/* === PHYSL 210 — source PDF paths + pre-extracted notes === */ /* Lecture recordings, hosted as UNLISTED YouTube videos and embedded in each lecture's video slot on the Lessons page. Keyed: moduleId -> lectureNumber (as a string) -> [recordings]. Each recording: { rec, label, yt } where `yt` is the 11-char YouTube video ID (the code after `watch?v=` or `youtu.be/`). To add a video: upload it as Unlisted on YouTube, copy its ID, and add an entry below. Missing/empty entries fall back to the existing placeholder. Example — Special Senses, Lecture 1, two recordings: ss: { "1": [ { rec: 1, label: "Recording 1: Intro to Special Senses", yt: "abc123XYZ_0" }, { rec: 2, label: "Recording 2: Taste & Smell", yt: "def456UVW_1" }, ], }, */ const LECTURE_VIDEOS = { }; const SOURCE_SLIDES = { cns: [ { label: "Lecture 1", path: "sources/cns/Central Nervous System Online Lecure 1 2025 To post.pdf" }, { label: "Lecture 2", path: "sources/cns/Central Nervous System Online Lecure 2 2025 To post.pdf" }, { label: "Lecture 3", path: "sources/cns/Central Nervous System Online Lecure 3 2025 To post.pdf" }, { label: "Lecture 4", path: "sources/cns/Central Nervous System Online Lecure 4 2025 To post.pdf" }, { label: "Lecture 5", path: "sources/cns/Central Nervous System Online Lecure 5 2025 To post.pdf" }, ], ans: [ { label: "Lecture 1", path: "sources/ans/ANS Physl210 online Lecture 1 2023.pdf" }, { label: "Lecture 2", path: "sources/ans/ANS Physl210 online Lecture 2 2023.pdf" }, ], ss: [ { label: "Lecture 1", path: "sources/ssp/Special Senses Physiology Online Lecture 1 2017 To post.pdf" }, { label: "Lecture 2", path: "sources/ssp/Special Senses Physiology Online Lecture 2 2017 To post.pdf" }, { label: "Lecture 3", path: "sources/ssp/Special Senses Physiology Online Lecture 3 2017 To post.pdf" }, ], cardio: [ { label: "Lecture 1", path: "sources/cvp/Cardiovascular Physiology Online Lecture 1 2017 To post.pdf" }, { label: "Lecture 2", path: "sources/cvp/Cardiovascular Physiology Online Lecture 2 2017 To post.pdf" }, { label: "Lecture 3", path: "sources/cvp/Cardiovascular Physiology Online Lecture 3 2017 To post.pdf" }, { label: "Lecture 4", path: "sources/cvp/Cardiovascular Physiology Online Lecture 4 2017 To post.pdf" }, { label: "Lecture 5", path: "sources/cvp/Cardiovascular Physiology Online Lecture 5 2017 To post .pdf" }, { label: "Lecture 6", path: "sources/cvp/Cardiovascular Physiology Online Lecture 6 2017 To post.pdf" }, { label: "Lecture 7", path: "sources/cvp/Cardiovascular Physiology Online Lecture 7 2017 To post pdf.pdf" }, ], cell: [ { label: "Lecture 1", path: "sources/cell/Cell Physiology Online Lecture 1 2017 To post.pdf" }, ], blood: [ { label: "Lecture 1", path: "sources/blood/Blood Physiology Online Lecture 1 pdf.pdf" }, { label: "Lecture 2", path: "sources/blood/Blood Physiology Online Lecture 2 pdf.pdf" }, { label: "Lecture 3", path: "sources/blood/Blood Physiology Online Lecture 3 pdf.pdf" }, { label: "Lecture 4", path: "sources/blood/Blood Physiology Online Lecture 4 pdf.pdf" }, { label: "Lecture 5", path: "sources/blood/Blood Physiology Online Lecture 5 pdf.pdf" }, { label: "Lecture 6", path: "sources/blood/Blood Physiology Online Lecture 6 pdf.pdf" }, { label: "Lecture 7", path: "sources/blood/Blood Physiology Online Lecture 7 pdf.pdf" }, ], nms: [ { label: "Lecture 1", path: "sources/nms/Nerve, Muscle and Synapse Physiology Online Lecture 1 pdf.pdf" }, { label: "Lecture 2", path: "sources/nms/Nerve, Muscle and Synapse Physiology Online Lecture 2 pdf.pdf" }, { label: "Lecture 3", path: "sources/nms/Nerve, Muscle and Synapse Physiology Online Lecture 3 pdf.pdf" }, { label: "Lecture 4", path: "sources/nms/Nerve, Muscle and Synapse Physiology Online Lecture 4 pdf.pdf" }, { label: "Lecture 5", path: "sources/nms/Nerve, Muscle and Synapse Physiology Online Lecture 5 pdf.pdf" }, { label: "Lecture 6", path: "sources/nms/Nerve, Muscle and Synapse Physiology Online Lecture 6 pdf.pdf" }, { label: "Lecture 7", path: "sources/nms/Nerve, Muscle and Synapse Physiology Online Lecture 7 pdf.pdf" }, ], }; const SOURCE_NOTES = { cns: [ { heading: "Overview", id: "overview", items: ["Central Nervous System (CNS)"] }, { heading: "Lecture 1 Recording 1: Introduction to the CNS", id: "lecture-1-recording-1--introduction-to-the-cns", items: ["•", "Early Brain Maps:", "•", "Not tested on", "•", "Cell Types of the Nervous System:", "•", "2 basic cell types of the nervous system: neurons and glial cells (also known as glia)", "o Neurons:", "❖ A nerve cell: functional unit of the nervous system which generates", "action potentials", "❖ Glial cells: non-neuronal cells which play a supportive role to neurons,", "both physically and metabolically", "➢ Do not generate action potentials; provide scaffolding on which", "the nervous system is built, help neurons line up closely with", "each other to allow neuronal communication, provide insulation", "to neurons, transport nutrients and waste products, and", "mediate immune responses", "❖ Comparison: Nerve → a bundle or group of axons or fibers from", "individual neurons that travel together", "•", "Organization of the Nervous System:", "•", "Central nervous system (CNS) → integrating and command center; brain and spinal cord", "•", "Peripheral nervous system (PNS) → connects the brain to peripheral structures; cranial", "and spinal nerves", "o Afferent division: sensory: axons of afferent neurons carry sensory information", "from peripheral receptors to the CNS", "❖ Sensory information can be somatic sensory, visceral sensory or special", "sensory", "➢ Somatic sensory: information on the spatial limits of the body", "➢ Visceral sensory: information on the internal organs, especially", "the abdominal organs", "➢ Special sensory: information from sight, hearing, equilibrium,", "taste, and smell (5 special senses)", "o Efferent division: motor: axons of efferent neurons carry motor information to", "the periphery", "•", "Organization of the Nervous System:", "•", "Motor division:", "o Somatic nervous system: controls the activity of our skeletal muscles; voluntary", "o Autonomic nervous system: controls the activity of smooth muscle, cardiac", "muscle and glands; involuntary", "•", "Sensory receptor detects stimuli → afferent (sensory) axon travels to CNS → cell body of", "the afferent axon is located outside the spinal cord in a posterior root ganglion (dorsal", "root ganglion) → axon enters the spinal cord → synapses with interneurons and/or", "efferent neurons → axon of efferent (motor) neuron innervate effector organs (skeletal", "muscles in the somatic division and smooth muscle, cardiac muscle and glands in the", "autonomic division)", "•", "Ganglion → collection of cell bodies located outside the CNS", "•", "Dorsal = sensory", "•", "Ventral = motor", "•", "Interneurons found entirely within the CNS", "•", "Glial Cells of the CNS:", "•", "Glial cells:", "o Astrocytes", "❖ Star-like cells", "❖ Physically support neurons → form a scaffold that holds neurons", "together", "❖ Form the blood brain barrier", "❖ Form scar tissue", "➢ Scar tissue inhibits the regeneration of severed axons in a spinal", "cord injury; barrier to the recovery of function", "❖ Turnover or recycling of neurotransmitters", "❖ Maintain electrolyte balance", "o Oligodendrocytes", "❖ Oligo = few; dendro = branches; cytes = cells", "❖ Cells with relatively few branches", "❖ Form the myelin sheath around neuronal axons", "➢ Electrically insulates segments of the axons and increases their", "conduction velocity", "o Ependymal cells", "❖ Produce cerebrospinal fluid", "o Microglia", "❖ Scavengers that ingest bacteria and cellular debris", "•", "CNS is Divided into Gray and White Matter:", "•", "CNS contains gray matter and white matter", "o Gray matter → consists of unmyelinated nerve cell bodies, dendrites and axon", "terminals.", "❖ Nuclei → clusters of cell bodies in the brain and spinal cord", "➢ Cell bodies are assembled in an organized fashion in both the", "brain and spinal cord; form layers or cluster into groups of", "neurons that have similar functions", "o White matter → consists mostly of myelinated axons and contains very few cell", "bodies", "❖ White color is from myelin sheaths surrounding the axons", "o Tracts → bundles of axons that connect different regions of the CNS", "❖ Tracts in the CNS = nerves in the PNS", "o Neural tissue has minimal extracellular matrix; relies on external support for", "protection from trauma", "❖ Support comes from an outer casing of bone, three layers of connective", "tissue membrane and fluid between membranes"] }, { heading: "Lecture 1 Recording 2: Protective Elements of the CNS", id: "lecture-1-recording-2--protective-elements-of-the-cns", items: ["•", "Protective Elements of the CNS:", "•", "Bone: Brain is encased in the skull (cranium); spinal cord runs through the vertebral", "column", "•", "Meninges:", "o 3 layers of membranes that lie between the bone and tissues of the CNS", "o Stabilizes neural tissue and protects it from bruising against the bones of the", "skeleton", "❖ Dura mater, arachnoid mater and pia mater", "•", "Cerebral spinal fluid (CSF):", "o Continuously secreted to provide physical and chemical protection", "o Found in specific spaces of the brain", "•", "Blood-brain barrier (BBB)", "o Helps maintain a stable environment for the brain", "•", "The Meninges:", "•", "3 membranes that cover the brain and the spinal cord", "•", "Dura mater", "o Outer layer", "•", "Arachnoid mater", "o Intermediary layer", "❖ Loosely tied to the pia mater, leaving a subarachnoid space between the", "two layers", "•", "Pia mater", "o Inner layer", "o Adheres to the surface of the brain and spinal cord", "•", "Meningitis → infection of the meninges", "•", " Cerebrospinal Fluid:", "•", "Found in the ventricles of the brain", "•", "Choroid plexus:", "o Thin layer of cells that line the ventricles", "o Consists of capillaries and a transporting epithelium (ie epithelial cells) which", "produce cerebrospinal fluid at a fairly steady rate", "•", "Ventricles:", "o Interconnected series of cavities filled with CSF", "•", "Cerebrospinal fluid:", "o Flows from ventricles to the subarachnoid space between the pia mater and the", "arachnoid membrane, surrounding the entire brain and spinal cord", "o Flows around the neural tissue and is absorbed back into the blood by special", "villi on the arachnoid membrane in the cranium", "o Reabsorbed into the blood in the venous system at the same rate it is produced", "o Provides mechanical protection", "o Maintains the appropriate electrolyte balance for the neural tissues", "•", "Cerebrospinal Fluid:", "•", "Hydrocephalus (water on the brain):", "❖ If reabsorption of CSF is blocked, cerebrospinal fluid accumulates and", "increases pressures in the cavities of the central nervous system and the", "spinal central canal", "❖ Skull expands in infants if not corrected surgically with a drain", "•", "The Blood-brain Barrier:", "•", "Functional barrier between the interstitial fluid and the brain", "•", "Capillaries:", "o Capillaries (outside CNS)", "❖ Porous → passages between the cells; may allow fluid containing", "electrolytes or much larger molecules or even white blood cells, to exit", "from the interior of the capillary", "o Capillaries (CNS)", "❖ Cells that form the capillaries are tightly joined; no pores", "❖ Protects neurons from large molecules that may be harmful", "❖ Barrier for molecules to cross", "➢ Glucose → brain does not have glycogen stores so glucose must", "be able to cross capillary wall regularly", "▪", "Specific transport system for glucose (carrier-mediated", "transport)", "➢ Barrier to harmful molecules", "➢ Barrier for delivering certain beneficial drugs", "▪", "Parkinson’s disease due to a deficit of dopamine;", "dopamine cannot cross through the blood-brain barrier;", "smaller precursor molecules (L-dopa) must be used"] }, { heading: "Lecture 1 Recording 2: Protective Elements of the CNS", id: "lecture-1-recording-2--protective-elements-of-the-cns-2", items: ["•", "Standard Planes of Section:", "•", "Brain can be visualized in two-dimensional (2-D) slices", "o 3 standard anatomical planes for visualizing the brain:", "❖ 1) the coronal or frontal plane → vertical plane that splits the brain into", "front and back sections", "❖ 2) the sagittal plane → vertical plane that splits the brain into left and", "right sections", "❖ 3) horizontal or transverse plane → horizontal plane which splits the", "brain into upper and lower sections", "•", "Overview of the Directions:", "•", "Cephalic flexure → crucial bend in the neural tube during embryonic development;", "a bend in the longitudinal axis of the brain", "o Why is this important? This flexure has consequences for the application of", "standard anatomical terms used to specify location", "•", "Terms used to reference the long axis of the body, which is straight:", "o Anterior means → in front of", "o Posterior → behind,", "o Superior → above", "o Inferior → below", "•", "Terms used to reference the long axis of the nervous system, which bends:", "o Dorsal → toward the back for the hindbrain; toward the top of the head for the", "forebrain", "o Ventral → toward the gut", "o Rostral → toward the top of the head for the hindbrain; toward the “rostrum”", "(snout or front) for the forebrain", "o Caudal → toward the back of the head for the forebrain; toward the tail for the", "hindbrain", "•", "Lateral view of the Brain:", "•", "Lateral view → from the side", "•", "3 main parts of the brain: cerebrum, cerebellum, brainstem"] }, { heading: "Lecture 1 Recording 4: Structures of the Brain", id: "lecture-1-recording-4--structures-of-the-brain", items: ["•", "Major Divisions of the Human Brain:", "•", "During development, the CNS forms from a long tube", "o Lumen of the tube remains in the adult brain as a fluid-filled space", "❖ Fluid-filled space → ventricular system; filled with cerebrospinal fluid", "(CSF)", "o Brain is formed from the walls of the hollow tube", "•", "Forebrain develops into two major subdivisions: cerebrum and diencephalon", "•", "Midbrain develops as a single major division", "•", "Hindbrain develops into three parts: cerebellum, pons, medulla oblongata", "•", "Brainstem: midbrain, pons, and medulla oblongata", "•", "Cerebral cortex:", "o Outer surface of the cerebrum", "o Divided into four lobes: frontal lobe, parietal lobe, occipital lobe and temporal", "lobe", "•", "Cerebrum:", "•", "Formed by two cerebral hemispheres (left and right) separated by a groove, called", "the longitudinal fissure", "o by the corpus callosum", "❖ Corpus callosum → connects left and right hemispheres; ensures", "communication between left and right hemispheres; a very large bundle", "of nerves", "•", "Cerebral cortex → outer layer of the cerebrum", "o Made up of gray matter", "❖ Neuronal cell bodies, dendrites, and synapses", "❖ Folded to provide a greater surface area in the confined volume of", "the cranium", "▪", "Folding important for brain circuitry", "▪", "A fold or ridge in the cortex is termed a gyrus (plural gyri);", "groove is termed a sulcus (plural sulci)", "•", "Cerebrum: a collective term that refers to the largest part of the four main parts of the", "brain; cerebral cortex: a specific term that refers to the outer layer of grey matter", "•", "Lateral View of the Skull and Brain:", "•", "Cranium → part of the skull that encloses the brain; made up of 8 cranial bones", "o Surrounds and protects the brain", "•", "Important bones to know: frontal, parietal, temporal bone, occipital bones", "•", "Cortex of each cerebral hemisphere is divided into 4 lobes", "o Each lobe is associated with different functions", "•", "Diencephalon:", "•", "4 major subdivisions of diencephalon:", "o Thalamus", "❖ Integrating center and relay station for sensory and motor information", "▪", "Relay station: almost all sensory information from lower parts of", "the CNS is transmitted through the thalamus on its way to the", "cerebral cortex", "❖ Integrating center: can “shape” sensory information passing through it,", "❖ Thalamus projects fibers to the cerebrum", "o Epithalamus", "❖ Pineal gland: responsible for melatonin secretion", "o Hypothalamus", "❖ Plays an important role in homeostasis and behavioral drives.", "❖ Includes the posterior portion of the pituitary gland", "▪", "Hormone secretion", "o Subthalamus", "❖ Movement regulation", "•", "Diencephalon encloses a cavity called the third ventricle", "•", "Brainstem:", "•", "Composed of heavily interconnected regions which share many similar functions and a", "close anatomical location: midbrain, pons and medulla oblongata", "•", "Connects the cerebrum with the spinal cord", "•", "Midbrain (or mesencephalon)", "o Eye movements, auditory and visual processing.", "❖ Visual and auditory processing are the processes of recognizing and", "interpreting information taken in through the senses of sight and sound", "o Contains the substantia nigra", "❖ Area rich in dopamine neurons and part of the basal ganglia/basal", "nuclei, which enables movement and coordination", "•", "Pons", "o Hindbrain", "o Connects midbrain and medulla", "o Relay station between the cerebrum and cerebellum (in that nerve fibers", "connect the cerebrum and cerebellum)", "o Coordination of breathing (along with centers in the medulla oblongata)", "•", "Medulla oblongata", "o Hindbrain", "o Where the brainstem connects to the spinal cord", "o Important in control of involuntary functions", "o Contains the autonomic centers for regulation of visceral functions", "(cardiovascular, respiratory and digestive control)", "•", "Frontal Section of Forebrain:", "•", "Cerebral cortex:", "o Thin, convoluted outer layer of the brain", "o Contains neuronal cell bodies (gray matter)", "o Neurons of the cerebral cortex:", "❖ Arranged in horizontal layers (anatomically distinct).", "❖ Arranged in vertical columns (functionally distinct).", "o Six layers numbered from the outer surface to white matter", "❖ Each layer has unique populations of cells differing in density, size,", "shape, inputs, and outputs", "•", "Cerebellum (“Little Brain”)", "•", "Little