complete-summary-notes-for-hubs1416.pdf

lOMoARcPSD|23789778 Complete summary notes for HUBS1416 Advanced Human Bioscience (University of Newcastle (Australia)) Studocu is not sponsored or endorsed by any college or university Downloaded by Poppy Donchi (shoshana...

lOMoARcPSD|23789778 Complete summary notes for HUBS1416 Advanced Human Bioscience (University of Newcastle (Australia)) Studocu is not sponsored or endorsed by any college or university Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 Topic 1: Introduction to the Nervous System ! Name the parts of a generalised neuron & indicate the input, output and integration areas of the neuron. " Neurons are the functional cell of the nervous system that transmit electrochemical messages called nerve impulses or action potentials to other neurons and effectors (muscles or glands). Parts of a neuron: " Cell body (or soma): contains relatively large nucleus with a prominent nucleolus and produces proteins needed for other parts of the neuron. Cluster of cell bodies = ganglia. " Dendrites: [INPUT] highly branched ‘finger-like’ projections that receive information from other neurons. " Axons: [INTEGRATION] long nerve fibres that are capable of propagating electrical impulses known as action potential through them from cell body to axon terminal (*Electrical impulses rarely travel the other way). Cluster of neuron axons = nerves " Axon terminal: [OUTPUT] nerve endings that make synaptic contacts with other neurons and effector cells, they also contain various kinds of neurotransmitters (chemicals which convey the message across the synaptic space). " Myelin sheath: the insulating cover of axons which increases the speed at which electrical impulses travel along the neuron (*Not all neurons have a myelin sheath, only the ones that need fast electrical impulses). " A single neuron integrates it many inputs (inhibitory or excitatory) to produce a single output response (action potential or nerve impulse). o This allows: large amounts of info to be processed very quickly and acted upon. ! List the roles of glial cells in the nervous Ependymal system cells " The nervous system also contains specialised Glial cells which protect and support neurons. There are four types of neuroglia: " Astrocytes: o Structural support Neurons o Formation of scar tissue Microglial o Transport of substances between cell Capillary blood vessels and neurons Astrocyte o Communication with one another and with neurons Oligodendrocyte 1|Page s Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 o Mop up excess ions and neurotransmitters o Induce synapse formation. " Oligodendrocytes: o Form myelin sheaths in the brain and spinal cord (e.g. multiple sclerosis = myelin sheath deteriorates and signals slower) o Produce nerve growth factors " Microglia: o Structural support o Phagocytosis (immune protection as normal body immune cells don’t get into the CNS). " Ependymal cells: o Form a porous layer through which substances diffuse between the interstitial fluid of the brain and spinal cord and the cerebrospinal fluid. ! Explain in broad terms, what a membrane potential is, and what is required for it to exist. " All cells have a membrane potential, which is a difference in charge between the inside and outside of cells. " Only nerve cells and muscle cells can rapidly change their membrane potential as a means of creating a signal. This means these are excitable cells. " In rest state the inside of nerve cells are negative in respect to the outside of cells. " The voltage arises from differences in concentration of the electrolyte ions K+ and Na+. " Specific sodium channels and potassium channels are intrinsic to the membrane and selectively close and open to allow the passage of these ions across the membrane. " At rest, sodium channels are mostly closed and potassium channels open, so potassium moves down the concentration gradient (out of the cell), making is less negative to the outside. " This is known as resting membrane potential. " The concentration gradient is maintained by active transport (using ATP) of sodium ions out of cell and potassium ions in. " Known as the sodium-potassium pump. ! Describe how depolarisation and repolarisation are achieved in a neurone. " Depolarisation is what allows neurons to signal, which is the rapid reversal of the membrane potential from its rest state. " Thus, where the sodium channels are open allowing sodium ions into the cell making it positive to the outside. " After the signal, repolarisation occurs, where sodium channels close and potassium channels open allowing potassium to move out of cell and stop sodium moving into cell, creating a resting membrane potential again (negative inside). " A “wave” of depolarisation and repolarisation moves rapidly along the axon Sodium channels of neurones and more sodium channels open and close. " This process is known as nerve impulses. 2|Page Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 " This electrical communication converts to chemical communication at the axon terminal where the arrival of the action potential triggers the release of a neurotransmitter into the synapse. " This neurotransmitter diffuses across the synapse, binds to receptors on the other neuron and activating them and creating another action potential (message) which will travel down the axon. " The message is then terminated as the neurotransmitter is deactivated by being transported back to the axon terminal. ! Explain briefly why myelin increases the rate of conduction of axons. " In an unmyelinated axon, the action potential travels along rapidly, but the sodium channels have to be opened all the way along to keep the action potential going. This channel opening takes time. " Myelin creates a vacuum-like tunnel for the action potential to swiftly travel through before reaching a sodium channel that is further apart from the previous channel with the addition of myelin. ! Describe the following divisions of the nervous system & their relationships: Central & peripheral, Somatic & autonomic, Sensory & motor. The nervous system is divided into two parts: " Central Nervous System (CNS): o The CNS consists of two parts: # Brain (external grey matter = cell bodies with internal white matter = axons) # Spinal cord (external white matter = axons with internal grey matter = cell bodies) " Peripheral Nervous System (PNS): o The PNS consists of two parts: # Spinal nerves (31 pairs of nerves, each one emerging from different level of the spinal cord and supplying different segments of the body. Spinal nerves lead into peripheral nerves). # Cranial nerves (12 pairs of nerves, each emerge from different position in the brain and supplying different structure or group of structures). o The PNS is divided into two main parts: # Somatic nervous system (SNS): controls skeletal muscle, joints, tendons and skin: things we voluntarily control. # Autonomic nervous system (ANS): control our autonomic (involuntary) activities via glands and organs. This ANS is divided into three parts: Sympathetic (‘fight or flight’): controls short-lived behaviour E.g. increased HR, respiration rate, adrenalin released, slows down or turns off non-essential processes such as digestion & immune response to conserve energy in case needed. Parasympathetic (‘rest and digest’): maintains stable body functioning in normal conditions. Enteric Nervous system: The enteric nervous system is a meshwork of nerve fibres that innervate the viscera (gastrointestinal tract, pancreas, gall bladder). 3|Page Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 o The NS can be further divided into parts based on function: # Motor: efferent – responses going out from NS to environment through: Somatic motor functions: Movement of skeletal muscles (e.g. diaphragm, larynx) Facial muscles Autonomic motor functions: Movement of smooth muscles (e.g. blood vessels, airways, intestines). Gland activity # Sensory: afferent – stimuli coming in to NS from environment through: Somatic sensory functions: Senses i.e. touch, taste, smell, hearing, vision and balance (equilibrium in middle ear) Joint positions and muscle length (stretch contraction). Autonomic sensory functions: Chemoreceptors (samples blood for O2 & CO2) Stretch receptors (in hollow structures e.g. gut, bladder, uterus to check if full or empty). Baroreceptors (tests how stretched vessels are = monitors BP). ! Describe the components of a reflex arc, using a simple reflex as an example. 1. Stimuli from environment 2. Sensory receptors detect change 3. Change relayed to Central integrator (CNS) via sensory (effect) neurons 4. Action potential is transferred to motor (afferent) neuron through interneuron 5. Effectors then respond to stimuli Example: Stretch reflex (somatic) 1. Muscle is stretched by hammer tapping tendon in knee 2. This stretching is detected by the sensory skeletal muscle in leg 3. Action potentials travel along the sensory neuron into the spinal cord 4. Sensory neuron synapses with a motor neuron in the grey matter of the spinal cord 5. Motor neuron to muscle generates action potentials which cause the muscle to contract and the leg kicks as a response to tapping. 