meds (benign tumours - adenomas) of the coarsened facial features, (reduce GH anterior pituitary gland, children soft tissue swelling, heart secretion) e.g. (gigantism) adults/after adolescence failure, vision loss somatostatins stop (acromegaly) GH production (pituitary) Gigantism Goiter When thyroid gland is over stimulated Enlargement of thyroid (usu when there is high TSH/TRH) gland Cretinism = hypothyroidism in infants Myxedema = hypothyroidism in adults Hashimoto’s Hypothyroidism Autoimmune, autoantibodies destroy thyroid follicular cells (thyroid problem, primary hypothyroidism) High TSH, low T3, T4 Grave’s Hyperthyroidism High metabolic rate, Beta blockers, Autoimmune, TSH mimicked by protruding eyes, anti-thyroid autoantibodies (thyroid stimulating hyperactivity, insomnia, medications, immunoglobulin TSI) heat sensitivity, weight loss radioactive iodine Low TSH, high T3, T4 treatment Type I Loss of B cell function, insulin secretion Insulin injections non/low Type II Insulin insensitivity, insulin secretion diet/exercise, oral high/normal drugs Rickets Vitamin deficiency, impaired intestinal Ca2+ salts not there for (children) absorption of Ca2+, PTH maintains plasma deposition, bone becomes Osteomalacia calcium levels at expense of bone, bone soft and deformed, bowing (adult) matrix not properly mineralised under pressure of weight bearing 2 Hyper- PTH hypersecretion - muscle weakness, parathyroidism Hypersecreting tumour in one of the PTH neurological disorders, glands, characterised by hypercalcemia decreased alertness, poor and hypophosphatemia memory & depression - bone thinning, causing skeletal deformities, and increased incidence of fractures - increased incidence of calcium containing kidney stones - peptic ulcers, nausea and constipation Hypo- PTH hyposecretion Increased neuromuscular parathyroidism Autoimmune attack of the PT gland (rare), excitability - leading to hypocalcemia and muscle cramps, twitches hyperphosphatemia from spontaneous activity in motor nerves, tingling pins and needles sensation from spontaneous activity in sensory neurons DEFINITIONS Neuro membrane potential separation of opposite charges across a membrane graded potential local changes in membrane potential that occur in varying degrees of magnitude, at specialised regions of excitable cell membranes action potential brief, rapid, large changes in membrane potential during which the potential reverses and the inside of the cell becomes more positive than the outside saltatory conduction action potential jumping from node to node (NOR) in myelinated axons, increasing rate of AP propagation vs contiguous conduction Refractory period Where new APs cannot be initiated by normal events in the region (absolute) V-gated Na channels cannot open again in response to another depolarising triggering event, no matter how strong (relative) 2nd AP can be produced by triggering event that this is considerably stronger than usual Long term Synaptic transmission is plastic, ie, can be down or up regulated, which is evoked by an potentiation LTP increased or decreased use of synapse Sliding filament cross bridges form and break; actin slides over the myosin filaments and the muscle theory shortens. Motor unit *** 1 Motor neuron + all the skeletal muscle fibres innervated by that motor neuron’s axonal terminals Fatigue Inability to maintain muscle recruitment at a certain level, usually during sustained contraction Sensory Stimulus Change detected in the body Sensory Decline in receptor potential over time despite continued stimulation (divided into tonic adaptation and phasic receptors) Transduction ** Process of converting energy into electrical signals via a receptor/generator potential, which triggers an AP (if it is large enough to reach threshold) Sensory system Sensory receptor + axonal pathways + target ares in the brain involved in sensory perception Sensory Conversion of physical stimulus (energy) for example mechanical…, into electrical transduction signals (receptor potential) Myelin Membrane component of glial cells that surround and insulate consecutive axon segments in PNS (Schwann cells) and CNS (oligodendrocytes) Nodes of ranvier Myelin-free gaps between segments containing a (high concentration of) voltage-gated Na channels, provides a 50x increase in conduction velocity Receptive field Region a space in which when stimulates/presence of stimulus will alter the firing of that (general) neuron (piece of skin, retina, tongue) Somatosensory Neural sense concerned with sensations from the body, divisions are cutaneous, system visceral and proprioception Dermatome The area of the skin innervated left and right by the spinal nerves belonging to a specific spinal segment Pain Unpleasant sensory/emotional experience due to actual/potential tissue damage Nociception Processing of information about damaging stimuli by the nervous system up to the point where perception occur Proprioception Sense of the body’s position in space Lateral inhibition Where the fibres from neighbouring receptive fields inhibit on another, to enhance the contrast between wanted and unwanted information by blocking weaker inputs Receptive field The area of retina where a stimulus will evoke a response in the bipolar cell (eye) Horizontal and Local interneuron that modulate transmission to bipolar and ganglion cells amacrine cells Photo- Process of converting light energy/stimuli into its electrical signals (membrane potential transduction changes) Sensory The decline of receptor potential over time in spite of continued stimulation – can be adaptation Blood Endocrine 2022 questions Thrombins role in the clotting cascade (or the process of 4 types of dwarfism and briefly describe them OR Addison’s disease, treatment, symptoms Lever action of the arm or the gamma-motor neuron thingy Role of PDE in phototransduction or how the endolymph aids w the auditory thingy Saltatory conduction, basis and its advantages or AMPA sth work in progress

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