brain", "•", "Located under the cerebrum at the back of the brainstem", "•", "Control of movements", "o Processes sensory inputs and coordinates execution of movement", "o Receives input from the spinal cord and motor commands from the cerebral", "cortex and it also sends signals back into the brainstem and up to the thalamus", "and the cerebral cortex", "o Motor timing, scaling, coordination & learning", "o Balance and gait", "o Eye movements"] }, { heading: "Lecture 1 Recording 5: Functions of the CNS", id: "lecture-1-recording-5--functions-of-the-cns", items: ["•", "Functions of the Limbic System:", "•", "Functional system of an interconnected group of brain structures connected by fiber", "pathways", "•", "Part of the brain involved in behavioural and emotional responses", "o Behaviours for survival: feeding, reproduction and caring for our young, and", "fight or flight responses", "❖ Learning, emotion, a wide variety of visceral functions, such as appetite,", "sex function and integration of endocrine function", "•", "Primary components of the limbic system: (Bolded = primary structures)", "o Thalamus, hypothalamus, basal ganglia, cingulate gyrus, hippocampus,", "amygdala", "•", "Main Divisions and Functions of the CNS: (not all areas on the slide are listed in this section, as", "they are listed in the following table)", "•", "Corpus callosum", "o Nerve axons that link the left and right hemispheres of the cerebrum", "Frontal lobe", "o Personality, emotions and the control of movement", "•", "Parietal lobe", "o Skin and muscle sensation", "•", "Occipital lobe", "o Vision", "•", "Temporal lobe", "o Hearing and memory functions", "•", "Spinal cord", "o Ascending sensory axons which transmit sensory information from the body to", "the brain, and descending axons that control movement and a variety of", "autonomic functions", "•", "Functions of Major Parts of the Brain:"] }, { heading: "Lecture 2 Recording 6: The Spinal Cord", id: "lecture-2-recording-6--the-spinal-cord", items: ["•", "Spinal Cord:", "•", "Major pathway for information flowing back and forth between the brain and the body", "•", "Vertebral column:", "o Contains vertebra → boney structures of the vertebral column that supports the", "trunk and the head on the legs", "o Spinal canal", "❖ Contains spinal cord", "•", "31 pairs of spinal nerves → convey signals to and from the spinal cord", "o Paired → one member of the pair exits on the right side and the other exits on", "the left side of the spinal cord.", "o Each spinal nerve innervates a specific area of the skin called a dermatome and", "a specific set of muscles called a myotome", "•", "Dermatomes:", "o Dermatome → area of skin supplied by a pair of spinal nerves", "❖ Cervical nerves mediate sensory input from head, neck and the arms", "❖ Thoracic nerves mediate sensory information from the trunk", "❖ Lumbar, sacral and coccygeal nerves mediate sensory information from", "the legs and feet", "o Shingles", "❖ Neurons in the dorsal root ganglia become infected with a virus related", "to chicken pox", "❖ Causes bands of sores and excruciating pain in the dermatomes", "concerned", "o Spinal cord injury", "❖ Completely severing the spinal cord means no signals will come up to", "the brain or descend from the brain", "•", "Functions of the Spinal Cord:", "•", "Functions:", "o Conveys signals from sensory receptors in the body to the brain and signals from", "the brain to the effector organs in the body, such as the muscles, the heart and", "various components of the gastrointestinal tract", "o Coordinates neural reflexes", "❖ Stimulus activates a sensory receptor → receptor sends information in", "the form of action potentials through sensory/afferent neurons to the", "CNS → CNS integrates information → response initiated through action", "potentials in motor/efferent neurons.", "❖ Spinal reflexes are integrated in the spinal cord", "▪", "May be modulated by information from higher brain centers but", "they can occur without that input", "o Contains central pattern generators that control rhythmic movements (Walking,", "breathing)", "•", "Section of the Spinal Cord:", "•", "Roots → branches; a spinal nerve branches into 2 roots when it approaches the spinal", "cord", "•", "Dorsal roots → carry incoming sensory information to spinal cord; axons of afferent", "neurons enter the spinal cord from the dorsal side of the cord via the dorsal roots", "o Dorsal root ganglia → a swelling on the dorsal roots just before they enter the", "cord, contain the cell bodies of these afferent or sensory neurons", "•", "Ventral roots → carry motor information away from spinal cord; axons of efferent", "neurons leave the spinal cord on the ventral side vis the ventral roots", "•", "Spinal Cord Gray Matter:", "•", "Gray matter of the spinal cord:", "o Contains neuronal cell bodies and their dendrites, short interneurons and glial", "cells", "o Separated into horns", "❖ Projections of grey matter toward the outer surface of the spinal cord", "❖ Dorsal or posterior horn → contains cell bodies of interneurons on", "which afferent neurons terminate", "❖ Ventral or anterior horn → contains cell bodies of efferent motor", "neurons supplying skeletal muscles", "❖ Lateral horn → contains cell bodies of autonomic neurons which supply", "smooth muscle, cardiac muscle and exocrine glands", "•", "Spinal Cord White Matter:", "•", "White matter of the spinal cord:", "o Comprised of bundles of axons that travel up and down the spinal cord", "o Myelin gives the “white” color", "o These tracts convey sensory signals ascending to the brain or motor commands", "descending from the brain", "•", "Columns or funiculi – three pair of these white matter bundles", "o Posterior/dorsal, lateral, and anterior/ventral columns on each side", "•", "Tracts or fasciculi – subdivisions of each column", "•", "Interface Between PNS and CNS:", "•", "Sensory afferent axons bifurcate, or split, into ascending and descending axons once in", "spinal cord", "o Ascending axons form dorsal columns which ascend to the brainstem carrying", "sensory information to the brain", "o Descending sensory afferent axons travel caudally, or towards the tail, for 2 to 3", "spinal segments, that is about 3 to 4 centimeters", "o Every millimetre or so, for two or three spinal segments rostral and caudal to the", "bifurcation, the ascending and descending axons send branches into the gray", "matter of the spinal cord and these branches make synaptic connections with", "interneurons and motor neurons", "•", "Spinal Reflexes:", "•", "Spinal cord:", "•", "Integrating center for simple spinal reflexes", "•", "Lie entirely within the spinal cord.", "o Example from nerve/muscle/synapse section: patellar tendon or knee jerk reflex", "•", "Spinal interneurons can route sensory information to the brain through ascending tracts.", "•", "Descending pathways from the brain may exert both short-term and long-term influence", "over spinal cord reflex function", "•", "Spinal Cord Injury (2 slides):", "•", "When spinal cord is damaged at a given level, sensation from and the motor control of", "functions below that level are likely to be abnormal"] }, { heading: "Lecture 2 Recording 7: General Principles of Sensory Systems", id: "lecture-2-recording-7--general-principles-of-sensory-systems", items: ["•", "Brain Function: Cerebral Cortex:", "•", "Can be functionally divided into 3 areas: sensory, motor and associative areas", "o Sensory cortex → all cortical areas linked with sensory functions; a section of the", "cerebral cortex which is responsible for receiving and interpreting sensory", "information from different parts of the body", "o Motor cortex → responsible for planning, controlling and executing voluntary", "movements", "o Associative cortex → integrates generated visual, auditory, gustatory and other", "general sensory signals", "•", "Sensory cortex comprises the visual cortex, auditory cortex, the primary olfactory cortex,", "the gustatory cortex and the primary somatosensory cortex", "•", "Sensory Systems:", "•", "Somatic senses (or somatosensory) → information gathered from receptors associated", "with the skin, muscles, joints fascia and viscera", "•", "Special senses → senses of smell, taste, hearing, static equilibrium, dynamic equilibrium", "and sight.", "•", "Somatosensory system → part of the sensory system concerned with the conscious", "perception of touch, pressure, pain, temperature, position, movement and vibration,", "detected by receptors in the skin, muscles, joints, fascia and viscera; relays sensations", "detected in the periphery and conveys them via pathways through the spinal cord,", "brainstem, and thalamic relay nuclei to the sensory cortex in the parietal lobe", "•", "Somatosensory → relates to or denotes a sensation (such as pressure, pain, warmth)", "which can occur anywhere in the body", "•", "“You Can Only Control What You Sense”:", "o Sensory information is important in the control of movement", "o Without knowing the state of what you are controlling, you cannot control it", "•", "Sensory Systems:", "•", "Sensory pathways: Stimulus → sensory receptor that transduces stimulus into electrical", "graded potentials → action potentials travel along afferent sensory neuron to the CNS →", "signals are integrated", "o Some stimuli pass upward to the cerebral cortex, where they reach conscious", "perception but other stimuli is acted upon without our awareness", "•", "Sensory stimuli generate action potentials in sensory neurons", "o Primary sensory/ first order neurons", "o Secondary sensory/ second order neurons", "o Tertiary sensory/ third order neurons", "•", "Nervous system can modulate and shape the information at each synapse", "•", "Sensory Information:", "•", "Ascending pathway/tract → a sensory pathway that carries peripheral sensations to the", "brain", "o Somatosensory stimuli from below the neck pass along the sensory pathways of", "the spinal cord, whereas somatosensory stimuli from the head and neck travel", "through the cranial nerves", "•", "Some information does not reach the brain", "o Visceral reflexes are integrated in brainstem or spinal cord; do not reach", "conscious perception", "•", "Sensation & perception", "o Sensation → the conscious awareness of a stimulus", "o Perception → a sensation combined with an understanding of its meaning", "o Both result from processing in the cerebral cortex", "•", "Sensory Pathways:", "•", "Each major division of the brain processes a particular type of sensory information", "•", "The pathways for sound, taste, vision and somatosensory information project to the", "thalamus.", "•", "Olfactory information is not routed through the thalamus but travels directly to the", "cerebrum", "•", "Sensory Pathways:", "•", "(Images reinforce concepts from lectures: afferent/sensory, dorsal root, dorsal root", "ganglion)"] }, { heading: "Lecture 2 Recording 8: Organization of Sensory Systems: Receptors", id: "lecture-2-recording-8--organization-of-sensory-systems--rece", items: ["•", "Organization of Sensory Systems:", "•", "The sensory system can be organized as the following:", "1. Receptors", "2. Neural encoding", "❖ Modality", "❖ Intensity", "❖ Duration", "❖ Location", "3. Transmission to CNS", "4. Hierarchical organization", "5. Topographical organization", "6. Central control over afferent information", "•", " 1. Receptors: Types of Sensory Receptors:", "•", "Sensory receptors are transducers → convert stimulus energy into information that can", "be processed by the nervous system", "•", "Receptors:", "o Specialized to detect a specific stimulus", "o 5 major groups based on the type of stimulus to which they respond:", "❖ Chemoreceptors → respond to chemical ligands such as oxygen or", "molecules like glucose", "❖ Mechanoreceptors → respond to various forms of mechanical energy,", "including pressure, vibration, gravity, acceleration, and sound", "❖ Thermoreceptors → respond to temperature", "❖ Photoreceptors → respond to lights", "❖ Nociceptors → respond to noxious stimuli (stimuli that injures)", "•", "1. Receptors: Types of Sensory Receptors:", "•", "Two types of sensory receptors", "o Sensory receptors: specialized parts of sensory neurons", "1. Specialized endings of afferent axons (eg. Skin and muscle receptors) OR", "2. Separate cells that respond to the stimulus and transmit signals via synapses", "with the afferent neurons (eg. Cochlear hair cells, retinal photoreceptor cells)", "•", "Different receptor types involved in somatic sensation"] }, { heading: "Lecture 2 Recording 8: Organization of Sensory Systems: Neural Encoding: Modality and Intensity", id: "lecture-2-recording-8--organization-of-sensory-systems--neur", items: ["•", "2. Neural Encoding:", "•", "Attributes of the stimulus must somehow be preserved once the stimulus enters the", "nervous system for processing", "o 4 types of information are coded and sent to the brain in a process known as", "sensory coding: sensory type or modality, intensity, duration, and location", "•", "Sensory coding → how different stimuli are encoded by different neural activity patterns;", "quantitative and qualitative characteristics of the stimuli", "•", "2. Neural Encoding: Modality:", "•", "Neural encoding → study of how neurons represent information with electrical activity", "(action potentials) at the level of individual cells or in networks of neurons", "o Sensory receptors change many different types of information into graded", "potentials that can initiate action potentials that can travel to the CNS", "•", "The first principle of stimulus coding and processing: modality", "o Modality of a sensory input: refers to the type of sensory information that is", "transmitted", "❖ Ie: vision, sense of touch, hearing, movement are each different", "modalities", "❖ The structure of the sensory receptor determines which modality of", "stimulus it will respond to", "❖ Adequate stimulus of a receptor: the modality activating a given", "receptor or the type of stimulus to which a particular receptor responds", "in normal functioning", "•", "Different modalities are processed in different parts of the brain", "•", "The brain associates a signal coming from a specific group of receptors with a specific", "modality", "o Stimulation of a cold receptor will always be associated with cold, whether the", "actual stimulus was cold or whether an artificial depolarization of the receptor", "was the source of the stimulus", "o Labeled line codes → 1:1 association of a receptor to a sensation; each sensory", "receptor is connected to a specific pathway, or \"labeled line,\" that carries", "information about a particular stimulus to the brain", "•", "Neural Encoding: Modality:", "•", "Somatic sensation: refers to the body's ability to perceive sensory information from the", "skin, muscles, joints, and internal organs", "o 4 distinct somatic modalities, touch, proprioception, pain, and thermal sensation", "o Multiple receptors underlie somatic sensation", "•", "Neural Encoding: Modality:", "•", "Receptors for somatic sensation.", "o Tactile (Meissner's) corpuscle (Light touch)", "o Tactile (Merkel's) corpuscle (Touch)", "o Free nerve ending (Pain)", "o Lamellated (Pacinian) corpuscle (Vibration and deep pressure)", "o Ruffini corpuscle (Warmth/mechanoreceptors)", "•", "Neural Encoding: Intensity: (see also last slide in this recording)", "•", "Stimulus intensity:", "o Increased stimulus intensity causes the membrane potential at the sensory", "receptor's initial segment to become less negative", "o Once the threshold is reached, action potentials are generated", "•", "Frequency coding:", "o The stronger/greater the stimulus, the greater the change in membrane", "potential", "o This leads to a higher rate of action potential generation", "•", "Population coding:", "o The larger the stimulus, the more sensory neurons are recruited and the more", "action potentials are delivered", "•", "Temporal pattern coding:", "o Recent research suggests that firing rate regularity or the temporal pattern of", "action potentials may also encode stimulus intensity (variability in the pattern of", "firing; bursts vs steady rate of firing)", "•", "Neural Encoding: Intensity:", "•", "Stimulus intensity affects neurotransmitter release:", "o", "Increased stimulus intensity leads to more neurotransmitter release in the central", "nervous system", "•", "Membrane potential in nerve cells:", "o", "The inside of a neuron is negative relative to the outside", "o", "Resting membrane potential: ~ -70 mV", "•", "Effect of stimulus on mechanoreceptors:", "o", "Membrane distortion opens pores, allowing sodium ions to enter", "o", "Sodium influx reduces the voltage difference, making the inside less negative", "o", "Greater stimulus intensity → larger voltage change (receptor potential)", "•", "Action potential generation:", "o", "If voltage reduces to ~ -40 mV at the first node of Ranvier, sodium permeability", "suddenly increases", "o", "Voltage inside briefly becomes positive, then potassium permeability restores", "resting potential", "o", "This rapid change is called an action potential, lasting about 0.1 ms", "o", "Action potential rate is proportional to stimulus intensity", "•", "Stimulus intensity determines receptor potential and action potentials:", "o", "Small stimulus → small receptor potential, no action potentials", "o", "Larger stimulus → larger receptor potential, action potentials are generated", "o", "Strongest stimulus → even greater receptor potential, more action potentials", "•", "Action potential propagation:", "o", "Action potentials jump between nodes of Ranvier, traveling toward the CNS", "•", "Neurotransmitter release at synaptic terminals:", "o", "More action potentials → more neurotransmitter release", "o", "No action potentials → no neurotransmitter release", "o", "Higher stimulus intensity → greater excitation of spinal neurons", "•", "Neural Encoding: Intensity:", "•", "(This slide shows the 3 mechanisms of intensity coding: frequency code, population code and", "temporal pattern coding)"] }, { heading: "Lecture 3 Recording 10: Organization of Sensory