4|Page Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 ! Explain how reflex testing can be used diagnostically. ! Explain, in simple terms, why a simple reflex response can provide information about the functioning of both peripheral and central neurons. " Testing reflex can indicate whether there is damage to the CNS or PNS. " For example with the stretch reflex (knee jerk response) if there is no response to the knee tap, it indicates nerve damage that needs to be dealt with but if there are continual jerks after the tap can indicate cerebellar disease. " Therefore testing reflexes can indicate what the problem is and where the affected part is located through observing the patient’s response. ! Explain why some reflexes are present in infancy and disappear as we mature, while some reflexes are absent in infancy, and appear as we mature. " We are born with some reflexes to help us survive when we are young but as we develop more complex reflexes override existing ones from infancy to further benefit us in our environment. " It is abnormal for adults to still have the reflexes seen in infants. This can be identified through reflex testing. " Examples of primitive somatic reflexes: o The Moro reflex: startled look and arms spread apart when head is dropped lightly o The Babinski (plantar withdrawal) reflex: toes fan out when sole of foot is stroked o The Stepping reflex: stepping motions when sole of foot touches hard surfaces o The Rooting reflex: infant will move head towards side of cheek stroking and make suckling motions. o The grasping reflex: hand will close when you place finger in open palm ! Apply the information learnt this week to clinical problems on the nervous system. " Stroke: affects the body’s ability to recognise joint and limb position often because neurons are affected or can indicate a problem with sensory function. " A positive result for any primitive reflexes after about 2 years old is indicative of a problem. " Herniated disk = squashed spinal cord = weaker reflex (causes pin & needles) " Inflammatory lesions in white matter disrupt random signals which can cause random and unrelated symptoms. 5|Page Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 Topic 2: The peripheral nervous system ! Name and briefly describe the function of each of the 12 cranial nerves. I Olfactory S Smell II Optic S Vision III Occulomotor M Eye movements- ‘up/down/up-in’, pupil constriction, raising eyelids IV Trochlear M Eye movements-‘down & in-diagonal’ (superior oblique muscle) V Trigeminal S&M Sensation to head & face, including gums and teeth Movement of muscles of mastication VI Abducens M Eye movements- ‘out’ (lateral rectus muscle) VII Facial S&M Taste from anterior 2/3 of the tongue Movement of muscles of facial expression VIII Auditory S Hearing, balance (vestibuloccoclear) IX Glossopharyngeal S&M Taste from posterior 1/3 of the tongue Swallowing, salivary secretion X Vagus S&M Sensory & motor autonomic supply to most organs XI Accessory M Movement of neck muscles, voluntary swallowing & vocal cords XII Hypoglossal M Tongue movements. Cranial nerves acronym: ‘Oh Once One Takes The Anatomy Final Very Good Vacations Are Heavenly’ Sensory/motor or both: ‘Some Say Marry Money, But My Brother Says Big Brains Matter More’ 6|Page Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 ! Be able to interpret cranial nerve testing results, based on your knowledge of the nerves and the sensory and motor functions they serve. ! Outline briefly the form and function of our special sensory organs. Smell (olfaction) " Purpose: is to discriminate good food from bad food, to determine whether there is any dangers present (e.g. fire) and for memory formation. " Chemoreceptors called smell receptors or olfactory receptors detect changes in chemical concentration when dissolved in mucus in the nose and convert this chemical message into an electrical message and send it to the olfactory nerves. " The olfactory nerves the send their information along olfactory bulbs and tracts to different areas of the cerebrum. " Sense of smell reduces with age. Vision " Purpose: important for survival and for performing daily activities. " We have extremely high acuity colour vision but not as good movement detection and low light vision as other mammals. " Binocular vision gives us depth perception. " How vision works: o Light enters eye through cornea and gather light into the pupil. o The iris contracts or expands depending on amount of light making pupil smaller or larger. o Light then passes through the lens and vitreous humour and is focused on the retina. o The retina contains photoreceptors called rods and cones, which allow the retina to convert light into electrical impulses which are sent along the optic nerve to the brain. 7|Page Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 " Cones are photoreceptors that detect blue, green and red and provide sharper images than rods. " Rods are photoreceptors that are specialised for vision in dim light. Taste (gustation) " Purpose: to determine the type of food (sweet, sour, salty, bitter, umami/savoury) and identify whether it is good or bad. " Gustatory receptors (chemoreceptors) are located on taste buds which are found on papillae (elevations) on the tongue. " Four types of papillae: o Circumvallate o Fungiform (mushroom-shaped) o Foliate (striped) o Filliform (don’t contain taste buds but most numerous) " Taste buds are also found on roof of mouth and it the walls of the throat. " Chemoreceptors send information to the gustatory cortex which processes taste inputs. " Conditioned taste aversion: avoidance of certain foods due to a remembered bad experience of that food. Hearing and Equilibrium " Purpose: for communication and to be able to hear for danger and to determine where the head in relation to gravity and the earth to prevent from losing balance. " Sounds vibration is channelled in through the pinna and is transformed into mechanical vibration at the ear drum. " The ossicles (chain of three hearing bones- malleus, incus & stapes) is attached to the ear drum where the sound is enhanced and moved through the middle ear into the inner ear through the cochlea. " The cochlea contains hearing receptors situated on the basilar membrane, which when it vibrates the hearing cells (outer and inner hair cells) are displaced. " Outer hair cells amplify/attenuate/boost soft sounds and dampen loud sounds and inner hair cells transfer sound to the auditory nerve, which transfer sound to the auditory cortex in the brain. " When the head moves, so does fluid in the semicircular canals and vestibule (in inner ear) and hair cells, which activates equilibrium receptors and hearing receptors. " These receptors send information along the vestibular nerves to the cerebrum and helps detect the position of the head in space. " The Eustachian tube is normally closed but can equalise air pressure and drain mucus from the ear. 8|Page Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 ! Outline briefly the roles of the sensations of touch, pain and proprioception, and the receptors involved. ! Briefly describe the sensory information carried by the spinal nerves. " Afferent neurons in spinal nerves with carry information about touch, skin temperature, muscle length, pain and joint position. " Touch: the feeling of something present on the skin and the texture and form of it. Determined by touch receptors, temperature and pain receptors. " Pain: the feeling of a painful stimuli identified by pain receptors. " Proprioception: our sense of joint position and muscle length (knowing where are limbs are). Identified by muscle spindles (stretch and contract) and Golgi tendon organs (stretch of tendon during contraction). ! Understand the information given by the dermatome and myotome maps, and be able to outline the pattern of distribution of the spinal nerves in relation to the level of the vertebral column at which they emerge. " Spinal nerves emerge in pairs from the spinal cord between each vertebra. " There are 31 pairs of spinal nerves: 8p cervical nerves, 12p thoracic nerves, 5p lumbar nerves, 5p sacral nerves and 1p coccygeal nerves (these form nerve plexus- network of intersecting nerves). Acronym: ‘8 Crabs, 12 Turtles, 5 lizards & 5 Snakes’ " The cervical nerves exit over the top of their corresponding vertebra but the thoracic, lumbar and sacral exit under theirs. " The region that a particular nerve and its branches supply is the segment of the body corresponding to the vertebral level at which the spinal nerve emerges. " This gives us predictable maps of which parts of the body are supplied by which nerves, shown in dermatomes and myotomes. " Myotomes - Relationship between the spinal nerve & muscle (supplied by motor nerve fibres). " Dermatomes – Relationship between the spinal nerve & skin (supplied by sensory nerve fibres). Myotome Dermatome 9|Page Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 ! Be able to predict roughly the areas of the body which will be affected by damage to a particular spinal nerve, based on its vertebral level. ! Be able to use your knowledge of the peripheral nervous system to interpret the deficits and symptoms seen in clinical cases involving nervous system damage or disease. " Shingles: virus lives in the cell bodies of neurones and when activated can travel out of cell bodies, down axons and cause painful skin eruption. Where the skin eruption occurs can determine which spinal or cranial nerve the virus has travelled. " Referred pain: when pain is located away from or adjacent to the organs involved due to corresponding sensory nerves. " ! Explain how damage to a motor neurone travelling in a spinal nerve and a motor neurone travelling in the spinal cord can be distinguished by reflex testing. Patient A Patient B Stretch reflex absent Stretch reflexes +4 (normal = +2), hyperactive Voluntary movement in leg absent reflex No muscle tone in leg (flaccid Voluntary movement in leg absent paralysis) Excessive muscle tone in leg (spastic paralysis) Which one has spinal nerve at L4 damage and which has compression of motor neuron leaving brain? - Patient A has damage at L4 because no reflexes present at all meaning damage to spinal nerve because not even sensory information is reaching brain from leg. - Patient B has compressed upper motor neuron because reflexes are greater than normal therefore body cannot perform inhibitory reflex from brain to react to sensory information. 