Systems: Neural Encoding: Duration and Location", id: "lecture-3-recording-10--organization-of-sensory-systems--neu", items: ["•", "2. Neural Encoding: Duration: (2 slides combined)", "•", "Duration → the duration of a stimulus is coded by the duration of action potentials in the", "sensory neuron (ie how long action potentials are generated for)", "•", "Adaptation → a reduction in the response, or the number of action potentials per second, in", "the continuous presence of a stimulus", "•", "Receptors adapt differently to stimuli", "o", "Tonic receptors (slowly adapting receptors) → adapt slowly to stimuli and generate", "action potentials throughout the duration of the stimulus; stimuli that activate tonic", "receptors are parameters that must be monitored continuously by the body", "▪", "Respond the entire time the stimulus is applied; continual production of action", "potentials", "▪", "Merkel’s corpuscles, free neuron endings, Ruffini corpuscles", "o", "Phasic receptors (rapidly adapting receptors) → adapt rapidly to stimuli or respond only", "briefly each time the stimulus changes; fire when they first receive a stimulus but cease", "firing if the strength of the stimulus remains constant", "▪", "Once a stimulus reaches a steady intensity, phasic receptors adapt to the new", "steady state and turn off; allows a body to ignore information that has been", "evaluated", "▪", "To create a new signal, the intensity of the excitatory stimulus must be changed", "▪", "Pacinian corpuscles, Meissner’s corpuscles", "•", "2. Neural Encoding: Location:", "o", "Location → how to localize the position of a stimulus either on the surface of the body", "or within the body", "▪", "Mechanisms to localize the position of a stimulus:", "1. Specific tracts", "2. Receptive fields", "➢ Two-point discrimination", "3. Lateral inhibition", "•", "2: Neural Encoding: Location:", "•", "Receptive field:", "o Each sensory neuron has a receptive field, which is the area of the body it", "responds to", "1. Smaller receptive fields: greater precision in detecting stimulus location", "2. Larger receptive fields: less precision in detecting stimulus location", "o Two-point discrimination: The ability to distinguish between two closely spaced", "stimuli depends on receptor density and receptive field size", "•", "2: Neural Encoding: Location:", "•", "Two-point discrimination: best on the hands and the face and worst on the abdomen", "and proximal parts of the limbs", "o Density of receptors is highest in the skin areas with the best two-point", "discrimination", "o The surface area of the somatosensory cortex to which the sensory afferents", "project is largest in regions sub-serving the skin areas with the best two-point", "discrimination", "1. More of the surface area of the somatosensory cortex devoted to", "sensory inputs from the fingers, the thumb and the forehead, cheek,", "nose and upper lip, and less is devoted to sensory input from the", "abdomen and proximal parts of the limbs", "•", "2: Neural Encoding: Location:", "•", "A stimulus applied to any area of the skin excites many receptors as branches of the", "axons overlap with branches of neighbouring axons", "•", "Sensory afferents with receptive fields are directly in-line with the stimulus are excited", "to a greater extent, generating action potentials at a higher rate", "•", "Overlapping stimulation between neighboring receptive fields provides general", "information about the location of a stimulus", "•", "2: Neural Encoding: Location:", "•", "Lateral inhibition → to sharpen contrast by focusing the activation of the neurons on the", "centre of a stimulus", "o Focuses ascending sensory signals, enhancing spatial acuity", "o Helps sharpen stimulus localization by suppressing signals from neighboring", "neurons", "o Location of the stimulus is perceived more precisely than if there were no lateral", "inhibition", "•", "2: Neuronal Encoding: Location:", "•", "(Mechanism of lateral inhibition is shown", "•", "Lateral inhibition → focuses second-order sensory afferent firing to the centre of the", "stimulus location"] }, { heading: "Lecture 3 Recording 11: Organization of Sensory Systems: Transmission to the CNS and Hierarchical", id: "lecture-3-recording-11--organization-of-sensory-systems--tra", items: ["Organization", "•", "3. Transmission to the CNS:", "•", "Ascending pathways → neural pathways by which sensory information from the", "peripheral nerves is transmitted to the cerebral cortex", "•", "Divergence → each sensory afferent sends branches to many neurons in the CNS", "•", "Convergence → a given neuron in the CNS receives inputs from many sensory afferents", "•", "3. Transmission to the CNS:", "•", "2 major somatosensory pathways", "o Transmit information on pain/temperature and touch/pressure/muscle stretch", "1. Each sensory pathway projects to a region of the cerebral cortex", "dedicated to a particular receptive field", "2. The brain can tell the exact origin of each incoming signal", "o Anterolateral system:", "1. Pain & temperature afferents synapse on 2nd-order interneurons in", "spinal cord that cross within 2 segments and ascend in the", "spinothalamic (Anterolateral) tracts", "2. The second neuron projects through the anterolateral column of the", "cord to the thalamus, where it synapses on cortically projecting neurons", "3. Crossover of the second neuron occurs within a vertebral segment or", "two upon entering the spinal cord", "o Dorsal column system:", "1. Touch, pressure and stretch afferents from muscle & skin ascend in the", "dorsal columns; they contact 2nd-order neurons in the brainstem and", "then cross to contralateral side", "➢ Touch, pressure and stretch afferents enter the spinal cord but", "do not immediately contact interneurons; form the dorsal", "columns which ascend to the brainstem", "➢ Afferents synapse onto 2nd-order neurons in the nuclei of the", "brainstem (first synapse)", "▪", "2nd-order neurons send axons that cross over to the", "contralateral side of the nervous system at the", "brainstem", "➢ 2nd-order neurons project through the dorsal column of the cord", "to the thalamus, where it synapses on cortically projecting", "neurons.", "➢ 2nd synapse, like the anterolateral system, occurs in the", "thalamus", "o Sensory input from one side of the body ends up causing excitation of neurons", "in the brain on the opposite side", "o In the thalamus secondary sensory neurons synapse onto the tertiary sensory", "neurons, which in turn project to the somatosensory region of the cerebral", "cortex", "o Divergence at the 3rd synapse as pathways send branches to the cerebellum", "•", "4. Hierarchical Organization:", "•", "The dorsal column and anterolateral systems are organized as a three-level hierarchy", "o Integration occurs at each synapse (or level) in the hierarchy", "o Information is therefore processed at each level providing opportunity for", "modification (attenuation or blockade), enhancement, and through divergence", "to other areas, enrichment via activation of other regions of the brain and", "association cortices", "Lecture 3 Recording 12. Organization of Sensory Systems: Topographical Organization and Central", "Control over Afferent Information", "•", "5. Topographical Organization:", "•", "Somatosensory cortex → detects sensory information from the body regarding", "temperature, proprioception, touch, texture, and pain", "o Recognizes where ascending sensory tracts originate", "o Located in the parietal lobe of the brain, in a ridge of the cerebral cortex called", "the postcentral gyrus", "1. Lies directly behind the central sulcus (a deep fissure) and the primary", "motor cortex", "o Sensory homunculus → a topographic representation of the sensory distribution", "of the body found in the cerebral cortex; shows the distribution of sensory input", "to the somatosensory cortex from the different parts of the body", "1. Density of receptors for various parts of the body are not the same", "➢ Amount of the sensory cortex devoted to receiving input from", "the face and hands is relatively large, whereas that devoted to", "input from the abdomen, legs and feet is relatively small", "•", "Plasticity → maps change according to usage", "o Ie, the shoulder and arm areas in the somatosensory cortex map in people who", "had a below the elbow amputation increased at the expense of the hand areas.", "o Dynamic plasticity → maps may constantly change", "•", "6. Central Control Over Afferent Information:", "•", "The specific ascending pathways that transmit information from somatic receptors, that", "is the receptors in the framework or outer walls of the body, including skin, skeletal", "muscle, tendons, and joints, go to the somatosensory cortex", "•", "Processing of afferent information:", "o Does not end in the primary cortical receiving areas", "o Processed continues to association areas in the cerebral cortex where complex", "integration occurs", "o Cortical association areas: areas of the brain that lie outside the primary cortical", "sensory or motor areas but are adjacent to them", "1. Not considered part of the sensory pathways", "2. Receive input from primary cortices", "3. Further interpret input", "➢ May integrate input concerning two or more types of sensory", "information", "4. Organization similar for all senses", "•", "6. Central Control Over Afferent Information:", "•", "All sensory signals are subject to extensive modification at the various synapses along", "the sensory pathways before they reach higher levels of the CNS", "•", "Central descending control over ascending sensory information", "o Inhibition can come from descending pathways", "1. The brain has some control over the information that it will receive", "2. Activity descending from higher centers in the brain and brainstem can", "“screen out” certain types of sensory information by inhibiting neurons", "in the afferent pathway", "3. Inhibitory controls:", "➢ Presynaptic inhibition: directly by synapses on the axon", "terminals of the primary afferent neurons", "➢ Postsynaptic inhibition: indirectly via interneurons that affect", "other neurons in the sensory pathways", "•", "6. Central Control Over Afferent Information", "•", "Presynaptic inhibition:", "o Acts by reducing transmitter release at synapse between first-order and second-", "order sensory neurons", "o Inhibits specific sensations eg. Pain", "o Lasts several milliseconds", "•", "Postsynaptic inhibition:", "o Acts by hyperpolarizing membrane of second-order sensory neurons", "1. Moves membrane potential further away from the threshold needed for", "generating action potentials", "o Non-selective: reduces effect of all synaptic inputs", "o Lasts less than 1 millisecond", "•", "Labeled Line Codes:", "•", "Labeled line codes: allow the brain to distinguish different types of information, which is", "transmitted in the same electrical signal", "Example: touch vs vision", "1. Action potentials that arrive at the somatosensory cortex are", "interpreted as touch and action potentials that arrive at the visual cortex", "are interpreted as light", "•", "Phantom limb pain:", "o Explained by labeled line codes", "o Somatic receptors receive stimuli; if their afferent fibers are stimulated at any", "point when approaching the cortex, the mode of perception by the cortex is the", "same as when the somatic receptor is stimulated directly", "o After amputation of a limb, the remaining afferent fibers transmit to the cortex", "the mode of sensation for which they were specialized, despite the lack of", "somatic receptors at the beginning of the afferent pathway", "•", "Summary:"] }, { heading: "Lecture 4 Recording 13: Motor Systems", id: "lecture-4-recording-13--motor-systems", items: ["•", "Somatic Motor System:", "•", "Motor systems control our movements", "o Allow us to maintain balance and posture, move our eyes, body and limbs and", "communicate", "o Movements generated by motor systems can be divided into 3 classes:", "1. Reflexes → rapid, stereotyped and involuntary responses that are controlled by", "the magnitude of the eliciting stimulus; ex. withdrawing your hand from a hot", "stove", "2. Rhythmic motor behaviours → initiation and termination are generally under", "voluntary control; once activated, these patterns continue almost automatically", "in an almost reflex like manner; ex. walking, chewing or breathing", "3. Voluntary movements → most complicated movements; ex. deciding to swing", "the baseball bat when the ball is thrown, at the right time and with the right", "force", "•", "To control behaviour motor systems must:", "1. Convey accurately timed commands to many different muscles", "2. Adjust posture", "3. Consider the mechanical arrangement of muscles, bones, and joints", "•", "Somatic Motor Systems:", "•", "Motor systems rely on 3 interrelated organizational principles to create movement:", "o Motor systems receive a continuous flow of sensory information", "1. Motor control requires sensory input to accurately plan and execute", "movements; this applies to low levels of the hierarchy, such as spinal", "reflexes, and to higher levels; our ability to make movements that are", "accurate, properly timed, and with proper force depends critically on", "the sensory input that is ubiquitous at all levels of the motor system", "hierarchy", "o Components of the motor system are organized as a hierarchy of control levels", "(spinal cord, brainstem and cortical motor areas)", "1. Each level is provided with sensory information necessary for its", "particular function", "2. Cortical areas involved with planning therefore do not need to monitor", "moment-details of the response; this is done at a lower level of the", "hierarchy", "o Components of the motor system are also organized in parallel (e.g., multiple", "parallel systems, each involved in a slightly different aspect of control, all", "contribute to produce smooth coordinated movements)", "•", "Supraspinal Centers Controlling Movement:", "•", "Regions above the spinal cord (supraspinal) generate motor commands based on", "sensory input", "o Sensorimotor cortex, brainstem, cerebellum, thalamus and basal nuclei (basal", "ganglia) are the 5 brain areas involved in the middle level of motor control", "•", " Control of Bodily Movement:", "•", "Motor commands are generated in the higher centres of the brain, including the frontal", "lobes and other parts of the brain; the final common path from the brain is from the", "sensorimotor cortex; signals from the sensorimotor cortex descend to the brainstem and", "to the spinal cord motor neurons, whose axons innervate the muscle fibers.", "•", "Motor commands from the higher centers of the brain are transmitted through the", "brainstem to the spinal cord", "•", "Sensory signals from sensory afferent neurons mediate spinal reflexes and ascend to the", "brainstem, cerebellum and cerebral cortex, where they provide feedback of the evolving", "movement", "•", "Feedback also comes to the motor areas of the cortex from vision and balance centers", "(not shown)", "•", "Control of Bodily Movement:", "•", "Higher centers", "o Function: forms complex plans according to individual’s intention and", "communicates with the middle level", "o Structures: areas involved with memory, emotions and motivation, and", "sensorimotor cortex", "•", "The middle level", "o Function: converts plans received from higher centers to a number of smaller", "motor programs that determine the pattern of neural activation required to", "perform the movement; subprograms determine the movements of", "individual joints; the programs and subprograms are transmitted through", "descending pathways to the local control level", "o Structures: sensorimotor cortex, cerebellum, parts of basal nuclei, some", "brainstem nuclei", "•", "Control of Bodily Movement:", "•", "The local level", "o Function: specifies activity of muscles and joints (tension of particular muscles", "and angle of specific joints) at specific times necessary to carry out the programs", "and subprograms transmitted from the middle control levels", "o Structures: brainstem or spinal cord interneurons, afferent neurons, motor", "neurons"] }, { heading: "Lecture 4 Recording 14: Brain Motor Centers", id: "lecture-4-recording-14--brain-motor-centers", items: ["•", "Cerebral Cortex:", "•", "Cerebral cortex → planning and ongoing control of voluntary movements; functions in", "both the highest and middle levels of the motor control hierarchy", "•", "Sensorimotor cortex → includes all those parts of the cerebral cortex that act together", "to control muscle movement; somatosensory cortex and motor cortex", "o Sensorimotor cortex encompasses multiple regions involved in movement and", "sensory processing. It includes:", "1. Primary motor cortex – Responsible for executing voluntary movements", "2. Premotor area – Involved in planning and coordinating movements.", "3. Supplementary motor cortex", "4. Somatosensory cortex – Processes sensory input like touch and", "proprioception.", "5. Parietal lobe association cortex", "6. These areas work together to ensure smooth, coordinated movements", "and accurate sensory feedback.", "o A large number of nerve fibers that give rise to descending pathways for motor", "control arise from the primary motor cortex (motor cortex) and premotor area", "•", "Somatotopic Map of Major Body Areas in the Primary Motor Cortex:", "•", "A somatotopic representation similar to that of the somatosensory cortex exists in the", "primary motor cortex", "o Hand and facial representations are the largest", "o The relative sizes of body structures are proportional to the number of neurons", "dedicated to their motor control.", "•", "Basal Nuclei (Basal Ganglia):", "•", "Basal nuclei (basal ganglia) → a collection of large nuclei deep within the cerebral", "hemispheres", "o Nuclei: clusters of nerve cell bodies in the CNS", "o A subcortical collection of interacting clusters of cell bodies, and are involved in", "reward, emotional, and motor circuits", "o 5 basal nuclei (caudate, putamen, globus pallidus, subthalamic and substantia", "nigra)", "o