10 | P a g e Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 Topic 3: The central nervous system ! Explain what integration means in the context of central nervous system function. " The CNS is responsible for receiving, processing, collating and making sense of all the sensory information arriving. " It is also responsible for preparing and sending out an appropriate motor response to that sensory input. ! Describe how sensory neurons entering the spinal cord and motor neurons leaving it are organised & use this knowledge to predict the location of a spinal cord lesion, based on the symptoms. ! Use this knowledge to predict the location of the injury in a patient with a spinal injury, based on the functional losses. " Posterior (or Dorsal) side: back side of spinal cord, where dorsal root (sensory neurons) enter. " Anterior (or Ventral) side: front side of spinal cord, where ventral root (motor neurons) enter. " White matter (up to brain- sensory) " Grey matter (from brain- motor) " In general, the higher on the spinal cord the injury occurs, the more dysfunction the person will experience. " Injuries are referred to as complete or incomplete, based on whether any movement and sensation occurs at or below the level of injury. Types of spinal injuries: " No reflexes = damage to lower spinal nerve " Hyperreflexia= upper motor neuron damage (lack of inhibitory reflex) " An injury at C4 would affect the diaphragm and could compromise breathing. 11 | P a g e Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 ! Describe the function, location in the spinal cord and decussation point of the following tracts: spinothalamic, dorsal column, and corticospinal (pyramidal) Spinothalamic tract [ascending]: Function Carries sensory impulses from perceptions of pain, temperature and crude touch to the brain Location First order neurons enter through the dorsal root ganglions, synapse in the posterior horn on the same side and then the second order neurons cross diagonally to the other side and run up to the thalamus, synapse again and the third order neurons transmit the information to the somatosensory area of the cerebrum. Decussation immediately in the spinal cord Point E.g. information from the right side of the body runs up the left side of the spinal cord (vice versa). Dorsal column tract [ascending] Function Carries sensory information about fine touch, pressure and proprioception (muscle length & joint position) to the brain. Location First order neurons enter through dorsal root ganglion and travel into dorsal column and up to medulla where they synapse and the second order neurons cross diagonally over to the other side. They then travel up to the thalamus and synapse and third order neurons travel to the primary sensory cortex. Decussation crosses to the other side in the medulla Point oblongata E.g. information from the right side runs up the right side of spinal cord but ends up in left side of brain. Corticospinal (pyramidal) tract [descending] Function Carry motor commands from the brain to the voluntary skeletal muscles to enact movement. Location Originates in the cerebral cortex where first order neurons travel down to the medulla. Most neurons cross over in the pyramids of the medulla to the other side and travel down to the spinal cord, where they synapse and second order neurons travel to skeletal muscles. Decussation Crosses over in the brain and again in the Point medulla. E.g. motor commands to control the right side of the body run through the left side of the brain, but through the right side of the spinal cord *Decussation is the cross-over of the tract from one side to the other 12 | P a g e Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 ! Name and locate the arteries which form the brain’s blood supply, and explain how the anatomy of the blood supply helps to protect the brain from ischaemia. " The Circle of Willis is a backup system in the event that an internal carotid or vertebral artery became blocked, as blood can still travel to all parts of the brain when this happens through the circle. Circle of Willis " As the brain always needs blood there is little changes to the amount of blood it receives. " Blood gets diverted in to smaller arteries to reach all parts of the brain. ! Locate the major veins draining blood from the brain. " The ventricles (hollow cavities in brain) contain cerebrospinal fluid (CSF) which flows through the brain and is continuous with the central canal in spinal cord. " CSF is for protection, brain buoyancy, excretion of waste products and used as hormone transport medium. 13 | P a g e Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 ! Describe in general terms, the territories of the anterior, middle and posterior cerebral arteries. ! Describe the roles of the cranium, meninges, cerebrospinal fluid and blood - brain barrier in the protection of the brain. Cranium ‘car body of CNS’- Hard bony fontanelles (plates) protect brain from hard blows to it Meninges ‘Seatbelts for the CNS’ - Connective tissue that protect the brain and spinal cord. Epidural space: space above dura mater Dura mater: toughest outermost layer Subdural space: abnormal space below dura mater Arachnoid Mater: spider web like appearance Subarachnoid space: between arachnoid mater and pia mater, contains cerebrospinal fluid. Pia Mater: innermost delicate layer, holds blood vessels on tightly on the brain and spinal cord. Cerebrospinal ‘airbags of CNS’- cushions and supports the brain and spinal cord fluid Cerebrospinal fluid runs through the central canal in spinal cord and is contained within subarachnoid space in brain. Also transports nutrients, chemical messages and waste products. A spinal tap (collection of CSF) is used to provide info about CNS injury, infection or disease. Blood-brain Neural tissue is isolated from the general circulation by the blood-brain barrier barrier (BBB) which exists because the endothelial cells that line the capillaries of the CNS are extensively interconnected by tight junctions. The BBB protects the brain from "foreign substances", in that blood that may injure the brain, hormones and neurotransmitters and maintains a constant environment for the brain. Glial cells (astrocytes) form a layer around brain blood vessels and may be important in the development of the BBB. Astrocytes may be also be responsible for transporting ions from the brain to the blood. 14 | P a g e Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 ! Use knowledge of the blood-brain barrier to predict those substances which will easily cross it, and those which will not, and to predict when the blood - brain barrier may be compromised. " As the brain (neurons) are very vulnerable to changes in its environment, only substances that are required for normal functioning are allowed to cross the blood-brain barrier; o Lipid-soluble compounds (e.g. carbon dioxide, oxygen, ammonia, nicotine, anaesthetics) and lipids (e.g. steroids or prostaglandins or small alcohols) can diffuse across the membrane. o Some electrolytes (not K+) o Essential amino acids o Glucose o Caffeine o Some antibiotics o Water and ions must pass through channels in specific membranes. o Larger water molecules can only cross the capillary walls by active or passive transport. " Not permeable to: o Proteins o Protein-bound substances (e.g. drugs, hormones). o Strongly hydrophilic (water soluble) substances (e.g. Na, K) - uses specialised carrier- mediated transport. o Neurotransmitters (can interact with brain neurons) o Morphine " The BBB can be opened up by hypertension, hyper-osmolarity, radiation, infection, trauma, ischaemia, inflammation and pressure. " Development: the BBB is not fully formed at birth. " Alzheimer’s involves defective microglia and/or a defective blood brain barrier where too much beta-amyloid chemical enters brain. ! Explain why intracranial pressure (ICP) is so important for normal brain function, the factors which lead to an increase in ICP, and the result of increased ICP. ! Use your knowledge to identify clinical situations in which there would be a risk of increased ICP. " As the cranium cannot expand, if anything adds volume to the cranial contents, there will be an increase in pressure inside the cranium called Intracranial Pressure (ICP). " Factors that increase ICP: o Inflammation (e.g. meningitis, encephalitis) o Haemorrhage (bleeding, e.g. subdural haematoma) o Mass (e.g. tumour) o Hypertension o Increased CSF pressure o Stroke o Aneurysm (bulging blood vessel) o Status epilepticus (epilepsy) 15 | P a g e Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 o Space-occupying lesion (CSF is forced out of cranium, increase ICP, less blood flows to brain, structures in brain compressed, herniation of tissue). " Classic signs of raised ICP: o Deep, irregular respiration o Widening pulse pressure o Bradycardia ! Identify the major brain areas covered in the lecture and explain their functions. " The brain is divided into three sections: o Forebrain (consists of cerebrum, thalamus and hypothalamus) o Midbrain (consists of tectum and tegmentum) o Hindbrain (consists of cerebellum, pons and medulla) Structure Function Brainstem Located at base Midbrain (mesencephalon): temperature regulation, vision, hearing, of brain, sleep/wake, arousal. connects spinal Pons: arousal/level of alertness, controlled by reticular activating system, cord to cerebrum relays sensory info between cerebrum & cerebellum Has 3 structures Medulla: controls basic survival functions- respirations, maintenance of BP, (midbrain, pons, pulse, digestion, swallowing/sneezing etc. medulla) Cerebellum Inferior to the Coordinates and controls voluntary movements cerebrum Postural adjustment during movements Advance in planning rapid movements Learning of movement sequences Helps provide smooth, coordinated body movement. Cerebrum Largest part of Frontal Lobe- associated with the brain reasoning, fluency & construction of Divided into 4 speech, movement, emotions, lobes. personality and problem solving. Parietal Lobe- associated with movement, orientation, recognition, perception of stimuli of touch and proprioception. Occipital Lobe- processing of visual stimuli. Temporal Lobe- perception and recognition of auditory stimuli, short-term memory, language & comprehension. " Limbic system “emotional brain”: responsible for emotional memory and learning, recognition of emotions, emotional intelligence and linking the autonomic and endocrine responses to emotional states. o Consists of the Cingulate cortex, Hippocampus, Amygdala and hypothalamus. o Amygdala: hub for fear and aggression # Involved in emotional learning through association of a sensory experience with an emotion (usually fear). # Allows recognition of fear in people’s facial expression # Strongly activated during exposure to aversive stimuli. 