Receive input from the cortex and provide feedback back to the cortex (via the", "thalamus) for development of motor strategies and regulation of movements", "1. Initiate movement", "2. Suppress the activity of muscles that would resist the intended", "movement", "•", "Basal nuclei (basal ganglia):", "•", "Part of the extrapyramidal system", "o A network of structures that work together to modulate and refine movement,", "particularly involuntary motor control, posture, and coordination", "•", "Involved in looping parallel circuits that regulate motor activity", "o These circuits allow signals to travel from the sensorimotor cortex to the basal", "nuclei, then to the thalamus, and finally back to the cortex, helping to modulate", "movement", "o Some circuits facilitate movement; others suppress movement; ensures smooth", "and controlled motor function", "o Damage to these circuits can lead to hypercontracted muscles (rigidity,", "spasticity) or flaccid paralysis, depending on which pathways are affected.", "o Basal nuclei dysfunction is particularly evident in movement disorders like", "Parkinson’s disease, Huntington’s disease, and dystonia,", "1. Abnormal motor control", "•", "Cerebellum (“Little Brain”)", "•", "Cerebellum:", "o Influences posture and movement indirectly by means of input to brainstem", "nuclei and (by way of the thalamus) to regions of the sensorimotor cortex that", "give rise to pathways that descend to the motor neurons.", "o Receives information from the sensorimotor cortex and the vestibular system,", "eyes, skin, muscles, joints, and tendons", "o Role in motor functioning:", "1. Provide timing signals to the cerebral cortex and spinal cord for precise", "execution of the different phases of a motor program", "➢ Timing of the agonist/antagonist components of a movement", "➢ Coordinate movements that involve several joints", "➢ Store memories of movements"] }, { heading: "Lecture 4 Recording 15: Descending Pathways", id: "lecture-4-recording-15--descending-pathways", items: ["•", "Descending Pathways:", "•", "Descending tracts → specific anatomical structures within the spinal cord that carry", "motor commands; a bundle of axons that carries motor signals from the brain or", "brainstem down to the spinal cord.", "•", "Descending pathways → refer to the functional routes that motor signals take, which", "may involve multiple tracts", "o Functionally divided into pyramidal and extrapyramidal systems", "•", "Pyramidal and extrapyramidal systems:", "o Pyramidal system: consists of two distinct pathways:", "1. Corticospinal tract → supplies the musculature of the head and neck", "2. Corticobulbar tract → supplies the musculature of the body", "o Extrapyramidal system: include brainstem pathways", "(Information on pyramidal and extrapyramidal systems found on later slides)", "•", "Descending Pathways:", "•", "Descending (motor) pathways → carry motor signals from the brain or brainstem to", "muscles via the spinal cord", "o Motor pathways provide commands to ‘move’", "1. Transmit motor commands from the brain to muscles via action", "potentials", "o Generally follow a 2-neuron chain structure: upper motor neuron and lower", "motor neuron", "1. Upper Motor Neurons (UMNs)", "➢ Initiates the signal from the brain", "➢ Originate in the primary motor cortex (pyramidal system) or", "brainstem nuclei (extrapyramidal system)", "➢ Send signals down descending tracts (CST, CBT, etc.)", "➢ Synapse with lower motor neurons in the spinal cord or", "brainstem", "2. Lower Motor Neurons (LMNs)", "➢ Relays the signal to the muscle", "➢ Originate in the ventral horn of the spinal cord or cranial nerve", "nuclei in the brainstem", "➢ Receive input from UMNs and send APs to muscles", "➢ Directly innervate skeletal muscles, leading to movement", "•", "Medullary Pyramids:", "•", "Medullary pyramids", "o Paired white matter structures located in the medulla oblongata of the", "brainstem", "o Contain motor fibers from the pyramidal system:", "1. Corticospinal tract (CST)", "➢ passes through the medullary pyramids", "2. Corticobulbar tract (CBT)", "➢ Does not extend into the spinal cord or pass through the", "pyramids", "➢ Still grouped under the pyramidal system due to its direct", "cortical control over voluntary movements of the head, face,", "tongue, and neck", "•", "Corticospinal Tract (CST):", "•", "Corticospinal tract (CST) → is a group of axons that extend from the brain to the spinal", "cord", "o Part of the pyramidal system: pass through the pyramids of the medulla", "oblongata", "o 2 neuron chain", "o Cell bodies of neurons found in the primary motor cortex and terminate in the", "spinal cord", "o Primary function of this tract is the transmission of signals for voluntary or willed", "and skilled movements", "o Voluntary control of muscle movements", "o CST conveys signals from the sensorimotor cortex through the brainstem to the", "spinal cord", "o ~ 90% of the CST crosses to the contralateral side of the nervous system at the", "brainstem level", "o Below the brainstem, CST axons synapse onto alpha motor neurons that control", "the distal muscles", "1. Alpha motor neurons or alpha motoneurons, innervate muscle fibers of", "skeletal muscle and are directly responsible for initiating their", "contraction", "o CST neurons are only one neuronal synapse away from muscles", "•", "Corticobulbar Tract (CBT):", "•", "Corticobulbar tract (CBT) → part of the pyramidal system", "o CBT runs parallel with the CST", "o CBT means the cortex to the brain stem", "1. Bulbar = “pertaining to the brainstem”, a pathway that begins in the", "primary motor cortex and ends in the brainstem", "o 2 neuron chain that ends in brainstem", "1. CBT neurons end at the midbrain, pons or medulla; they synapse in", "nuclei, which contain the cell bodies of the cranial neurons, which are", "the lower motor neurons; the cranial nerves will then innervate muscles.", "o Voluntary control of movements of muscles of the head, face, tongue, neck", "(pharynx and larynx)", "o CBT synapses with cranial nerve nuclei in the brainstem before reaching the", "medulla", "1. Still classified as part of the pyramidal system because it originates in", "the primary motor cortex and follows a direct, voluntary motor", "pathway—just like the CST", "•", "Brainstem Pathways:", "•", "Extrapyramidal system", "o Do not pass through the medullary pyramids", "o Axons from neurons in the brainstem also form pathways that descend into the", "spinal cord to influence motor neurons", "1. Originate in brainstem", "o Axons of most of the brainstem pathways remain uncrossed and affect muscles", "on the same side of the body (although a few do cross over to influence", "contralateral muscles)", "o Coordination of the large muscle groups of the trunk and proximal portions of", "the limbs used in the maintenance of upright posture, in locomotion, and in", "head and body movements when turning toward a specific stimulus", "1. Involuntary and automatic muscle control (muscle tone, balance,", "posture, reflexes and locomotion)", "•", "Brainstem Pathways of the Extrapyramidal System:", "•", "Do not pass through the medullary pyramids; travel through the tegmentum of the", "brainstem", "o Central region of the brainstem", "o Extends through the midbrain, pons, and medulla", "•", "Plays a crucial role in motor control, sensory processing, and autonomic functions", "•", "Contains brainstem nuclei where descending pathways originate", "•", "Pyramidal vs Extrapyramidal Systems:", "•", "Summary of the pyramidal and extrapyramidal systems"] }, { heading: "Lecture 4 Recording 16: States of Consciousness", id: "lecture-4-recording-16--states-of-consciousness", items: ["•", "States of Consciousness:", "•", "Consciousness → a state of arousal or awareness of self and environment; includes", "states of consciousness and conscious experiences", "o States of consciousness: refers to whether a person is awake, asleep, drowsy", "o Conscious experiences: refers to experiences a person is aware of such as", "thoughts, feelings, perceptions, ideas, dreams, reasoning during any of the", "states of consciousness", "•", "Electroencephalogram (EEG):", "•", "EEG → allows measuring of the electrical activity on the scalp using electrodes which are", "often fixated on an EEG cap", "o Comprises amplified voltage fluctuations recorded between pairs of electrodes", "on the scalp", "•", "Electroencephalogram (EEG):", "•", "Voltage fluctuations seen on EEG are made up of summated synchronous post-synaptic", "potentials of many neurons", "•", "Wave forms vary with behavioural states, specifically in terms of attention, arousal, sleep", "and dreaming", "•", "Epileptic seizures: voltage fluctuations over particular parts of the brain can become very", "large and conversely, in the vicinity of brain tumours where neurons have died, the EEG", "is small or absent", "•", "Used to verify brain death", "•", "Sleep-Wakefulness States:", "•", "Sleep has been extensively studied, with various stages correlated to specific EEG", "patterns.", "•", "Two main phases of sleep:", "o NREM (non-rapid eye movement) sleep", "o REM (rapid eye movement) sleep", "•", "Wakefulness and transition to sleep:", "o Alert wakefulness → High-frequency, low-amplitude beta rhythm.", "o Relaxed wakefulness → Transition to alpha rhythm (lower frequency, higher", "amplitude).", "o Relaxed drowsiness → Decreased alpha wave amplitude and frequency.", "•", "Three stages of NREM sleep:", "o Stage N1 (light sleep): Alpha waves decrease, replaced by theta (4-8 Hz) and", "delta (< 4Hz) waves", "o Stage N2: Alpha waves replaced by random, larger amplitude waves", "o Stage N3 (deep sleep): Increased theta and delta wave activity", "•", "REM sleep (paradoxical sleep):", "o Characterized by dreaming and rapid eye movements.", "o EEG patterns resemble alert wakefulness (beta rhythm).", "o Despite active brain activity, muscle tension is low, except for the diaphragm and", "eye muscles", "•", "EEG Records:", "•", "Sleep → EEG shifts toward slower-frequency, higher-amplitude wave patterns", "o Theta rhythm and delta rhythm", "•", "NREM → high amplitude and slow frequency waves; also called slow wave sleep", "•", "Each successive stage characterized by slower frequency/higher amplitude waves", "•", "Awake State EEGs:", "•", "As a person becomes increasingly drowsy, their wave pattern transitions from beta", "rhythm to predominantly alpha rhythm", "•", "Timing of Sleep States:", "•", "Sleep occurs in cycles—typically five cycles per night", "•", "Each cycle lasts about 90 minutes, alternating between light and deep sleep", "•", "REM sleep increases as morning approaches, starting short and gradually lasting longer", "•", "Stages progress in a specific order:", "o N1 → N2 → N3 (deep sleep) → N2 → REM sleep", "•", "Uninterrupted sleep follows a repetitive pattern, with four to five cycles per night", "•", "REM sleep in young adults makes up 20–25% of total sleep time", "•", "REM sleep fraction declines with age, meaning older adults spend less time in REM sleep", "•", "Brain Structures Involved in the Sleep-Wakefulness Cycles:", "•", "Circadian rhythm regulates sleep-wake cycles (~8 hours of sleep, ~16 hours awake)", "o Sleep cycles alternate between NREM and REM sleep during the sleep portion of", "the circadian rhythm", "•", "Brainstem and hypothalamus nuclei play a crucial role in sleep regulation", "•", "Reticular formation:", "o Major integration and relay center for essential brain functions", "o Coordinates motor control, cardiovascular and respiratory systems, and states of", "consciousness", "o Connects the brainstem with widespread areas of the brain and spinal cord", "•", "Reticular activating system (RAS):", "o Includes clusters of neurons and neural pathways from the brainstem and", "hypothalamus", "o Distinguished by anatomical distribution and the neurotransmitters they release.", "o Neurons of the RAS project widely across the cortex and thalamus, influencing", "EEG patterns", "o Activation and inhibition of RAS neurons mediate transitions between", "wakefulness and sleep", "•", "Brain Structures Involved in the Sleep-Wakefulness Cycles:", "•", "Reticular Activating System (RAS) controls wakefulness and sleep via nuclei in the", "brainstem and hypothalamus", "•", "Suprachiasmatic nucleus (SCN) in the anterior hypothalamus serves as the circadian", "pacemaker", "•", "Morning: Activates orexin-producing neurons, promoting wakefulness", "•", "Evening: Regulates melatonin secretion, preparing for sleep", "•", "Orexins (neuropeptides):", "o Maintain the awake state", "o Produced in the hypothalamus, with widespread projections to the cortex and", "thalamus", "o Stimulate action potentials in monoaminergic neurons of the brainstem RAS", "•", "RAS neurons release norepinephrine, serotonin, and histamine, supporting wakefulness", "•", "Sleep center in the pre-optic nucleus (hypothalamus):", "o Inhibits the RAS via GABA, reducing orexin levels to facilitate sleep", "•", "Damage to RAS can result in coma, highlighting its role in consciousness regulation", "•", "Transitions to the Awake and Sleep States:", "•", "Wakefulness:", "o Orexin-producing neurons are activated by:", "1. Suprachiasmatic nucleus (hypothalamus) as part of the circadian rhythm", "2. Low blood glucose (negative energy balance), promoting wakefulness", "and food-seeking behavior", "3. Limbic system activity, triggering movement and exploration", "o Orexin neurons stimulate the release of monoamines:", "1. Serotonin, noradrenaline, and histamine", "2. These inhibit the sleep center and activate the cerebral cortex via the", "thalamus", "•", "Sleep:", "o Sleep center (ventrolateral pre-optic nucleus, hypothalamus) is activated by:", "1. Gradual increase in adenosine concentration due to metabolic activity", "o Neurons in the sleep center release inhibitory neurotransmitter GABA,", "suppressing:", "1. Brainstem and hypothalamus neurons, including those that release", "monoamines.", "2. Orexin-producing neurons (reducing wakefulness)", "o Result: Reduced activation of monoaminergic neurons in the reticular activating", "system, leading to less stimulation of the thalamus and cerebral cortex"] }, { heading: "Lecture 5 Recording 17: Learning and Memory", id: "lecture-5-recording-17--learning-and-memory", items: ["•", "Learning and Memory:", "•", "Learning → acquisition of information as a consequence of experience", "•", "Memory → the relatively permanent storage form of learned information", "•", "Memory encoding → the neural processes that change an experience into the memory of", "that experience", "•", "Types of Memory:", "•", "Types of Memory:", "•", "Memory can be classified by duration:", "o Short-term memory: lasts from seconds to minutes", "o Long-term memory: can persist for days to years", "•", "Short-Term Memory:", "o Registers and retains incoming information briefly, allowing conscious recall.", "o Example: Remembering a phone number long enough to dial it", "o Essential for higher mental activity and maintaining awareness of the present", "environment", "o Vulnerable to disruptions, such as:", "1. Coma, deep anesthesia, electroconvulsive shock, and reduced blood", "supply—all interfere with brain electrical activity", "o Requires ongoing neural activity (graded/action potentials)", "o Often referred to as \"working memory\" when used in cognitive tasks", "•", "Long-Term Memory:", "o Short-term memories can become long-term through a process called", "consolidation", "o Consolidation varies in duration, from seconds to minutes", "o Memory storage involves distinct brain regions, differing for:", "1. Declarative memory (facts, events)", "2. Procedural memory (skills, habits)", "•", "Model for Memory Formation:", "•", "Memory storage in the brain remains an unsolved problem", "•", "Long-term potentiation (LTP):", "o A model suggesting that frequently used synapses increase in effectiveness over", "time", "•", "Long-term memory formation:", "o Involves changes in gene expression, leading to the production of new cellular", "proteins", "o These proteins may contribute to:", "1. Increased synapse numbers after memory formation", "2. Structural changes in synapses, such as more receptors on the", "postsynaptic membrane", "•", "Neural plasticity:", "o The brain’s ability to change structurally and functionally in response to activation", "•", "Long-term Potentiation at Glutaminergic Synapses:", "•", "Glutamate is the most common excitatory neurotransmitter in the CNS", "•", "Glutamate receptors on the postsynaptic neuron include:", "•", "AMPA receptors", "•", "NMDA receptors", "•", "AMPA and NMDA receptor activity plays a key role in long-term potentiation (LTP)", "•", "Intense synaptic firing leads to:", "•", "Structural and chemical changes that strengthen synaptic signaling", "•", "Enhanced synaptic responsiveness during future activation", "•", "LTP is the fundamental mechanism behind learning and memory"] }, { heading: "Lecture 5 Recording 18: Language", id: "lecture-5-recording-18--language", items: ["•", "Language:", "•", "Language as a Complex Code", "•", "Involves listening, seeing, reading, and speaking", "•", "Requires sensory input (hearing via the auditory cortex, vision via the visual cortex)", "•", "Involves processing in multiple regions of the cerebral cortex", "•", "Motor coordination is necessary for vocalization and writing", "•", "Brain Hemispheres and Language Specialization", "•", "The left hemisphere controls somatosensory and motor functions for the right side of the", "body, and vice versa", "•", "In 90% of people, the left hemisphere specializes in language:", "o Conceptualizing and producing speech/writing", "o Neural control of speaking/writing", "o Recent verbal memory", "•", "Even 70% of left-handed or ambidextrous people use the left hemisphere for speech", "•", "The right hemisphere mainly processes emotional aspects of language", "•", "Gender Differences in Language Processing", "•", "Females use both hemispheres for some language tasks", "•", "Males primarily use the left hemisphere for language", "•", "Speech:", "•", "Broca's