16 | P a g e Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 # People with damage to amygdala: can’t show fear or recognise it in others, unable to recognise and weigh up risky behaviours avoid eye contact in social interactions Stand closer to other during contact. o Hippocampus: hub for memory # Conversion of short term to long term memory # Memory for place " Motor, sensory and association (links sensory with motor) areas of the brain. Coordination of Integration of touch & other complex movements sensations, appreciation of space & body position Complex recognition of forms Social behaviours, planning, predicting Meaning & significance of sounds Broca’s area- formulating coherent words for speech Limbic association area: Wernicke’s area- processing and Memory & emotional understanding words response ! Explain how complexity of function and evolutionary age of brain regions are related. " 500mya: The brainstem evolved, scientists say this is simplest part, controls vital functions such as pulse, BP, respirations. o Found in reptile brains. " Few 100mya: Cerebellum developed but has doubled in size. " 250mya: first mammals had limbic system for emotions " 200mya: first primates emerged the large cerebral hemispheres for higher order processes such as learning, reasoning and the development of human language. " Cerebral lateralisation: the hemisphere containing language and speech areas is your dominant hemisphere (97% of people are left-brain dominant- analytical side). ! Use this knowledge to predict the likely impact of strokes affecting these different brain regions, or to locate a stroke-affected region of the brain based on a patient’s signs and symptom " Symptoms of a stroke depend on which area(s) of the brain are involved. o Right cerebral hemisphere: left side paralysis, difficult reasoning/problem solving. o Left cerebral hemisphere: right side paralysis may disrupt the ability to speak. o Cerebellum stroke: lack of coordination (ataxia), clumsiness and balance problems, shaking, or other muscular difficulties- difficulty walking, talking, eating and ADL’s (activities of daily living) o Brain stem stroke: life threatening can disrupt vital autonomic functions. *An EEG (electroencephalogram) will be done to check the electrical activity in the brain 17 | P a g e Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 Topic 4: Introduction to Pharmacology ! List the two major branches of pharmacology and define each branch. " Pharmacology: the study of the origins, nature, chemistry, effect and use of drugs. " The two main areas of pharmacology are pharmacodynamics and pharmacokinetics. o Pharmacodynamics: the biochemical and physiological effects of drugs on the body, “what the drug does to the body”. o Pharmacokinetics: the absorption, distribution, metabolism and excretion of the drug. “what the body does to the drug”. ! Explain the various names that can be given to the same drug, and the advantages of the generic name. " Drug: a synthetic substance that affect the processes of the mind and body. Used in diagnosis, treatment or prevention of disease or can be used recreationally. " Endogenous: a substance of material that is produced within the organism. o E.g. insulin is endogenous but when artificially injected it becomes exogenous. Generic name Trade name Chemical name The official non-proprietary name of a drug, under The commercial The systematic which it is licensed and identified by the brand name given name of the manufacturer. by the company molecular Somewhat classifies the drug into a class or family. (manufacturer) who structure of the This name used in healthcare makes it. substance. " Drugs can be class by their therapeutic effect or similar action. " Examples include: o Benzodiazepines (sedatives) e.g. diazepam, midazolam o Non-steroidal anti-inflammatory drugs (NSAIDs) e.g. ibuprofen, aspirin o Opioids (narcotic analgesics) e.g. morphine, codeine o Specific serotonin reuptake inhibitors (SSRIs) e.g. fluoxetine, sertraline ! Describe the places where drugs can act, and give an example of a drug which acts on each of these types of “target”. " Most drugs bind chemically to a specific site to produce their action. They can act on: o Receptors for endogenous substances (hormones, neurotransmitters, growth factors) to hijack own receptors and manipulate them. # Opioid analgesics (stimulate opioid receptors = AGONIST), e.g. morphine # Beta blockers (block noradrenaline [beta] receptors = ANTAGONIST) # Bronchodilators (stimulate noradrenaline receptors = AGONIST), e.g. Salbutamol o Transport molecules (e.g. blood) # SSRIs (inhibit serotonin transporter = dec. in serotonin re-uptake = inc. in free serotonin = inc. serotonin effect [antidepressant]). Transporters can be inhibited or ‘loaded up’ with false substrate which competes for the natural one and be transported instead. o Ion channels (e.g. potassium-sodium channel) # Benzodiazepines (bind to GABA-A receptor and cause GABA neurotransmitter to stay at ion channel, inhibiting its excitory action, causing sedation. 18 | P a g e Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 o Enzymes # NSAIDs (inhibit enzyme cyclooxygenase [COX] which turns fatty acids into prostaglandins, inhibition reduce inflammation and pain) # ACE inhibitors (inhibit angiotensin converting enzyme, stopping conversion of angiotensin I to angiotensin II, lowers BP). Drugs can also act as false substrate, causing the wrong product to be made from the enzyme’s action. ! Define the following terms: Bioavailability, therapeutic index (or range), adverse effect, therapeutic effect, contraindication. " Bioavailability: the proportion of a drug administered which enters the circulation when introduced into the body and so is able to have an active effect. " Therapeutic index: is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes toxicity. " Adverse effect: a harmful and undesired effect resulting from a medication. " Therapeutic effect: consequence of a medical treatment in any kind, the results of which are judged to be desirable and beneficial. " Contraindication: a reason that makes it inadvisable to prescribe a particular drug or employ a particular procedure or treatment ! Explain what receptor agonists and antagonists are, and be able to give an example of the use of each in a clinical setting. " Agonist: a drug that is close enough in shape to an endogenous substance that it fools the receptor, binding to it and activating cellular activity. " Antagonist: a drug similar in shape to a receptors and has no other purpose but to block that receptor from other substances. ! Explain what the affinity of a drug for its receptor means in practical terms. ! Explain what the selectivity of a drug for its receptor means in practical terms. ! Explain what the efficacy and potency of a drug mean in practical terms. " Potency: the amount of drug needed to produce a particular size of effect. " This depends on affinity and efficacy of a drug: o Affinity: the tendency for a drug to bind with its receptor. E.g. a drug with high affinity will readily bind to its receptors and may even kick lower affinity substances out of the way. o Efficacy: the ability of drug to produce a desired or intended result. " Selectivity: the degree to which a drug will bind to certain receptors over others. This will be determined by the difference in affinity. E.g. the higher the selectivity of drugs, the less receptors it will bind to, thus the less risk of multiple side-effects ! List the four main pharmacokinetic processes, and describe the factors which can alter these processes. " Absorption: This is the movement of the drug from its administration site into the bloodstream. 