area (frontal lobe):", "o Motor aspects of speech", "1. Production of speech, controlling the muscles of the larynx, tongue and", "lips", "o Lesions result in motor aphasia (Slurring speech)", "•", "Wernicke's area (temporal lobe):", "o Comprehension of language", "o Association of visual, auditory and tactile input with words", "o Lesions result in sensory aphasia (Difficulty in understanding the meaning of", "sensory inputs)", "•", "Speech:", "•", "This slide contains an example of sensory aphasia", "o eg. A person is handed a pen; when asked what it is, she says it’s a spoon; when", "asked to use it, she writes her name; this indicates that the sensory to motor", "transformation is separate from sensory to cognitive transformation"] }, { heading: "Lecture 5 Recording 19: Neurodegenerative Diseases", id: "lecture-5-recording-19--neurodegenerative-diseases", items: ["•", "Conditions that progressively damage and destroy parts of the nervous system, particularly the", "brain", "•", "Neurodegeneration → the progressive loss of structure and function of neurons, eventually", "leading to neural death", "•", "Most consistent risk factor for developing a neurodegenerative disorder: increasing AGE", "•", "Common neurodegenerative diseases:", "•", "Alzheimer’s disease → dementia - loss of cholinergic neurons in the basal forebrain,", "hippocampus, frontal and parietal cortex", "•", "Parkinson’s disease → movement disorder and loss of dopaminergic neurons in substantia", "nigra (part of Basal nuclei/ganglia)", "•", "Amyotrophic lateral sclerosis (ALS) → loss of motoneurons (except for eye muscles and", "sphincters)", "•", "Huntington’s disease → movement disorder from loss of dopaminergic neurons in", "striatum (part of Basal nuclei/ganglia)", "•", "Dementia:", "•", "Dementia:", "o A neurodegenerative disease", "o The loss of cognitive functioning — thinking, remembering, and reasoning — to", "such an extent that it interferes with a person's daily life and activities", "o Underlying mechanism may be related to a build-up of proteins in the brain that", "interferes with how the brain functions or works", "o Different protein build-ups are seen in different types of dementia", "o Types: Alzheimer's, vascular dementia", "•", "Alzheimer’s Disease:", "o Primary neurodegenerative cause of dementia", "o Progressive neurodegenerative disease leading to severe cognitive decline,", "impacting memory, speech, and recognition abilities", "o Pathology: synaptic damage and the loss of cholinergic neurons, particularly in", "critical brain regions, such as the basal forebrain, hippocampus, frontal and", "parietal cortex", "•", "Neuropathology of Alzheimer’s Disease (2 slides):", "o Neuropathological features of Alzheimer’s disease include:", "1. Senile (amyloid) plaques:", "➢ Extracellular deposits of beta-amyloid protein (Aβ)", "▪", "In the tissue between nerve cells", "▪", "Aβ is a fragment of a larger protein", "▪", "Clump together to form amyloid plaques", "▪", "Toxic effect", "2. Neurofibrillary tangles:", "➢ Tangles of hyperphosphorylated tau protein accumulated inside", "the neuron in the cytoplasm, axons, and dendrites", "➢ Can no longer properly transport materials essential to the", "neuron’s", "survival;", "neuron", "degenerates", "and", "affects", "communication", "3. Synaptic loss", "➢ Defects in axonal transport, loss of dendritic spines, pre-synaptic", "terminals, and axons", "•", "Cholinergic Hypothesis of Alzheimer’s Disease:", "•", "Acetylcholine (ACh) is involved in memory, attention, learning etc", "•", "Degeneration of the cholinergic neurons", "•", "β-amyloid affects cholinergic neurotransmission and causes a reduction in choline uptake", "and release of ACh", "•", "Risk Factors for Alzheimer’s Disease:", "•", "Age", "o Greatest known risk factor for Alzheimer's disease", "o Most AD cases have a late onset (65 years and older)"] }, { heading: "Lecture 5 Recording 20: Neurodegenerative Diseases: Parkinson’s Disease", id: "lecture-5-recording-20--neurodegenerative-diseases--parkinso", items: ["•", "Review: Basal Nuclei (Basal Ganglia):", "•", "(This slide is a review of the basal nuclei)", "•", "Parkinson’s Disease:", "•", "A degenerative, progressive disorder affecting neurons in the substantia nigra pars", "compacta (SNpc) of basal nuclei/ganglia", "o 2 regions of SN: pars reticulata (SNpr) and pars compacta (SNpc)", "o Pars compacta region of the substantia nigra contains dark dopamine containing", "neurons", "o Dopaminergic neurons involved in control of body movement and muscle tone", "o Degeneration of these neurons in Parkinson’s disease disrupts voluntary motor", "control", "•", "“Idiopathic” (unknown cause) but a combination of genetic and environmental risk factors", "•", "Symptoms of Parkinson’s Disease:", "•", "These are the symptoms of PD (bolded symptoms are the most common symptoms)", "o Parkinsonian gait", "➢ Slowness of movement (bradykinesia)", "➢ Shuffling steps", "➢ Reduced arm swing", "o Emotionless face", "o Asymmetric resting tremor", "o Postural instability", "o Impaired balance", "o Rigidity", "o Freezing (akinesia)", "•", "Parkinson’s Disease Treatment:", "•", "Symptoms of PD appear after 60 – 70% of dopaminergic neurons in SNpc are lost; typically", "occurs over 5 – 10 years", "•", "Life expectancy is 15 – 25 years after symptoms appear", "•", "Treatment:", "o Goal: to increase dopamine in substantia nigra", "o L-Dopa (Levodopa; precursor to dopamine)", "o Dopamine cannot cross the blood-brain barrier but L-Dopa can", "o L-dopa is converted to dopamine in the brain and stimulates dopaminergic", "receptors", "o Dramatic reduction of symptoms in first year but may lead to dyskinesia if taken", "in high doses for a long time", "•", "Deep brain stimulation (DBS)", "•", "Alternate treatment", "•", "Stimulation of different regions of basal ganglia can be effective at reducing symptoms"] }, ], ans: [ { heading: "Overview", id: "overview", items: ["Autonomic Nervous System (ANS)"] }, { heading: "Lecture 1 recording 1: Introduction to the Autonomic Nervous System", id: "lecture-1-recording-1--introduction-to-the-autonomic-nervous", items: ["•", "What is the Autonomic Nervous System?:", "▪", "Autonomous → It carries out its functions involuntarily or below the level of", "consciousness", "▪", "Functions:", "1.", "Maintains homeostasis or the constancy of the internal environment of our", "bodies", "2.", "Fight or flight system: it is involved in activation of emergency mechanisms or", "our response to stress", "3.", "Rest or digest: housekeeping functions (ie digestion)", "•", "Overview of the Nervous System:", "▪", "2 anatomical divisions of the nervous system: the central nervous system (CNS) and the", "peripheral nervous system (PNS)", "▪", "CNS: consists of the brain and the spinal cord", "o Neural control center", "o Receives incoming information, analyzes and organizes it, and initiates", "appropriate action", "▪", "PNS: found outside the CNS", "o Consists of cranial and spinal nerves and sensory receptors", "o 2 divisions: afferent /sensory division and efferent /motor division", "➢ Afferent /sensory division: carries information detected by receptors to", "the CNS.", "❖ The afferent /sensory division comprises afferent nerves, which", "carry sensory information from sensory receptors towards the", "CNS", "❖ Sensory information:", "–", "Somatic sensory or somatosensory: sensory", "information on touch, pain and temperature", "–", "Visceral sensory: sensory information from internal", "organs", "–", "Special sensory: sensory information from special", "sense organs, which includes visual, olfactory and", "auditory sensation", "➢ Efferent /motor division: carries information from the CNS to effectors,", "such as glands and muscles, that carry out actions directed by the CNS", "❖ The efferent /motor division is divided into two subdivisions:", "–", "Somatic nervous system/ somatic motor: somatic", "motor nerves control voluntary movements of", "skeletal muscle and mediation of the involuntary", "reflex arc", "–", "Autonomic nervous system (ANS) or autonomic", "motor: autonomic motor nerves target smooth", "muscle, cardiac muscle, and glands", " Involuntary, or not under conscious control", " Composed of the sympathetic division, the", "parasympathetic division, and the enteric", "nervous system.", " Smooth muscle is muscle tissue in which the", "contractile fibrils are not highly ordered. It is", "found in hollow organs, such as the GI tract, the", "bladder, uterus, blood vessels, and other", "internal organs. The smooth muscle is", "responsible for the contractility of these organs.", " Cardiac muscle is muscle found in the heart.", " Glands include those found in the GI tract, the", "salivary glands, and sweat glands, for example.", "➢ Afferent neuron → a neuron that relays sensory information to the CNS", "➢ Efferent neuron → a neuron that relays motor commands from the CNS", "to target tissues", "➢ Nerve → a group of nerve fibers traveling together in the PNS; contains", "the fibers or axons of neurons; may contain both afferent and efferent", "axons or fibers; Information may travel in both directions in a nerve", "➢ Neuron → a nerve cell", "•", "Cranial Nerves: (do not memorize each of the 12 cranial nerves, their names/what they", "innervate/do)", "▪", "12 cranial nerves", "o Emerge directly from the brain, including the brainstem", "o Do not emerge from the spinal cord", "o Vagus nerve or nerve 10", "➢ Important for the parasympathetic division", "•", "Spinal Nerves: (do not memorize what each nerve innervates)", "▪", "31 pairs of spinal nerves", "▪", "All are mixed nerves: contain both afferent and efferent fibers", "▪", "Organization of the spinal cord: cervical nerves, thoracic nerves, lumbar, sacral, and", "coccygeal"] }, { heading: "Lecture 1 recording 2: Somatic and Autonomic Nervous Systems", id: "lecture-1-recording-2--somatic-and-autonomic-nervous-systems", items: ["•", "Efferent Nerves of the PNS: Somatic vs Autonomic", "▪", "Efferent neurons:", "o SNS: motor information is transmitted from the CNS to the target organ, which", "is skeletal muscle", "o ANS: motor information is transmitted from the CNS to the target organ which", "is either smooth muscle, cardiac muscle, or glands", "▪", "SNS:", "o Single neuron from CNS to skeletal muscle", "➢ Cell body of the neuron is found in the CNS and the axon extending to", "the target organ, the skeletal muscle", "o Single synapse at the skeletal muscle", "➢ Synapse between the neuron and the skeletal muscle", "o Activation of the somatic neuron only results in skeletal muscle contraction", "➢ When the neurotransmitter acetylcholine is released from the axon", "terminals, this results in contraction of the skeletal muscle", "➢ Inhibition of skeletal muscle contraction takes place in the CNS ie no", "command will travel down the axon to the skeletal muscle", "➢ Axons of somatic motor neurons travel in cranial or spinal nerves to the", "effector or target organ, the skeletal muscle", "➢ Axons of the somatic efferent neurons are large and myelinated", " Conduction is fast", "▪", "ANS:", "o Organized into a chain of two neurons in series that connect the CNS and the", "target tissue/organ", "➢ Neurons are linked by a synapse: an anatomically specialized junction", "between two neurons where electrical activity in one neuron influences", "the excitability of the other", "➢ 2 neuron chain made of preganglionic and postganglionic neurons", " Preganglionic neuron → first neuron of the", "chain; cell body in the CNS; axon extends from", "the CNS to the ganglia", " Ganglia → where the preganglionic neuron", "synapses with the postganglionic neuron; a", "cluster of neuronal cell bodies OUTSIDE the CNS", " Postganglionic neuron → second neuron of the", "chain; cell bodies of postganglionic neurons are", "found outside the CNS in ganglia (ganglia plural;", "ganglion singular); axon leaves ganglia and", "travels to target tissue", " Myelination: axons of the preganglionic", "neurons are lightly myelinated; axons of the", "postganglionic neurons are unmyelinated", " Can have excitation or inhibition at target tissue", "depending on the transmitter that is", "released and the type of receptor to which the", "neurotransmitter binds to", "•", "Comparison of Somatic and Autonomic Nervous Systems:", "▪", "(Table is a summary of the somatic and autonomic nervous systems; most of this was", "discussed above)", "▪", "SNS:", "o Control is voluntary; we decide to move", "o Neurotransmitter always ACh", "▪", "ANS:", "o Control is Involuntary; actions take place without consciousness or willingness", "o Neurotransmitter can be: ACh, NE, E"] }, { heading: "Lecture 1 recording 3: Organization of the Autonomic Nervous System", id: "lecture-1-recording-3--organization-of-the-autonomic-nervous", items: ["•", "Subdivisions of the ANS:", "▪", "Both the sympathetic (SNS) and parasympathetic (PSNS) systems are composed of a", "two-neuron chain", "o Length of the axons of the preganglionic and postganglionic fibers differ", "between the two systems", "o PSNS:", "➢ Ganglion is located very close to or even within the walls of the target", "organ", "➢ PSNS preganglionic neuron has a long axon, as a result of a long distance", "between the spinal cord and the ganglion", "➢ PSNS postganglionic neuron has a short axon, since it only needs to", "travel a short distance from the ganglion to reach the target organ", "➢ PSNS response is more isolated (do not have mass discharge as in SNS)", "o SNS:", "➢ Ganglion is located close to the spinal cord", "➢ SNS preganglionic axon is very short and the postganglionic axon is very", "long", "➢ Postganglionic neuron synapses to its target organ, located further away", "➢ Short SNS preganglionic axon allows much branching and mass", "discharge, which is where many organs or tissues are activated", "following activation of the SNS", "•", "Location of Cell Bodies of Preganglionic Fibers:", "▪", "Cell body of the first neuron (preganglionic neuron) is found in the CNS system (either", "brain or spinal cord)", "▪", "Cell body of preganglionic neuron is found in the CNS and the axon leaves and travels to", "a ganglion, where it synapses with the cell body of the postganglionic neuron", "▪", "Cell bodies of preganglionic neurons in the SNS and PSNS leave the CNS at different", "levels", "▪", "SNS → cell bodies of the first neuron are found in the thoracic and lumbar regions of", "the spinal cord", "o Cell bodies are found in the thoracic region from T1 to T12, and in the lumbar", "region from L1 to L2", "▪", "PSNS → cell bodies are found in the cranial and sacral regions", "o Cell bodies are found in the brain stem and the sacral region of the spinal cord", "➢ Axons of parasympathetic preganglionic fibers are contained in cranial", "nerves III, VII, IX, and X (cranial nerve X is also called the vagus nerve)", "➢ Cell bodies of preganglionic neurons are also found in the sacral region,", "from S2 to S4", "•", "Sympathetic Nervous System: Thoracolumbar:", "▪", "Also called thoracolumbar division (cell bodies of preganglionic neurons are found in the", "thoracic T1 to T12 and lumbar L1 to L2 regions of the spinal cord)", "(Image: view of the spinal cord from the back or dorsal view)", "▪", "Sympathetic ganglia", "o Sympathetic chain/trunk (paravertebral ganglia – run parallel to spinal cord)", "➢ Chain of ganglia running parallel to the spinal cord on each side", "➢ Spinal cord: has white and grey matter", " Dorsal and ventral roots join to form the spinal", "nerve", " Dorsal root – pathway into spinal cord; carries", "sensory information to the spinal cord; contains", "axons of afferent/sensory neurons", " Ventral root – pathway leaving spinal cord;", "carries motor information away from the spinal", "cord; contains axons of efferent/motor neurons", "– Axons of the autonomic neurons leave the", "spinal cord via the ventral roots as", "autonomic neurons take motor", "information to the target tissue (smooth", "muscle, cardiac muscle, or glands)", "•", "Sympathetic Nervous System:", "▪", "Collateral ganglia", "o Second set of ganglia in the SNS", "o Also called pre-vertebral ganglia", "o Ganglia located in front of the vertebral column", "➢ 3 collateral ganglia are: celiac ganglion, the superior mesenteric", "ganglion, and the inferior mesenteric ganglion", "➢ With collateral ganglia, a sympathetic pre-ganglionic axon leaves the", "spinal cord, passes through the sympathetic trunk, and then travels on", "to a collateral ganglion where it synapses with a post-ganglionic neuron", "➢ Lie close to the viscera (internal organs; more specifically the abdominal", "organs)", "➢ Innervate abdominal and pelvic viscera"] }, { heading: "Lecture 1 recording 4: Sympathetic Pathways", id: "lecture-1-recording-4--sympathetic-pathways", items: ["•", "ANS: Sympathetic Division:", "▪", "Preganglionic sympathetic fiber has its cell body in the lateral region of the grey matter.", "Axon of preganglionic fiber leaves the spinal cord by the ventral roots.", "▪", "3 pathways a sympathetic preganglionic fiber can take when it leaves the spinal cord:", "1. Synapse immediately with a postganglionic neuron in sympathetic ganglion at", "same level", "2. Travel up or down the chain and synapse in ganglia at other levels", "3. Pass through chain without synapsing, continue to collateral ganglion as", "splanchnic nerve", "▪", "Communicating rami → branches, or connections, between the spinal nerve and the", "ganglia; ramus is a branch; communicating as the fibers/axons of neurons travels within", "them", "1. White ramus communicans → the branch that leads into the ganglion from the", "spinal nerve. The white ramus is white because it is carrying a myelinated", "preganglionic fiber; it is the myelin that makes it appear white.", "2. Grey ramus communicans → the branch that goes back into the spinal nerve.", "The grey ramus is grey because it is carrying an unmyelinated postganglionic", "fiber.", "•", "Sympathetic Pathways:", "▪", "(This slide shows more closely the communicating rami)", "▪", "Rami", "o Allow “communication” as they allow nerve fibers to travel through them"] }, { heading: "Lecture 1 recording 5: The Sympathetic Nervous System and the Adrenal Medulla", id: "lecture-1-recording-5--the-sympathetic-nervous-system-and-th", items: ["•", "Functions of the Sympathetic System:", "▪", "(See table; when you learn the effects think of what your body is doing during a", "stressful/fearful situation and what is a priority in that situation in your body)", "▪", "Dominates during the fight or flight response when our body is stressed", "▪", "Adrenal medulla – only receives sympathetic innervation (no parasympathetic", "innervation)", "▪", "Blood vessels – smooth muscle of most blood vessels in the body receives only", "sympathetic innervation (no parasympathetic innervation) which constricts the blood", "vessels; blood vessels of skeletal muscle receives sympathetic innervation that can", "dilate the vessels", "▪", "Sweat glands – receive only sympathetic innervation (no parasympathetic innervation)", "•", "The Adrenal Medulla:", "▪", "Adrenal medulla", "o Part of the adrenal glands which are found just above the kidneys, one on either", "side of the body", "o Contains an outer cortex and an inner medulla", "o Innervated by sympathetic preganglionic neurons; there are NO postganglionic", "neurons innervating the adrenal medulla", "➢ Adrenal medulla itself acts like a modified sympathetic postganglionic", "neuron, but it does not have an axon or a cell body", "➢ A sympathetic preganglionic neuron has its cell body in the CNS; it has a", "short axon which innervates the adrenal medulla", "➢ Neurotransmitter released from the preganglionic neuron binds to", "receptors on the adrenal medulla causing the adrenal medulla to", "release its secretions into the bloodstream", " Adrenal medulla releases epinephrine (80%)", "and norepinephrine (20%) into blood; as they", "are released into the blood they are called", "hormone", " Norepinephrine and epinephrine will travel", "through the blood to various target tissues and", "organs to produce a response; actions will stop", "when they are broken down in the liver", " Release of norepinephrine and epinephrine into", "the blood allows these hormones to reach", "organs or tissues that do not receive nervous", "innervation; their effects are also prolonged in", "the body as they must reach the liver to be", "broken down"] }, { heading: "Lecture 2 recording 6: The Parasympathetic Nervous System", id: "lecture-2-recording-6--the-parasympathetic-nervous-system", items: ["•", "Parasympathetic Nervous System: Craniosacral:", "▪", "PSNS preganglionic fibers", "o Originate in the brainstem and sacral regions of the spinal cord;", "➢ Preganglionic fibers travel in cranial nerves III, VII, IX, and X", "➢ Vagus nerve (cranial nerve X) carries 75% of all parasympathetic fibers", "innervating various organs/tissues", "➢ Preganglionic cells bodies are also found at the S2 and S4 levels of the", "spinal cord", "•", "Parasympathetic Pathway:", "▪", "Terminal ganglia", "o Only set of ganglia in PSNS", "o Preganglionic fiber is long and the postganglionic fiber is short; the ganglia are", "therefore found close to the organ that is innervated; the ganglia may also be", "within the walls of the organ that is innervated", "•", "Functions of the Parasympathetic System:", "▪", "(See table; when you learn the effects think of what your body is doing during a relaxing", "situation and what is a priority in that situation in your body)", "▪", "Dominates during the rest or digest response when our body is relaxed/not stressed", "▪", "Adrenal medulla –no parasympathetic innervation", "▪", "Blood vessels – smooth muscle of most blood vessels in the body does not receive", "parasympathetic innervation; exception is the penis and clitoris where parasympathetic", "stimulation dilates blood vessels", "▪", "Sweat glands – no parasympathetic innervation"] }, { heading: "Lecture 2 recording 7: Dual Autonomic Innervation", id: "lecture-2-recording-7--dual-autonomic-innervation", items: ["•", "Dual Autonomic Innervation (slide 1):", "▪", "Most target organs and tissues receive dual autonomic innervation or innervation from", "both the SNS and PSNS", "▪", "Nerve fibers are efferent or carry motor commands to target organs and tissues", "•", "Dual Autonomic Innervation (slide 2):", "▪", "Tone → a background level of activity maintained by both sympathetic and", "parasympathetic divisions", "o The sympathetic and parasympathetic divisions are never completely off; there", "is always a low level of activity in either division", "➢ When one system becomes active, the other system turns down its", "activity; There is a balance between sympathetic tone and", "parasympathetic tone in accordance with the body's needs", "➢ Activated reciprocally → activity of one system will increase and the", "activity of the other system will decrease", " Fight or flight response: activity of the", "sympathetic system increases and activity of", "the parasympathetic system decreases", " Rest or digest response: activity of the", "parasympathetic system increases and the", "activity of the sympathetic system decreases", " Provides more control: one division turns up its", "activity and the other turns down its activity to", "give more control over body responses", "•", "Dual Autonomic Innervation (slide 3):", "▪", "Most body organs and tissues receive both sympathetic and parasympathetic", "innervation", "▪", "Exceptions to dual innervation:", "o Adrenal medulla, most blood vessels in the body and the sweat glands receive", "sympathetic innervation only", "➢ Do not receive parasympathetic innervation", "▪", "Antagonistic effects of the SNS and PSNS:", "o Antagonistic = opposite", "➢ Example: GI tract: SNS decreases the activity of the GI tract, decreasing", "contractility and digestive secretions; PSNS increases the activity of the", "GI tract, increasing contraction and digestive secretions", "➢ Example: Heart: SNS acts to increase heart rate and the PSNS acts to", "decrease heart rate", "▪", " Cooperative effects of the SNS and PSNS:", "o Cooperative = working together", "➢ Example: salivary glands: both divisions stimulate saliva production, but", "the type and volume of saliva produced varies; SNS stimulates", "production of a small amount of a thicker saliva; PSNS stimulates", "production of a large amount of a watery saliva", "➢ Example: male reproductive system: PSNS is responsible for erection in", "males, while the sympathetic division is responsible for emission", "▪", "Both divisions can have excitatory and inhibitory effects", "o It is not correct to say that the sympathetic system is always excitatory and the", "parasympathetic system always inhibitory", "➢ Activity depends on the target tissue, neurotransmitter released and", "the receptor to which neurotransmitter binds"] }, { heading: "Lecture 2 recording 8: Chemical Transmitters of the ANS", id: "lecture-2-recording-8--chemical-transmitters-of-the-ans", items: ["•", "Chemical Transmitters:", "▪", "Cholinergic → releases acetylcholine (ACh)", "▪", "Adrenergic → releases norepinephrine (NE)", "▪", "Preganglionic neurons", "o Release ACh in both the SNS and PSNS", "➢ Ach is the major transmitter at all ganglia in the autonomic nervous", "system", "➢ Adrenal medulla", " Receives only sympathetic innervation from a", "preganglionic fiber; release ACh which then", "binds to receptors on the adrenal medulla", " Adrenal medulla acts like a modified", "sympathetic postganglionic fiber; ACh released", "from a preganglionic fiber binds to receptors on", "the adrenal medulla", "▪", "Parasympathetic postganglionic fibers", "o Release ACh at target tissues/organs which binds to receptors on target tissues", "▪", "Parasympathetic postganglionic fibers", "o Sympathetic postganglionic fibers innervating most of the target tissues release", "the neurotransmitter NE which then binds to receptors on the target tissue", "o Some target tissues innervated by sympathetic postganglionic fibers release ACh", "➢ Tissues where ACh released: sweat glands and the blood vessels of", "skeletal muscle", "▪", "Adrenal medulla", "o E and NE are released from the adrenal medulla into the bloodstream which", "travel to their target tissues and bind to receptors on those target tissues", "•", "Events at a Cholinergic Nerve Terminal:", "▪", "ACh → major transmitted release from the preganglionic fibers in both the SNS and", "PSNS", "▪", "Events at a cholinergic nerve terminal: these are events at a preganglionic nerve", "terminal in both the SNS and PSNS", "o ACh → synthesized from acetyl-CoA and choline in the nerve terminal", "➢ Reaction catalyzed by an enzyme called choline acetyltransferase", "➢ ACh is then packaged into vesicles in the nerve terminal", "➢ An action potential travels down a preganglionic fiber, causing the", "opening of voltage-gated calcium channels in the nerve terminal", "➢ Calcium enters the nerve terminal down its electrochemical gradient,", "increasing the concentration of calcium in the nerve terminal", "➢ Increased concentration of calcium causes the vesicles to move to and", "fuse with the membrane", "➢ Ach is then released by exocytosis", "➢ Synapse is between the preganglionic neuron and the postganglionic", "neuron; Ach binds to receptors on the membrane of the postsynaptic", "neuron (receptors that bind ACh are called cholinergic receptors)", "➢ Ach cannot remain within the synapse indefinitely and must removed", "from the synaptic cleft to terminate the response to this action", "potential so that the nerve terminal is ready for the arrival of the next", "action potential", " An enzyme called acetylcholinesterase, breaks", "down ACh to choline and acetate", " Choline is recycled back into the nerve terminal", "by a carrier system which can take this choline", "back into the nerve terminal to be used again to", "make more ACh", " Acetate breaks down to carbon dioxide and", "water", "•", "What is a Varicosity? (2 slides)", "▪", "Postganglionic fibers in the ANS do not terminate in a single swelling like the synaptic", "knob seen at the ganglia of preganglionic fibers", "o Where the axons of postganglionic fibers enter a given tissue, they contain", "numerous swellings called varicosities", "➢ Varicosity → swellings along the axon branches of a postganglionic", "neuron; site where the neurotransmitters are made and stored in", "vesicles; release neurotransmitters along a significant length of the axon", "and therefore over a large surface area of the effector tissue", " Neurotransmitter may affect many cells", "simultaneously", " Found on both sympathetic and", "parasympathetic postganglionic neurons", "•", "Events at a (Nor)Adrenergic Varicosity:", "▪", "Varicosities → swellings present near the ends of the postganglionic fiber", "▪", "Sympathetic postganglionic fiber", "o Releases NE", "➢ Synthesized from the amino acid tyrosine which is taken up into the", "varicosity", "➢ Tyrosine is converted to dopa and dopamine", "➢ Dopamine is taken up into vesicles where it is converted to NE", "➢ NE is stored in vesicles until it is an action potential comes down the", "sympathetic postganglionic fiber and causes the opening of calcium", "channels", "➢ Calcium moves into the cell, raising the intracellular calcium level", "➢ Increased calcium causes the vesicles containing NE to move to and fuse", "with the membrane", "➢ NE is released by exocytosis into the synaptic cleft to bind to adrenergic", "receptors (adrenergic = binds NE) on the target tissue/organ", "➢ Stimulatory effects of NE are terminated by the uptake of NE into the", "varicosity; the whole molecule is taken up and not broken down", "➢ NE can then be repackaged into vesicles and stored, available for future", "release", "➢ Some NE may diffuse away from the synaptic space and is broken down", "by enzymes in various tissues which is why we need to synthesize new", "NE; the primary mechanism for terminating NE action is reuptake into", "the nerve terminal", "•", "Summary: Transmitters of the ANS", "▪", "ACh", "o Released at all autonomic ganglia", "o Released from all parasympathetic postganglionic fibers", "o Released from sympathetic preganglionic fibers innervating sweat glands and", "blood vessels of skeletal muscles", "▪", "NE", "o Released from most sympathetic postganglionic fibers", "o Release from adrenal medulla (along with E)"] }, { heading: "Lecture 2 recording 9: Receptors of the ANS", id: "lecture-2-recording-9--receptors-of-the-ans", items: ["•", "Receptors:", "▪", "Cholinergic receptors → receptors that bind to ACh; 2 types of cholinergic receptors:", "nicotinic and muscarinic", "o Nicotinic receptors", "➢ NM → (nicotinic muscle) found in the somatic nervous system; found in", "skeletal muscle at the neuromuscular junction; bind to ACh released", "from somatic motor neurons to cause muscle contraction", "➢ NN → (nicotinic nerve) found in the autonomic nervous system; found", "on the cell bodies of the postganglionic neurons at all autonomic", "ganglia; found in ganglia in both the sympathetic and the", "parasympathetic divisions; bind to ACh released from the preganglionic", "endings", "➢ NN → ionotropic receptor – a receptor which is also a ligand-gated ion", "channel or a channel which has a binding site for a ligand", " When the ligand binds to the receptor, a", "channel in the receptor opens, allowing ions to", "pass through; a single protein that acts as both", "a receptor and an ion channel", " ACh is the ligand; ACh binding to the NN", "receptor opens the channel, allowing sodium", "and potassium ions to move through; sodium", "moves into the neuron and potassium moves", "out but there is a larger movement of sodium", "through the channel into the neuron, bringing", "in positive charge; this results in a", "depolarization of the postganglionic neuron and", "the production of an EPSP or an excitatory", "postsynaptic potential", "•", "Receptors (slide 2):", "▪", "Cell bodies of all postganglionic neurons in both the SNS and PSNS contain the NN type", "of nicotinic receptor", "▪", "Adrenal medulla also contains the NN type of nicotinic receptor", "•", "Receptors (slide 3):", "▪", "Muscarinic receptors", "o Cholinergic receptors", "o 5 subtypes (M1 to M5)", "o Found on the effector cell membranes, or on the target tissues", "o Metabotrophic receptors", "➢ Receptor is coupled to a G-protein signal transduction mechanism", "➢ Binding of ACh to a muscarinic receptor causes excitation or inhibition", "of the target tissue through a G-protein coupled mechanism", "•", "Receptors (slide 4):", "▪", "Adrenergic receptors", "o Bind NE or E", "o 2 types: alpha (2 subtypes) and beta (3 subtypes) adrenergic receptors", "o Found on the effector cell membranes, or on the target tissues", "o Metabotrophic receptors", "➢ Receptor is coupled to a G-protein signal transduction mechanism", "➢ Binding of NE/E to an adrenergic receptor causes excitation or inhibition", "of the target tissue through a G-protein coupled mechanism", "•", "Receptors (slide 5):", "▪", "ACh", "o Released from parasympathetic postganglionic neurons", "o Binds to muscarinic receptors found on the target tissue", "▪", "NE", "o Released from sympathetic postganglionic neurons", "o Binds to adrenergic receptors found on the target tissue", "▪", "SNS", "o Sympathetic postganglionic neurons innervating sweat glands and blood vessels", "of skeletal muscle release ACh", "➢ ACh binds to muscarinic receptors found on sweat glands or blood", "vessels of skeletal muscle", "▪", "Adrenal medulla", "o Hormones E and NE bind to adrenergic receptors on their target tissues"] }, { heading: "Lecture 2 recording 10: Receptors of the ANS", id: "lecture-2-recording-10--receptors-of-the-ans", items: ["•", "Structure of Nicotinic Receptors:", "▪", "NN type nicotinic receptor", "o Ionotropic → membrane-bound receptor proteins that respond to ligand", "binding by opening an ion channel and allowing ions to flow through", "o Made up of 5 subunits", "➢ Ring-shaped structure with a pore down the middle", " 2 alpha subunits which have the binding sites", "for ACh", " Ionotropic receptors are", "•", "Nicotinic Receptors:", "▪", "NN type of nicotinic receptor found at all autonomic ganglia", "o Found on the cell membrane of postsynaptic neurons in both the sympathetic", "and parasympathetic systems", "▪", "Mechanism:", "o ACh is released from the preganglionic neuron and binds to a receptor on the", "postganglionic neuron", "o Binding of ACh to each of the two alpha subunits causes the ion channel in the", "center of this molecule to open up allowing sodium and potassium to move", "through", "➢ More sodium enters the cell than potassium leaves the cell, bringing", "with it positive charge", "o An excitatory postsynaptic potential, or an EPSP, is produced", "o EPSP will cause the opening of voltage-gated sodium channels allowing a much", "bigger influx of sodium ions and generation of an action potential", "•", "Structure of Muscarinic and Adrenergic Receptors:", "▪", "Metabotropic receptors", "▪", "7 transmembrane spanning domains: single polypeptide chain that threads back and", "forth across the plasma membrane 7 times", "•", "Muscarinic and Adrenergic Receptors:", "▪", "Found in the membrane of the target tissue", "▪", "Both muscarinic and adrenergic receptors are metabotrophic receptors", "▪", "Mechanism of action involves a G-protein signal transduction pathway", "o ACh or NE/E bind to their respective receptors in the membrane of the target", "tissue to activate proteins called G proteins", "▪", "G proteins affect the activity of an enzyme or an ion channel in the membrane", "▪", "This change in activity will then induce a series of steps in the cell that will eventually", "produce a response in the cell"] }, { heading: "Lecture 2 recording 11: The ANS", id: "lecture-2-recording-11--the-ans", items: ["•", "Convergence and Divergence:", "▪", "Convergence and divergence exist in the nervous system", "o Convergence → numerous preganglionic neurons form synapses with a single", "postsynaptic neuron; a coming together of information as multiple presynaptic", "neurons affect the