19 | P a g e Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 What happens Factors that affect process Drug is taken through various route? Route of administration - How much of it is swallowed? Physiological state (e.g. cold day= - How quickly does drug reaches target from S/C, IM slower absorption rate due to slower or IV injection? blood flow) - How quick does skin absorb topical drugs? The formation of the drug If taken orally drug goes to stomach Chemical properties of the - Is drug destroyed by low pH or by enzyme pepsin? drug (size of molecules, solubility in - How quickly will stomach empty into intestines? water or lipids) Drug enters intestines - How well & how quickly is drug absorbed? - What percentage of the dose actually gets to bloodstream? " Distribution: the degree to which a drug spreads throughout the various compartments of the body. What happens Factors that affect process Drug is in blood Molecular size (can drug get - Will it be trapped there or is it able to move into through membrane?) tissues? Solubility (lipid-soluble= quicker - Can it cross the blood-brain barrier? the placental diffusion, can get into brain). barrier? Patient’s body composition - What is the blood flow to the targeted tissue like? (more fat means takes longer for - How concentrated is drug in particular tissues? drug to reach all tissues) - How much of the drug has already been taken to Removal rate by liver the liver to be destroyed? " Metabolism: the process by which drugs are broken down into inactive forms and converted into more water soluble forms ready for excretion in urine. What happens Factors that affect process Drug is brought to liver or kidneys to be detoxified. Efficiency of liver & kidneys - How much drug is in liver and broken down? Age, diet, hormone balance - How quickly is drug destroyed? Physiological state (e.g. cold day= slower metabolic rate due to conservation of energy) Drug Interactions (enzyme inhibition, enzyme induction) *Grape juice can increase bioavailability of many drugs and therefore therapeutic effect and risk of adverse effects. " Excretion: the process by which the drug metabolites are removed from the body What happens Factors that affect process Drug is sent to kidneys, diffused into urine and Filtration rate in kidneys excreted Rate of metabolism - How quickly is the drug excreted by the kidneys? Age (decreased filtration rate) - Are any of the metabolites still active and what Blood flow to kidneys does this mean for the duration of drug action? Molecular size of drug Binding characteristics (drugs that bind to plasma proteins cannot be filtered in glomerulus) Urination frequency 20 | P a g e Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 ! Explain how changes in these pharmacokinetic processes can determine whether a drug treatment is effective or not. " Changes in the pharmacokinetic processes can: o Increase/decrease duration of drug action o Bioavailability o Concentration of drug at target site o Potency of drug (drug interactions) ! Explain why the pharmacokinetics of a drug are just as important as its pharmacodynamics in deciding how useful it will be. " Pharmacokinetics is important in understanding how effective the drug will be because if the body breaks down the drug before it has reached its target site, then it will have an ineffective therapeutic effect. o E.g. if drug is broken down by low pH in stomach before it reaches target site, it becomes ineffective. " The dose and frequency of drugs will have to take into account not only the pharmacodynamics but the pharmacokinetics in order to have the therapeutic effect intended. " When taking medications regularly, the body compensates for this new addition and thus the dose may need to be increased to achieve the same therapeutic effect. " This is called Drug Tolerance. o E.g. a sustained increased stimulation of receptors on a cell by a drug will often result in a reduction in the number of receptors expressed by that cell (down regulation) and thus more of the drug is needed to have the same effect (VICE VERSA with decreasing drug doses). ! Describe the types of interactions that can occur between drugs when multiple drugs are taken, and explain some possible outcomes of these interactions. Interactions affecting absorption " Another drug (or compound) may increase or decrease the total absorption and/or rate of absorption of another drug. o E.g. Tetracyclines bind readily to ions such as Ca2+ and Mg2+ ad if they do this they are not absorbed in the stomach. So foods rich in these ions such as milk should be avoided when taking Tetracyclines. Interaction affecting distribution " The distribution of a drug that is normally highly protein bound is likely to be affected if given along with another highly protein bound drug because the drugs will be competing. o E.g. Warfarin is highly protein bound and its free concentration increases when given with paracetamol (highly protein bound), doesn’t cause large effects unless given in very high doses or if metabolism is impaired. Interactions affecting metabolism " If two drugs that are metabolised by the same enzyme are given at the same time, they will compete with each other and metabolism for both will likely slow down. o Grapefruit juice is known to inhibit one of the liver enzymes responsible for a large number of drugs (e.g. anti-arrhythmias, antihistamines, antidepressants), when combined with one of these drugs, the drug level in the blood is much higher for much longer. 21 | P a g e Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 Interactions affecting excretion " If the excretion rate of drugs changes, then the drug metabolites can accumulate in the body. This will have an effect if metabolites still have some activity. o E.g. Digoxin (heart failure medication) and Verapamil (angina & arrhythmia medication) also interact in the same way and can lead to toxic levels and cause a potentially fatal arrhythmia. Drugs can interact with each other " Two drugs with similar effects are likely to increase that effect when combined that is exaggerated out of proportion to that of each drug taken separately at the given dose may occur. (SYNERGISTIC EFFECT) o E.g. A sedating drug such as Diazepam and another CNS depressant such as alcohol can result in death due to respiratory depression. " POTENTIATING EFFECT is when one drug has an effect but the second drug does nothing but enhances the effect of the former chemical on combined exposure. o E.g. Phenergan, an antihistamine, when given with a painkilling narcotic such as Demerol intensifies its effect, there by cutting down on the amount of the narcotic needed. " Two drugs that have opposite effects will counteract each other (ANTAGONISTIC EFFECT). ! Apply these basic principles of pharmacology to problem-solving in pharmacology (as in the clinical applications session & tutorials) " Check MIMS for possible drug interactions as doctors can make mistakes as well. " Know what drugs you’re giving, their indication and their action. " If you are concerned, contact the Pharmacist to review a patient’s medications because they are the experts when it comes to drugs. " Ask patients what complementary therapies/supplements/non-prescription drugs they are taking as well because these can cause interactions with prescription drugs. o E.g. St John’s Wort, a natural herb supplement is used for depression, tiredness, fatigue and insomnia because it increases neurotransmitter serotonin. Some antidepressants such as Sertraline also increase serotonin levels so the interaction with St John’s Wort can cause serious side effects such as heart problems, shivering, seizures, agitation and anxiety because the two drugs have a SYNERGISTIC EFFECT. 22 | P a g e Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 Topic 5: Pharmacology of Major Drug Classes ! Explain the principles of chemotherapy " Chemotherapy is the chemical treatment that is designed to destroy fast-growing cancer cells within the body, however the treatment doesn’t discriminate between the body’s own fast- growing cells such as skin, hair, digestive and immune cells which causes the side-effects (e.g. hair loss, reduced immunity). " Chemotherapy aims to exploit any differences between cancer cells and your own healthy cells, however cancer cells have become very similar to own cells so that it is harder for them to be destroyed. ! Outline the targets which are exploited by antibacterial, antifungal, antiviral and cytotoxic drugs. Antibacterial drugs Bacteria vs. normal cells How antibacterials work. DNA/RNA synthesis uses different enzymes Inhibition of DNA/RNA synthesis e.g. Quinolones Bacteria have tough, thick cell wall, ours do not Inhibition of cell wall synthesis e.g. Penicillins Bacterial ribosomes are different to our Inhibition of protein synthesis e.g. tetracyclines, ribosomes. aminoglycosides Cell membrane has different structure Disruption of cytoplasmic membrane e.g. polymixins Some metabolic pathways are different Inhibition of general metabolic pathways e.g. sulphonamides Antifungal drugs Fungi vs. normal cells How antifungals work. Fungi has cell wall (like plants) Inhibiton of cell wall synthesis e.g. caspofungin, micafungin. Fungi have ergosterol in their cell membrane, Inhibition of ergosterol synthesis e.g. fluconazole, we have lipids and cholesterols ketoconazole Drugs bind to ergosterol and disrupt membrane e.g. nystatin & amphotericin Antiviral drugs Viruses vs. normal cells How antivirals work. Viruses have specific proteins on its coat to Blocking attachment of virus to cell- drugs under bind with host cell and be taken into cell. development now. Virus uncoats once inside cells and releases its Uncoating blocked by amantadine & ramantadine genetic material. (good for Influenza A) & Aridone (broad spectrum) Virus DNA directs host cell to replicate its DNA Virus replication stopped by polymerase inhibitors, reverse transcriptase inhibitors (good for herpes and HIV). Virus directs host cell to make viral coats and Assembly of new virions blocked by protease assemble new viral particles. inhibitors (good for HIV). New viral particles ‘bud off’ from host cell to Budding off blocked by neuramindase inhibitors (e.g. infect more cells. Oseltamivir (good against influenza). Cytotoxic drugs Tumour cells vs. normal cells How cytotoxic drugs work. Tumour cells have extra strand of DNA (only Inhibition of DNA synthesis and integrity difference). DNA damaging agents Inhibition of microtubule function- means DNA cannot ‘unzip’ 23 | P a g e Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 ! Briefly describe how drug resistance comes about, by giving some examples of resistance mutations which