activity of one postsynaptic neuron", "o Divergence → a small number of presynaptic neurons form synapses with a", "larger number of postsynaptic neurons; a spreading out of information as a", "small number of presynaptic neurons form synapses with a larger number of", "postsynaptic neurons", "•", "Divergence at the Ganglia:", "▪", "In the ANS divergence exists at the ganglia", "o SNS exhibits a greater degree of divergence than the PSNS", "➢ PSNS: the ratio of preganglionic neuron synapsing with postganglionic", "neuron is between 1 and 3; more specific/localized responses when", "PSNS is activated", "➢ SNS: the ratio of preganglionic neuron to postganglionic neuron can be", "anywhere between 1 and 20", " In the SNS when the system is activated, there", "is a more diffuse response than in the", "parasympathetic system", " During the fight-or-flight response, mass", "discharge occurs where many organs and", "tissues in the body are affected by sympathetic", "activity.", "•", "Integrating Centers for Autonomic Reflexes:", "▪", "Reflexes in the ANS are integrated at different levels in the CNS", "o Spinal cord", "➢ Regions such as the sacral region can act as integrative centers for", "autonomic reflexes, such as urination, defecation, and erection", "➢ The brain is able to influence these reflexes", "o Brainstem", "➢ Medulla oblongata plays a role in reflexes, such as blood pressure", "regulation, salivation, swallowing, vomiting, and respiration", "o Hypothalamus", "➢ The head ganglion of the autonomic nervous system", "➢ Regulates temperature and sending messages down the spinal cord and", "modulating activity there", "•", "Summary: SNS vs PSNS:", "▪", "(Summary slide)"] }, ], ss: [ { heading: "Overview", id: "overview", items: ["Special Senses Physiology"] }, { heading: "Lecture 1 recording 1: Somatic Sensation and Sensory Receptors", id: "lecture-1-recording-1--somatic-sensation-and-sensory-recepto", items: ["", "Somatic Sensation:", "", "Sensory system: sensory receptors receive stimuli from the external or internal", "environment which is then carried by neural pathways to the brain or spinal cord;", "different parts of the brain process the information", "", "Somatosensory system: part of the sensory system concerned with the conscious", "perception of touch, pressure, pain, temperature, position, movement, and vibration,", "which arise from the muscles, joints, skin, and fascia", "", "Somatic sensation: defined as sensation from the skin, muscles, bones, tendons and", "joints which is initiated by a series of different types of sensory receptors collectively", "known as somatic receptors", "o Somatic means “relating to the body”", "o Receptors exist for each stimulus type: touch and pressure, sense of posture", "and movement, temperature, and pain", " Stimulus modality is defined as one aspect of a stimulus or what we", "perceive after a stimulus; particular form of sensory perception", " Examples of sensory modalities include: light, sound,", "temperature, taste, pressure, and smell", " Within a given modality there may also be a number of", "submodalities", "", "Somatosensation: refers to the process that conveys information regarding the body", "surface and its interaction with the environment", "o Within the parent modality of somatosensation, there are a number of", "submodalities: touch, pressure, temperature and pain", "", "Proprioception or kinesthesia: sense of posture and movement; a sensation of the", "position of your different body parts and muscle contraction in space", "o Proprioception is different from somatosensation", "o Individuals who have lost their proprioception have no brain injury and no spinal", "cord injury; there is a loss of sensory nerves and the sensation of touch;", "individuals can move their limbs, but they cannot control them in a precise way", "o Receptors responsible for proprioception are a mix of joint tendon stretch", "receptors", "", "Sensory Receptors:", "", "Each different modality has its own specialized sensory receptor", "", "Modality: a particular form of sensory perception", "o The specialized receptor cells generate graded potentials called receptor", "potentials in response to a stimulus", " Graded potentials are not action potentials, but are small", "depolarizations; if there are enough of these small depolarizations, they", "can end up generating an action potential", " Different stimulus types or modalities are sensed by different sensory", "receptors; the different modalities each have a specialized receptor", " Photoreceptors: respond to light", " Mechanoreceptors: respond to pressure", " Thermoreceptors: respond to temperature", " Auditory receptors: respond to sound", "o Sensory receptors are specific to the stimulus that they respond to, but if you", "have a really strong stimulus, not a normal stimulus, you may activate a given", "receptor, which responds in its own way", "", "Touch and Pressure Receptors:", "", "5 different types of somatosensory receptors:", "o Meissner’s corpuscles → mechanoreceptors that respond to touch and pressure", "o Merkel’s corpuscle → mechanoreceptor that responds to touch and pressure", " Meissner’s and Merkel’s corpuscles adapt to the touch and pressure", "stimulus in different manners", " Meissner’s corpuscles → rapidly adapting mechanoreceptors", " Merkel’s corpuscles → slowly adapting mechanoreceptors", "o Free neuron ending → close to the skin surface", " Include nociceptors (sense pain), thermoreceptors (sense temperature),", "mechanoreceptors (sense touch/pressure); slowly adapting", "mechanoreceptor", "o Pacinian corpuscle → responds to vibration and deep pressure; rapidly adapting", "mechanoreceptor", "o Ruffini corpuscle → responds to skin stretch; a slowly adapting", "mechanoreceptor", "", "How Are Afferents Activated?:", "", "How are the mechanoreceptors, or the somatosensory receptors, activated?", "", "The Meissner’s or Merkel’s corpuscles are somatosensory receptors that are activated", "by touch or pressure (mechanoreceptors)", "o When you poke your arm with your finger, a mechanoreceptor will be activated.", "In the distal end of the sensory receptor, there are cationic channels which", "typically allow sodium to move down its concentration gradient. These sodium", "channels open and sodium flows down its concentration gradient into the", "afferent neuron, or into the sensory receptor, and this results in a graded", "depolarization of the sensory receptor.", "", "Types of Sensory Receptors:", "", "There are 2 types of sensory receptors:", "1. The sensory receptor is located directly on the afferent fiber", " The sensory receptor is located on the afferent neuron and the afferent", "neuron travels, in the case of poking your arm, to the spinal cord (part", "of the CNS)", " Na+ flows into the cell resulting in a graded depolarization; an action", "potential is not necessarily generated but the equivalent of an", "excitatory postsynaptic potential, or an EPSP, is generated in the distal", "end of the receptor cell, which is located on the afferent", "2. The sensory receptor is located on a specialized receptor cell", " A poke in the arm activates mechanoreceptors which respond to the", "poke; cation channels open, which allow Na+ to flow into the cell,", "resulting in a graded depolarization of the receptor cell;", "neurotransmitter is then released from the receptor cell and binds to its", "receptor on the afferent neuron; the afferent neuron will take the", "information back to the spinal cord (part of the CNS)", "", "When you are poked in the arm, Na+ channels are typically activated", "o Na+ is allowed to flow into the cell, down its concentration gradient resulting in", "a graded depolarization", "", "Activation of a sensory receptor by poking your arm generated graded potentials, not", "action potentials", "o Graded potentials are the equivalent of EPSPs and are small, longer lasting", "depolarizations at the location of the sensory receptor in the periphery"] }, { heading: "Lecture 1 recording 2: The Receptor Potential and Adaptation", id: "lecture-1-recording-2--the-receptor-potential-and-adaptation", items: ["", "The Receptor Potential:", "", "This figure shows a receptor located directly on the afferent neuron; the stimulus is a", "poke in the arm", "", "In a myelinated neuron there are Nodes of Ranvier which contain voltage-gated Na+", "channels", "", "Vesicles containing neurotransmitter are found in the axon terminal; when", "neurotransmitter is released, it is released into the spinal cord onto a projection neuron", "which takes the information up to the brain", "", "A stimulus (a poke in the arm) generates a receptor potential (a graded potential)", "o With a very weak poke in the arm, a receptor potential is generated; however,", "at the first node of Ranvier (which has voltage-gated Na+ channels), there is not", "enough graded depolarization to bring the afferent neuron to threshold and", "generate an action potential; neurotransmitter is not released", " A very light touch generates only a very small depolarization which is", "not enough to bring the mechanoreceptor to threshold and generate an", "action potential; neurotransmitter is not released", "o As the stimulus intensity increases (or as the strength of the poke increases), the", "receptor potential (a graded potential) increases", " If the membrane potential at the first node of Ranvier is recorded", "(again, Node of Ranvier has voltage-gated Na+ channels) following a", "harder poke, there is enough graded depolarization to bring the afferent", "neuron to threshold, open the voltage-gated Na+ channels and fire an", "action potential; the action potentials travel down the afferent neuron", "via the process of saltatory conduction and electrotonic conduction (as", "the axon is myelinated) to the axon terminal; a certain amount of", "neurotransmitter is released; projection neurons which travel up to the", "cortex are activated and we are aware that we are being poked", "o With the hardest poke of the arm the stimulus intensity increases even more; a", "larger graded potential is generated; more action potentials are fired at the first", "Node of Ranvier (seen by the increased number of spikes); more action", "potentials are fired because the potential remains above threshold for the", "opening of the voltage-gated sodium channels the entire time; as more action", "potentials are transmitted down the axon, more neurotransmitter is released;", "the projection neuron and the cortical neurons would be activated more", "aggressively, firing more often and you are aware that you are getting poked", "quite hard in the arm", "", "Stimulus Intensity:", "", "What determines the stimulus intensity?", "o As stimulus intensity increases, more action potentials are generated at the axon", "terminal of the afferent neuron", "o Most sensory receptors do not have a single ending but have multiple sensory endings", "that, as in the case of mechanoreceptors which sense touch and pressure, are located in", "the skin", " The afferent fiber ends in a number of receptor terminals", "o In this figure, the skin is being poked by a glass probe with differing intensities; as the", "intensity of the stimulation increases, multiple receptor terminals are activated (not just", "one); activation of multiple receptor terminals is another factor which increases the", "number of action potentials that are generated by the afferent neuron", "", "As you poke the skin harder and harder, more of the receptor terminals are activated; with", "the hardest skin poke, all four receptor terminals in the afferent neuron are activated", "o The graded depolarization travels back to the first node of Ranvier; as the graded", "potential becomes greater as the skin poke becomes harder, more action potentials are", "generated in the afferent neuron", "", "As the intensity of stimulation is increased, there is more of a graded depolarization of the", "afferent, whether it is by a single receptor terminal or by a number of receptor terminals;", "with more graded depolarizations more action potentials fire in the afferent neuron, and", "this lets you know that the stimulation, in this case poking with the glass probe, is becoming", "more intense and you will be able to sense this", "", "Touch and Pressure Receptors:", "", "Different types of somatic receptors are located in the tip of the finger", "", "Multiple receptors function in the same role but differ only in the speed with which they", "adapt to a stimulus", "", "Meissner’s corpuscles and Merkel’s corpuscles", "o Both are mechanoreceptors and respond to touch and pressure", " Meissner’s corpuscle → rapidly adapting to touch and pressure", " Merkel’s corpuscle → slowly adapting to touch and pressure", "", "Adaptation:", "", "What is the relevance of the speed with which the mechanoreceptors respond to touch", "and pressure?", "o Both of the rapidly adapting receptor and the slowly adapting receptor receive", "the exact same stimulus", " A slowly adapting receptor and a rapidly adapting receptor respond", "differently to the exact same stimulus", "o We begin with no stimulation and then have an arm poke (a stimulus) which is", "held for a certain amount of time before the arm poke is taken away", " Merkel’s corpuscle → slowly adapting receptor", " Following the arm poke, a receptor potential is generated in the", "Merkel’s receptor; it decays slightly but it remains on during the", "entire time that the stimulus or the arm poke is occurring; when", "the arm poke is taken away, the receptor potential in the", "Merkel’s receptor ends and it returns back to baseline", " A large number of action potentials are generated in the", "Merkel’s receptor when the stimulus is turned on; the", "frequency of the action potentials decreases over time, but", "action potentials are still generated the entire time that the", "stimulus is on; when the stimulus is turned off, the action", "potentials stop", " Meissner’s corpuscle → rapidly adapting receptor", " When a rapidly adapting receptor is activated by an arm poke, it", "immediately generates a receptor potential with the initial", "stimulus; the receptor potential then quickly decays back to", "baseline", " Another receptor potential is generated when the stimulus", "turns off", " A short train of action potentials is generated that “matches up”", "with the receptor potential when the stimulus is turned on; a", "short train of action potentials is generated that “matches up”", "with the receptor potential when the stimulus is turned off", " During the time between when the stimulus is turned on and", "when the stimulus is turned off, no action potentials are", "generated in the rapidly adapting Meissner’s corpuscle", "", "Why not have all receptors as slowly adapting receptors?", "o Much of the information on touch that we receive is not relevant on a minute-", "by-minute basis", "o Rapidly adapting mechanoreceptors filter the unimportant information out:", " They tell you when you sit in a chair and when you get up from the", "chair, but do not continually provide information during the time you", "are sitting", " They tell you when you put a shirt on and when you take it off, but do", "not continually provide information all day that you are wearing a shirt", "o Proprioception is the ability to sense the position of your body in space and is an", "example of a slowly adapting receptor", " Information on body position in space needs to be constantly sent back", "to the CNS; to stand with your arms straight out from your body,", "constant feedback on the position of your arms from proprioceptors is", "required, which are constantly active while your arms are straight out", "from your body"] }, { heading: "Lecture 1 recording 3: Localizing the Site of a Stimulus", id: "lecture-1-recording-3--localizing-the-site-of-a-stimulus", items: ["", "Stimulus Localization:", "", "Different mechanisms are responsible for, or improve, stimulus localization so that we", "have the ability to localize where a stimulus is coming from", "o 3 important factors that affect our ability to localize a stimulus are: the", "receptive field size, the density of innervations, and overlapping receptive fields", " Receptive field size is the extent of the body which senses the poke", " Density of innervations refers to the number of sensory receptors", "within a certain area of the skin, in the case of touch", " Multiple receptive fields exist, and these receptive fields overlap with", "one another", "", "Receptive field:", "o Different sensory neurons have different receptive field sizes", "o Each sensory neuron takes information back to the CNS.", " In the case of the arm, the CNS is the spinal cord. The sensory neuron", "synapses onto a projection neuron and that projection neuron travels", "up to the brain and synapses onto a cortical neuron", " When we are poked in a given receptive field, a specific cortical neuron", "is activated", " A smaller receptive field allows for better localization of the specific site", "of stimulation", "", "Density of innervations:", "o The more densely packed the sensory receptors are, the greater the ability to", "localize the stimulus", " Certain parts of our body are very sensitive, as they are very densely", "packed with sensory neurons, or mechanoreceptors", " Lips have very densely packed sensory receptors, each with a", "fairly small receptive field, very close to one another", " Back has sensory receptors with very large receptive fields fairly", "far apart from one another", " When the lips are poked with forceps, the two tips of the", "forceps are a centimeter apart, and this activates two different", "sensory receptors; this will activate two different projection", "neurons which travel to the cortex and signal that there are two", "different stimuli on the lips", " If the skin on our back is poked by the 2 tips of a forceps, only", "one sensory neuron is activated as there is a large receptive", "field and the sensory neurons are located far apart; only one", "sensory neuron is activated and we are unable to identify that", "we are