occur. " Resistance to antimicrobial and anticancer drugs can occur which is where the pathogenic cells have developed specific mechanisms for surviving anti-pathogenic drugs due to natural selection. " Drug resistance comes about through: o Pathogens mutating accidentally (mutations can be advantageous [good for organism], deleterious [bad for organism] or neutral) o Those mutations that are advantageous to the pathogen and help it survive against specific drugs designed to kill it will be passed on to future generations. [NATURAL SELECTION= SURVIVAL OF THE FITTEST] o If people overuse or misuse antibiotics, some bacteria survive, develop resistance and reproduce, spreading the resistant gene via plasmids (DNA transfer). " Examples of bacterial resistance include: o Bacterial chromosomal mutations, synthesis of enzymes that alter drug structure, prevention of drug entry into the cell or alteration of drug receptors on cell targets. ! List the major neurotransmitters mentioned in the lecture and give the major roles of each & their involvement in disease. ! Neuro- Role Involvement in disease transmitter Acetylcholine Involved in voluntary movement(skeletal Too much acetylcholine is associated muscle contraction), learning with depression (attentiveness), memory, anger/aggression, Too little in the hippocampus has sexuality and sleep been associated with dementia. Inhibit contraction of cardiac muscle Stimulates excretion of certain hormone Noradrenaline or Important for attentiveness, emotions, Norepinephrine plays a role in mood norepinephrine sleeping, dreaming, and learning. disorders such as manic depression Also releases hormone noepinephrine into the blood in ‘fight or flight’ situations to increase HR. Adrenaline or Causes vasodilation (increase BP), Too little epinephrine has been epinephrine bronchodilation (increase resps.), increase associated with depression. blood glucose and fatty acids to provide energy, all responses required for ‘fight or flight’ situation. Dopamine Regulates motor behaviour, pleasures Too much dopamine has been related to motivation (reward system), associated with schizophrenia, emotional arousal and dependency. Too little is associated with some forms of depression as well as the muscular rigidity and tremors found in Parkinson’s disease. Serotonin Regulates sleep, appetite, memory and Too little serotonin is associated with learning, temperature, mood, behaviour, depression and some anxiety muscle contraction and functioning of the disorders, especially OCD. CNS and endocrine system. 24 | P a g e Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 GABA Inhibits brain activity, sedates NS Too little GABA is associated with anxiety and anxiety disorders. Some antianxiety medication increases GABA at the receptor sites and are used treat epilepsy and trembling of people suffering from Huntington’s disease. Endorphins Link pain with emotional centres of the Endorphins have been used to treat (endogenous brain and can produce analgesia. depersonalisation disorder. opioid peptides) Elicit pleasure or euphoria during exercise, orgasm, love and eating spicy food and produce an overall feeling of well-being. ! Give an overview of how antidepressants work, and explain the main differences between the older and the newer antidepressant drug classes. " Anti-depressants works by increasing the amount of a neurotransmitter in a certain area of the brain by inhibiting the reuptake of these neurotransmitters (which stops their action). " Antidepressants are now classified into six main families from oldest to newest: o monoamine oxidase inhibitors (MAOIs), o tricyclics, and o selective serotonin reuptake inhibitors (SSRIs) o noradrenaline-serotonin reuptake inhibitors (NSRIs) o selective noradrenaline reuptake inhibitors (SNRIs) o noradrenaline-dopamine reuptake inhibitors (NDRIs) " The newer drugs are not necessarily more effective against depression but they are far more selective in their mode of action and thus have fewer side-effects and can be for long-term use. Treatment of mania " Lithium can be used to treat mania as it causes a mood stabilising effect through altering the function of a number of neurotransmitters. " If lithium fails other drugs such as anticonvulsants, sedatives or antipsychotics may be tried. " It limits the occurrence of manic or depressive episodes. " However it had a narrow therapeutic index and so blood levels need to be monitored. " Toxic doses can result in confusion, seizures and coma. " Side effects include: fine muscle tremor, nausea, vomiting, diarrhoea, polydipsia, thirst, loss of appetite and even kidney failure. ! Know the receptor sub-types for noradrenaline and acetylcholine, and the autonomic and other functions that they are responsible for. ! Use your knowledge of the major neurotransmitters mentioned to be able to predict the effects of an excess or inadequate amounts of the neurotransmitter Autonomic neurotransmitters: " Sympathetic division (fight or flight): noradrenaline & adrenaline " Parasympathetic division (rest & restore): acetylcholine Receptors for Adrenoceptors or adrenergic receptors (two main types): noradrenaline α (alpha) receptors: - α1 = found in blood vessels (causes vasoconstriction, less blood to gut, kidney & bladder, non-essential functions in fight or flight situation). 25 | P a g e Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 - α2 = found in the brain (presynaptic receptor which decrease noradrenaline release from the neurone, inhibits noradrenaline activity). β (beta) receptors: - β1 = found only on the heart (cause increase in HR and strength of beat) - β2 = found in bronchioles & blood vessel (causes bronchodilation and vasodilation, more blood to heart, lungs & muscles, essential for fight or flight response). - β3 = found in fat cells (cause mobilisation of fat, frees up energy for immediate use). Receptors for Cholinergic receptors (two main types): acetylcholine Nicotinic - Found of skeletal muscle (produce contraction) - Activated by exogenous nicotine Muscarinic - Found in brain & on organs & glands (produce parasympathetic response) - Activated by exogenous muscarin (in some mushrooms) ! Use your knowledge of the receptor subtypes and their functions to predict the actions of drugs which act at these receptors. Clinical uses for autonomic drugs " Treatment of hypertension, antihypertensives e.g. beta-blockers (β antagonist) " Reduction in risk of cardiac arrhythmia after a myocardial infarction, e.g. beta-blockers " Treatment of asthma, e.g. Salbutamol (β2 agonist) " Treatment of glaucoma= inc. pressure in eye, e.g. beta-blockers (β antagonist) " Treatment of nasal congestion " Treatment of diarrhoea, motion sickness, e.g. muscarinic antagonists " Emergency resuscitation (cardiac arrest) and anaphylaxis, e.g. β1 agonist, inject adrenalin. 26 | P a g e Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 ! Describe the mechanism of actions of the two major classes of analgesic drugs. " Pain is both a sensory and emotional experience and painful stimuli helps you remember experience which causes pain which helps you to avoid them in future (protective mechanism). " Two major classes of analgesics: o Non-steroidal analgesics (NSAIDs) o Narcotic analgesics (opiates) " NSAIDs: o Block the production of chemical stimuli of pain to the brain such as histamine. o Act by inhibiting the enzyme cyclooxygenase (COX), required for the production of a group of compounds known as prostaglandins. o This inhibition causes an analgesic, anti-inflammatory and anti-pyretic response due to pain suppression, reduction of inflammatory processes which reduce temp. o Examples: Aspirin (acetylsalicylic acid), Nurofen (Ibuprofen) & Celebrex (Celecoxib). " Narcotics (opiates) o Dampen down the emotional response from the injury itself, the number of impulses that get sent to the brain and activating an inhibitory reaction in the brain. o They are agonists at our endogenous opioid receptors (a system that ‘dampens down’ pain signals when it might be detrimental to be experiencing extreme pain such as in danger or extreme stress). o Our endogenous opioids are beta endorphin, enkephalins & dynorphin. o Examples: morphine, codeine, methadone, pethidine, fentanyl. o Effects of opioid agonists (opiates): # Analgesia # Constriction of pupils # Sedation # Cough suppression (only codeine & pholcodine) ! Use your knowledge of the mechanism of action of the analgesic drugs to be able to predict the likely side effects of members of these drug classes. Side effects of narcotics Constipation Respiratory depression or SOB Light-headedness, dizziness, drowsiness Irregular heartbeat or bradycardia Stomach upset, nausea, vomiting Anxiety Sphincter of Oddi & ureter spasms (morphine) Tremors Appetite suppression Seizures Tolerance and dependence Itching ! Use your knowledge of the mechanism of action of the analgesic drugs to be able to recognise the signs of overdose of an opioid. Classic signs of an opioid overdose: " Pinpoint pupils " Decreased respiratory rate (sometimes apnoea) " Coma " Hypotension " Convulsions Treatment of an overdose: " Use an opioid antagonist (antidote), e.g. naloxone or naltrexone 27 | P a g e Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 " In addicts a large dose may precipitate an explosive withdrawal syndrome and patient will regain consciousness. " Antagonist may be titrated to reduce respiratory depression but maintain sedation " Naloxone has a relatively short duration of action so repeat dosing required to prevent relapse. ! Briefly describe the phenomenon of tolerance and its relationship to dependence. " Tolerance: the body’s state of reduced sensitivity to a drug when it is given in regular doses. " This means larger doses are required to produce the same therapeutic effect. " Tolerance can be physiological and psychological but is reversible. " When the body becomes tolerant to a drug, it begins to function with presence of the drug. This is dependence. o E.g. for example if the drug controls bowel movements, the body slowly forgets how to control bowel movements naturally because the presence of the drug has taken over this function and now the body relies on the presence of the drug. " Dependence: is the physiological or psychological adaptation of the body to the presence of a drug. When that drug is suspended or counteracted by an antagonist, the body will go into withdrawal ! Describe how neurotransmitters are removed from the synaptic space after release, and the ways in which this removal can be manipulated using drugs. " After the action potential has been transferred to the postsynaptic neuron, the neurotransmitters in the synaptic cleft renter the presynaptic neuron through channels in the membrane. o This is called REUPTAKE! " Agonist drugs: o Bind to receptors on the postsynaptic neuron to simulate (change) or enhance a neurotransmitter’s actions. o Block the reuptake of neurotransmitters so more bind to receptors and increase the effects of that neurotransmitter. " Antagonist drugs: o Block the receptors and inactivate them (usually by taking up the space) causing the neurotransmitter's effect to be is nullified or diminished. 28 | P a g e Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 Topic 6: Introduction to Microbiology ! Define the main types of microorganism that cause disease in humans " Microorganisms or microbes is a microscopic organism, which may be a single cell or multicellular organism. " Microbes were discovered by Anton Van Leeuwenhoek on 1673 using a microscope he designed. " Louis Pasteur proved the existence of microbes and dispelled the theory of spontaneous generation. Main types of microorganisms: Fungi: o Eukaryotes, possess rigid cell wall of chitin and glucan (polysaccharides). o Can be unicellular (e.g. yeasts) or multicellular (e.g. moulds) o Live on dead plant and animal material Protozoa: o unicellular eukaryotes o have cell membrane and membrane-bound organelles (no nucleus). o some have flagella for movement o found in aqueous and soil, as well as in animals and insects o some can be seen with the naked eye Bacteria: o Unicellular prokaryote o No nucleus, membrane-bound organelles o Has cell membrane usually surrounded by cell wall o Cytoplasm contains ribosomes, DNA and granules/vesicles o Have external structure e.g. flagella, pili o Can vary enormously in size and shape (e.g. cocci, bacilli, spiral) Viruses: o No nucleus, organelles or cytoplasm but contain genetic material o Can only replicate inside host cells o Have outer protein coat Parasites (two types): o Endoparasites: live inside body # E.g. Helminth worms o Ectoparasites: live on surface of body # E.g. fleas, lice, mites ! Describe the key fungi, protozoa and multicellular parasites that infect humans ! Describe their effects on humans Fungi Healthy individuals have high resistance to fungal infections, however when immunosuppressed opportunistic fungi can alter commensal parameters and replicate dramatically. Moulds Many of human importance in food spoilage, food products and antibiotics. E,g. Penicillium mould makes Penicillin antibiotic because it produces chemicals that prevent bacteria cell wall synthesis, causes cell lyses. 29 | P a g e Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 Types of fungal infections: Superficial mycoses (outermost layer of skin or hair), e.g. tinea veriscolor Cutaneous mycoses (colonise skin, deeper into epidermis, increase invasive properties), e.g. Athlete’s foot, ring worm Subcutaneous mycoses (affect epidermis, dermis, muscle and bone. Entry via skin trauma, can be difficult to treat), e.g. mycetoma, candida albicans Systemic mycoses (infections affecting internal organs, entry by inhalation of spores, most dimorphic), e.g. Histoplasmosis (spores from soil, affects lungs), pneumocystis pneumonia. Protozoa Entamoeba histolytica = major cause of dysentery Pathogenic amoebae travel into intestinal wall and cause abscesses and ulcers o E.g. Giardia Intestinalis- attaches to host tissues in small intestine and cause a release of tissue fluids, diarrhoea, malaise (lethargy/unwell feeling/discomfort) and lots of gas. Malaria- caused by Plasmodium parasites that are injected into humans from mosquito saliva when they bite you. Disease develops in liver and invades RBCs and ruptures them. o Half of the world’s population are at risk, those in poorer nations are more at risk. Parasites Endoparasites- Helminth Worms, including: o Flatworms: flukes and tapeworms o Nematodes: roundworms Ectoparasites- o Fleas: blood-sucking parasites, can be host to pathogenic organisms. o Lice: cause redness and itching, e.g. Pediculus humanus (hair lice) o Mites: burrow into skin & lay eggs, can produce allergens, redness and inflammation indicates infection, e.g. Sarcoptes scabei (causes scabies). ! Briefly describe the structure and physiology of bacteria, and how these differ from our own cellular structure and physiology. ! List the differences between gram positive and gram negative bacteria STRUCTURE: " All bacteria possess a cell (plasma) phospholipid bilayer membrane. " Most also possess an outer cell wall, principally composed of peptidoglycan. " Most bacteria can be classified into two major groups based on their cell wall composition: o Gram-positive: # Contains a thick peptidoglycan layer on the outside of the cell wall. # Dye turns gram positive cell wall purple but no effect on gram negative. o Gram-negative: # Contains a thin peptidoglycan layer covered by an outer membrane # Also contains lipopolysaccharide (LPS) also known as endotoxin, which causes toxic effects in Gram-negative infections. " Some bacteria have: o Glycocalyx (surrounding slime layer, protects bacterium) o Flagella (attached for motility) o Pili and Fimbriae (pili for conjugation & transfer of genetic material; fimbriae for attachment to surfaces including host tissue). PHYSIOLOGY: " Cell wall: 30 | P a g e Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 o Determines cell shape and some staining properties o Protects against osmotic lysis and some toxic substances o Contains components that contribute to pathogenicity " Some bacteria produce toxins: Endotoxins Exotoxins Formed only by Gram-negative bacteria Formed by both Gram-positive and Gram- Integral part of cell wall, released on negative bacteria bacterial death (lyses). Excreted by a microorganism or released Usually produce fever in host when cell lyses Moderately toxic (though can cause Highly toxic (fatal in small doses to animals) death through systemic symptoms). Can destroy cells and disrupt normal cell Can be treated with antibiotics metabolism Can be destroyed by antibodies or heating " Bacterial growth: o Bacteria reproduce by binary fission whereas our cell replicate through mitosis. o Generation time maybe as little as 20 minutes or hours (time to reproduce) # E.g., E.coli replicates very fast and inhabit intestine and can cause severe gastroenteritis. ! Define the growth of bacteria and identification methods used " Involves 4 phases of growth: o Lag- where bacteria assess the environment that will grow in before replication. o Exponential- doubling/replicating very fast, causes huge spike in bacterium numbers o Stationary- not enough nutrients or space for any more bacteria to replicate o Decline- too many bacteria to be supported by environment, some start to die. " Pure cultures are often taken of bacteria to increase the numbers of bacteria in the sample. o Use agar plates (nutrient-rich) to feed bacteria from swab overnight Identification methods: " Gram stain: +ive = purple, -ive = pink " Other stains for flagella, capsule etc. " Identify bacterial: o Cell morphology o Colony morphology o Aerobic or anaerobic growth (or both) o Specialised nutritional requirements for growth. " Serological tests: detection of specific antibodies " Molecular techniques: Polymerase Chain Reaction (PCR) detects nucleic acid sequences " Biochemical tests: enzyme production or sugar metabolism. ! Describe the structure of a virion, and how this structure affects the antigenicity of the virus & its ability to invade cells. " Naked viruses have viral DNA and RNA surrounded by a protein shell (capsid) = protected from destruction o Viral capsid contains distinctive antigenic structure as it can resist desiccation, pH change & detergents. 31 | P a g e Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 " Enveloped viruses have outer coat (envelope) derived from host cell’s lipid bilayer = recognisable to self. o Proteins may project as spikes (peplomers) from the envelope = involved in attachment of virus to host cells. " Polymerase enzyme enables insertion into host DNA by using host’s biochemical replication mechanism. " Haemagglutinins are antigenic glycoproteins in viral surface, binds virus to host cell. " Neuraminidase are enzymes on viral surface that act on infected cell surface to release viral progeny. ! Understand how viruses replicate " Viruses do not have mechanism to correct mutations or ensure DNA stability so many mutations occur, resulting in different strains (often more virulent). " These mutations are very hard to keep up with, making treatment difficult. " The basic process of viral infection and virus replication occurs in 6 main steps: 1. Adsorption - virus binds to the host cell. 2. Penetration - virus injects its genome into host cell. 3. Viral Genome Replication - viral genome replicates using the host's cellular machinery. 4. Assembly - viral components and enzymes are produced and begin to assemble. 5. Maturation - viral components assemble and viruses fully develop. 6. Release - newly produced viruses are expelled from the host cell. ! Explain the HN naming of flu viruses. " H= haemagglutinins & N= neuraminidase (H+N) " H+N are types of spikes and enzymes on a viral cell surface. o H1N1 ‘Spanish flu’- killed up to 100 million worldwide o H2N2 ‘Asian flu’- between 1-4 million deaths o H1N1 ‘Swine flu’- declared pandemic in 2009, low mortality rate. o H5N1 ‘Bird flu’- around 240 death, millions birds killed/culled ! Apply knowledge of these microorganisms, their structure, behaviour and disease-causing potential, to clinical cases of infectious disease 32 | P a g e Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 Topic 8: Introduction to immunology ! Explain the overall purpose of the immune system " The immune system is a dynamic communication network that defends the body against foreign organism, recognises infection and initiates protective counter-measures to prevent the body being weakened by pathogens. ! Explain the role of the lymphatic system in the immune response " The lymphatic system is a network of connecting vessels that collects and filters the interstitial (or tissue) fluid called lymph through lymph nodes to remove some foreign materials. " The lymphatic system is part of the circulatory system. " It also houses and transports white blood cells to and from lymph nodes and into the bloodstream. " Lymph nodes become swollen and painful anytime your body is fighting infection. ! Outline the differences between innate and adaptive immunity Innate response Adaptive response NON-SPECIFIC to groups of microbes SPECIFIC to particular antigens Born with this immune response Builds up over time after exposure to an antigen Remains the same throughout lifetime Generally slower to respond Quicker response (first response seen) Remembers antigens for faster, greater Has no memory of antigens. response second time exposed Role is to repel attackers and prevent Systemic: Not restricted to initial site of infection invasion and colonisation of pathogens Able to respond to large number of antigens ! List the components and characteristics of innate (non-specific) immunity and outline how they operate. INNATE/NON-SPECIFIC IMMUNITY " The innate immune response includes: - physical barriers (e.g. skin, mucous membranes, cilia), - chemicals (enzymes, pH extremes, high [salt], interferons, complement, lysozyme) o lysozyme (in tears, mucus & saliva) hydrolyzes peptidoglycan in bacterial cell wall. o Cytokines: amplify and direct the immune response to affected tissues. - phagocytosis (by neutrophils, dendritic cells, eosinophils, monocytes & macrophages). o Steps for phagocytes mobilisation: 1. Leukocytosis: release of phagocytes from bone marrow in response to cytokines 2. Margination: phagocytes cling to walls of capillaries in the inflamed area 3. Diapedesis: passage of blood cells through intact capillary walls into affected tissues. 4. Chemotaxis: inflammatory chemical (chemotactic agents) promote movement of leukocytes. - natural killer cells (NK) - inflammation (triggered by stimulus that kills or injures tissue, mobilises local and systemic defences, facilitates repair and regeneration). 33 | P a g e Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 - Fever: the maintenance of body temperature greater than 37.2˚C. Within limits fever can be beneficial in inhibiting some viruses & bacteria and raise the metabolic rate (quicker mobilisation of tissue defences and accelerated repair process). " Leukocytes: Cells of the innate immune system - Granulocytes: # Neutrophils: (MOST ABUNDANT) first line of defence against bacteria, phagocytosis and activation of bacterial mechanisms, produced in bone marrow. # Eosinophils: function in inflammatory and allergic responses, phagocytosis of antibody-coated parasites, contain perioxidase & lysozyme. # Basophils: (LEAST ABUNDANT) release granules containing histamine & heparin (anti- coagulant) during inflammatory & allergic responses, have multi-lobed nucleus. - Agranulocytes: # Monocytes: circulate in blood until they find a bacterial cell, diffuse out of blood and become activated (differentiate into macrophages and dendritic cells). # Macrophages (activated monocytes): phagocytosis and activation of bacterial mechanisms, antigen presenting. o Dendritic cells (“antigen presenting cell”): phagocytosis of pathogens and presents it to MHC complex on T cells (T cell activators), long/thin dendrite-like cells. # Lymphocytes: o NK cells: circulate in blood and check MHC I tags on random cells and if it finds any foreign material by not completing signal, it release an enzyme that causes apoptosis. Effective against cancer cells and intracellular pathogens # Mast cells: release histamine and active agents to cause increased capillary permeability to allow WBCs to flow into affected areas. # basophils: promotion of allergic responses and augmentation (escalation) of anti-parasitic immunity # Pattern recognition receptors: recognise a whole range of antigens and recruits immune response when suspicious activity is identified. o Toll-Like Receptors: act like mines, if pathogens accidentally touch receptors, they will be set of and release cytokines. # Interferons (cytokines): released by host cells of pathogen (virus) to alert neighbouring cells to produce antiviral proteins. Interferons can also combat bacterial and parasitic infections, inhibit cell division (e.g. tumours), and promote or impede the differentiation of cells. They are produced by all vertebrate animals and possibly by some invertebrates as well. # Complement: protein found in blood that generates a rapid and amplified response to a given stimulus. Complements functions include: o Opsonization - enhancing phagocytosis of antigens by activating phagocytes. o Chemotaxis - attracting macrophages and neutrophils to site of infection via diapedesis (passage through intact capillary walls to site of inflammation). o Cell Lysis - rupturing membranes of foreign cells o Clumping of antigen-bearing agents. Complement is activated by three different pathways: - Classical pathway: Triggered by antibody bound to the surface of pathogen (ACQUIRED IMMUNITY) 34 | P a g e Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 - Alternative pathway: activated by the direct recognition of certain microbial structures (INNATE IMMUNITY) - Lectin pathway: activated by the binding of mannose-binding lectin to terminal mannose proteins on microbial glycoproteins and glycolipids (INNATE) ACQUIRED/SPECIFIC IMMUNITY " Components of acquired immunity include: o Lymphocytes: # T cells Produced in the bone marrow and mature in the thymus Four types: o Th- activates cytotoxic T cells and B cells o Tc- recognises targets by binding with MHC I and releasing cytokines which cause apoptosis in infected cells. o Ts- regulates the immune system by turning off the immune response when no more antigen present. o Tm- remembers specific antigens for future exposures # B cells Produced and mature in the bone marrow Some become plasma cells which produce antibodies and other become memory B cells which remember antigens to produce quicker and greater responses upon the second exposure to that antigen. o Antibodies: glycoproteins (immunoglobulins) that are specific to an antigen and work to inactivate that antigen. ! Describe how the immune system gives rise to inflammation " When a tissue is damaged or killed, the immune system responds accordingly: 35 | P a g e Downloaded by Poppy Donchi ([email protected])  lOMoARcPSD|23789778 o Causes localized redness, swelling, heat (inc. blood to area), and pain (release of histamine). o Increased capillary wall permeability allows WBC's to leak out in tissue o Promotes macrophage (phagocytic WBC's) activity o Macrophages secrete Interleukins (communication proteins among WBC's) # Interleukin-1: increases body temperature (i.e. causes a fever) This enhances the WBC's ability to protect the body Causes drowsiness - reduces the body's energy usage and stress ! List the divisions of adaptive (specific) immunity and the cells involved " Two divisions of specific immunity: o Humoral (or antibody-mediated) immunity: # Involves helper T cells and B cells binding to MHC II # Immune function performed by antibodies o Cellular (or cell-mediated) immunity: # Involves helper and cytotoxic T cells binding to MHC I # Immune function performed by cells. ! Describe how B cells are activated and the function of antibodies " Two ways: o T cell-dependent activation # An antigen is bound the MHC II and is presented to a T helper cells which recognises it as foreign and activates the B cells to differentiate into plasma and memory cells, plasma which produce antibodies to that antigen to deactivate it. # Plasma cells produce identical antibodies (clonal selection) to the antigen that activated them. Secrete 2000 antibodies/second/per cell Last approx. 4-5days (peak plasma antibody concentration at 10 days). o T cell-independent activation # In some cases B cells can attach directly to a small part of an antigen called the epitope, recognise it as foreign and then proceed to internalise the entire antigen and destroy it. Types of IgM- primary response, first circulating antibodies to appear after an infection, only antibodies: last a short time. IgG- secondary response, accounts for 70-80% of immunoglobulins, can easily leave blood and enter tissue, can cross placenta. IgA- predominant in saliva, mucus, milk and tears, also circulate in blood. IgE- attaches to basophils and mast cells to stimulate release of histamine when suitable antigen is found, functions in inflammatory responses (main immunoglobulin in allergic responses), also effective against parasitic worms. IgD-