being poked with two different tips of the forceps", "", "Overlapping Receptive Fields:", "o Helps localize the site of a stimulus", "o Poking the arm with the glass probe in the middle of receptive field B activates", "all of the receptive field of sensory neuron B; part of the receptive field of", "sensory neuron A and part of the receptive field of sensory neuron C is also", "activated", "o A poke in the middle of the receptive field of sensory neuron B, generates many", "action potentials, or a very fast frequency of action potentials are generated; a", "relatively low frequency of action potentials are generated in sensory neuron A", "and sensory neuron C", "o As the frequency of action potentials generated in sensory neurons A and C is", "very similar (this is seen by a similar height of the bars in the graph), this tells", "indicates that the same number of sensory endings of sensory neuron A and", "sensory neuron C are activated and the stimulus is therefore close to the middle", "of sensory neuron B", "o If the stimulus was moved towards neuron A, fewer action potentials would be", "seen in sensory neuron B, more action potentials in sensory neuron A and", "fewer, if any, action potentials in sensory neuron C", "o If the stimulus was moved towards neuron C, fewer action potentials would be", "seen in B, more action potentials in sensory neuron C and few, if any, action", "potentials in A", "o Overlapping receptive fields allows the brain to compute the specific site of the", "stimulus based on the relative activation of different sensory neurons with", "overlapping receptive fields", "", "Lateral Inhibition:", "", "Lateral inhibition is related to overlapping receptive fields and helps identify the specific", "site of a stimulus", "o Occurs when there are overlapping receptive fields", "o Occurs in certain sensory systems such as somatosensation and vision; not", "important in the auditory system", "o Involves inhibitory interneurons", "o Lateral inhibition amplifies the signal from the neuron which is being directly", "stimulated", "o Information from afferent neurons whose receptors are at the edge of the", "stimulus is strongly inhibited compared to information from the stimulus centre", "o Lateral inhibition enhances the contrast between the centre and the periphery", "of the stimulated region, increasing the brain’s ability to localize the sensory", "input", " Localization is possible because lateral inhibition removes information", "from the peripheral regions", "", "Lateral Inhibition:", "", "Lateral inhibition amplifies the stimulated neuron and reduces the surrounding neurons,", "helping the brain to decipher the specific neuron which is being activated", "", "In the process of lateral inhibition, the postsynaptic neuron is activated when the", "central sensory neuron B is stimulated; in addition, inhibitory interneurons are also", "activated which release an inhibitory neurotransmitter (glycine or GABA) onto sensory", "neuron A and sensory neuron C, reducing the amount of action potentials that are", "generated in the projection neurons", "", "The process of lateral inhibition amplifies the difference between activation of neuron B", "and neurons A and C; this helps the brain realize that it is neuron B that is being", "activated, and not neurons A or C and B is where the stimulus, or the glass probe, is", "being poked", "", "Neurons A and C will also provide lateral inhibition onto the projection neuron of", "neuron B", "", "All of the projection neurons are turned down a little but because we have so much", "more activity in neuron B, we have a lot of inhibition in neurons A and C, and because", "neurons A and C are firing so little to start with, there is relatively little inhibition of", "neuron B", "o The inhibition of the surrounding sensory neurons, A and C, is much greater", "than the neuron that is actually stimulated, sensory neuron B"] }, { heading: "Lecture 2 recording 4: Central Control and the Somatosensory Cortex", id: "lecture-2-recording-4--central-control-and-the-somatosensory", items: ["", "Central Control of Somatosensory Information:", "", "Sensory signals are subject to extensive modification before they reach higher levels of", "the CNS", "", "Modification can come from inhibition from collaterals from other ascending neurons", "(ie. lateral inhibition), pathways descending from higher centers in the brain, by", "synapses on the axon terminals of the primary afferent neurons (an example of", "presynaptic inhibition) or indirectly via interneurons that affect other neurons in the", "sensory pathways", "o The cortex plays a role in the control of afferent information; the cortex", "provides inhibition to the sensory fibers and the projection neurons which are", "travelling up to the brain and “turns down” the volume on these neurons and", "inhibits them, reducing the effect of a stimulus", " Removal of the inhibitory effect of the cortex will result in amplification", "of your response to a given sensory input.", "o Lateral inhibition is one of the multiple ways that sensory information can be", "gated by the CNS", "", "In the pain pathways, the afferent input is continuously inhibited to some degree; this", "allows either removing the inhibition (allowing a greater degree of signal transmission)", "or increasing the inhibition (blocking the signal more completely)", "", "Central Control of Afferent Information:", "", "This figure shows a sensory neuron; different branches of the sensory receptor are", "located in the skin; this is a nociceptor or, a sensory receptor that is activated by a", "painful stimulus", "o The afferent neuron travels to the spinal cord and synapses with a projection", "neuron which travels to higher brain centers, such as the cortex", "o This figure shows inhibition of the sensory neuron and the projection neuron", "o 2 descending excitatory neurons from the cortex synapse onto the inhibitory", "interneurons", " The inhibitory neurons release inhibitory neurotransmitters onto the", "projection neurons or onto the sensory afferent neuron, reducing the", "amount of glutamate that is released onto the projection neuron by the", "sensory afferent neuron or by reducing the effect of the glutamate by", "inhibiting the projection neuron", " Remember, every cell in the CNS receives 10,000 to 40,000 synapses", "from other cells, some of them excitatory and some of them inhibitory", " The inhibitory inputs “turn down” the response of the projection", "neuron to a given stimulus", "o We want to have a esponse to a painful stimulation, but at any given time there", "is some sort of a gating going on of the painful or sensory stimulation that is", "going to vary based on the situation", "", "Neural Pathways of the Somatosensory System:", "", "All the information from the periphery travels to the somatosensory cortex via a", "projection neuron", "o Different types of information ascend to the cortex by different pathways:", " Anterolateral system (spinothalamic tract): pathway which carries pain,", "or hot/cold information up to the somatosensory cortex", " Dorsal column system: pathway which carries information on fine touch", "mechanoreception to the somatosensory cortex", "", "Anterolateral system/spinothalamic tract", "o Exposure to a painful stimulus activates free neuron endings (sensory receptors", "that respond to pain)", " Painful stimulus to the right arm activates free neuron endings in right", "arm → generation of action potentials which travel up the mixed", "peripheral nerve → first synapse between the sensory receptor neuron", "and a second neuron occurs in the dorsal horn of the grey matter of the", "spinal cord on the same side of the body which was stimulated →", "second neuron crosses the spinal cord to the other side immediately", "and then travels up the left side of the spinal cord → synapses in the", "thalamus with a cortically projecting neuron that takes information to", "the somatosensory cortex", " First synapse is located in the dorsal horn of the grey matter of", "spinal cord on same side of body which was stimulated", " Secondary neuron crosses over to the other side of the CNS at", "the level of the spinal cord", " Secondary neuron synapses with projection neuron in the", "thalamus which travels to somatosensory cortex", " Painful information crosses immediately and travels up the", "contralateral, or opposite, side of the body", "", "Dorsal column system", "o A tap on the should activates mechanoreceptors", " A tap on the right shoulder generates action potentials in", "mechanoreceptors in the right shoulder → a sensory neuron enters the", "spinal cord through the dorsal root into the dorsal horn of the grey", "matter of the spinal cord, on the same side as the stimulation →", "sensory neuron ascends up to the brainstem on the same side of the", "body as the stimulation (right side) → sensory neuron synapses with a", "secondary neuron in the brainstem → secondary neuron crosses over to", "the other side of the CNS at the level of the brainstem → secondary", "neuron synapses with a projection neuron in the thalamus which travels", "to the somatosensory cortex", " First synapse between the sensory neuron and the secondary neuron is", "in the brainstem", " Secondary neuron crosses over to the other side of the CNS at the level", "of the brainstem", " Secondary neuron synapses with projection neuron in the thalamus", "which travels to somatosensory cortex", " Touch information travels up the spinal cord on the same side of the", "body as the stimulation", "", "Both pathways end in the somatosensory cortex on the contralateral side of the body", "o One pathway crosses right away (anterolateral system) and the other one", "ascends on the same side as the stimulus and then crosses at the level of the", "brainstem (dorsal column system)", "", "The Somatosensory Cortex:", "", "Somatosensory system information is taken to the somatosensory cortex", "", "All sensory information (ie. pain or fine touch) goes from the thalamus to the", "somatosensory cortex", "", "The somatosensory cortex is located behind the motor cortex and the central sulcus", "", "Somatosensory cortex neurons activate motor cortex neurons, which control", "movement; motor cortex neurons travel down the spinal cord by descending systems to", "motor neurons, or efferent neurons, and activate them based on how we want to move", "", "The somatosensory cortex is the main region in which somatic (somatic = relating to the", "body) information is processed", "", "Each region in the body maps to a very specific region in the somatosensory cortex", "o Different regions of the body are represented by regions in the somatosensory", "cortex of different size", "o The amount of room they take up in the somatosensory cortex is determined by", "how densely innervated they are with sensory receptors", " Fingers, thumb and face are most densely innervated and are", "represented by the largest areas of the somatosensory cortex", " Lips have very small sensory receptors very densely packed", "together and take up a large part of the somatosensory cortex", " The neck, the trunk and the hips have few sensory receptors", "and take up a small region of the somatosensory cortex", "", "The smaller and more densely packed the sensory receptors are, the larger the region in", "the somatosensory cortex that they will occupy as there are more projection neurons", "taking information up to the brain"] }, { heading: "Lecture 2 recording 5: Vision and the Anatomy of the Eye", id: "lecture-2-recording-5--vision-and-the-anatomy-of-the-eye", items: ["", "Vision:", "", "Photoreceptors in the eye, or the sensory cells, are depolarized at rest and", "hyperpolarized when activated", "", "Eyes are composed of an optical component and a neural component", "o Optical component → responsible for focusing the visual image on the receptor", "cells; the front part of the eye", "o Neural component → the back part of the eye where the photoreceptors are", "located; transforms the visual image into a pattern of graded potentials and", "action potentials", "", "Visible Light:", "", "When we look at an object we are seeing light that is reflected off the object and it is", "hitting the photoreceptors of our eyes", "", "(You do not need to now the wavelengths of visible light)", "", "Anatomy of the Human Eye:", "", "Sclera → the white part of the eye; the membrane surrounding the eyeball", "", "Extraocular muscle → attached to the sclera; responsible for eye movements, such as", "looking up, down or side to side", "", "Cornea → where the sclera becomes clear at the very front, or the anterior surface, of", "the eye; responsible for refracting light waves", "o Light waves come towards the eye and refract, or bend in a little, and converge", "right at the region where the photoreceptors are located", "", "Pupil → the hole that allows light to pass through into the back of the eye", "", "Iris → regulates the size of the pupil and amount of light entering eyeball; gives your", "eyes colour", "o Innervated by the autonomic nervous system", " Parasympathetic innervation causes pupil to constrict, while", "sympathetic innervation causes pupil to dilate", "o Lens → behind the iris; works with the cornea to focus the visual image on the", "retina; the shape and size of the lens can change", "", "Cornea → static; light passes through the cornea and refracts a certain amount", "", "Zonular fibers → attached to the lens; attached to ciliary muscles", "", "Ciliary muscles → can contract/relax; change the shape of the lens", "o When objects are really close to the eye, the lens is going to change shape and", "allow you to focus that image, the visual image, on the retina of your eye, at the", "photoreceptors", "", "Retina → located behind the lens, against back of the eye; where the photoreceptors", "are found", "o Photoreceptors → rods and the cones", " Rods → activated in very low light conditions and are monochromatic", " Cones → activated when there is more light present and are responsible", "for colour vision", "", "Retinal ganglion cells → activated by the rods and the cones; take information back", "towards the brain", "", "Optic nerve → leaves through the back of the eyeball towards the thalamus and the", "cortex; made of axons of retinal ganglion cells", "", "Aqueous humour → a gelatinous fluid that fills the space between the lens and the", "cornea", "", "Vitreous humor → a gelatinous fluid found behind the lens"] }, { heading: "Lecture 2 recording 6: The Optics of Vision", id: "lecture-2-recording-6--the-optics-of-vision", items: ["", "The Optics of Vision:", "", "What is refraction? (Refraction = change in direction ie. Bending)", "o When light travels from a less dense medium into a more dense medium, the", "light waves will bend when they hit the more dense medium", "o In the eye, light travels from a less dense medium, the air, to a more dense", "medium, the eyeball, which is filled with the various gelatinous-like substances", "o Light waves travel towards the eye ball and once they hit the cornea, (a denser", "medium) they bend", "o The amount of refraction must be appropriate as there is a reconstruction of", "this arrow upside down on the retina; if the refraction is too much or too little,", "the arrow is reconstructed either in front of the retina or behind the retina and", "it is not focused", "o The cornea is primarily responsible for refraction and the lens will change shape", "to focus the image on the retina of the eye", "", "Ciliary Muscles:", "", "Lens → important for focusing the visual image on the retina", "", "Iris → the aperture that regulates the amount of light that passes into the eyeball", "o Size of pupil is regulated by the iris", "", "Lens is connected to the ciliary muscle by zonular fibers", "", "When images come very close to the eyes, the refraction that is provided by the cornea", "is insufficient to reconstruct the visual image onto the back of the retina; the image is", "instead reconstructed behind the retina, and will be out of focus", "", "When an object comes very close to the eye, the ciliary muscle contracts which causes", "the lens to get fatter and shorter and increases the amount of refraction, allowing the", "visual image to focus on the back of the retina", "", "Ciliary Muscles:", "", "When an image hits the cornea, the image is reconstructed on the retina", "", "When the image is very close, the refraction at the cornea may be insufficient to allow", "the image to be reconstructed on the back of the retina", "", "Contraction of the ciliary muscles causes the lens to go from a fairly flat, oval shape to", "fairly fat spherical shape which increases the amount of refraction or the bending of the", "light as it travels towards the back of the eye; the image is reconstructed on the retina", "and we can see it in focus", "", "Accommodation → the process of using the ciliary muscles in the lens in order to focus", "on objects that are very close; lose the ability to accommodate at around 45 years of", "age due to the breakdown of the ciliary muscles which can no longer control the lens", "", "“Ðefects” in Vision:", "", "Presbyopia → loss of elasticity of the lens resulting in the inability to accommodate for", "near vision; due to the breakdown of the ciliary muscles; age-related", "", " Myopia → nearsightedness", "o Can focus on objects up close but not far away", "o The eyeball is too long and too much refraction occurs at the level of the lens in", "order to focus the visual image on the back of the retina; the visual image is", "reconstructed at a point in front of the retina and out-of-focus", "o Corrected for by wearing glasses or contact lenses with a concave shape to", "them to reduce the amount of refraction in order to focus the visual image on", "the retina", "o Corrected for by laser surgery", "", "Hyperopia → farsightedness", "o Can focus on objects far away but not up close", "o The eyeball is too short and he visual image is reconstructed behind the retina", "as there is not enough refraction in the cornea", "o Corrected for either by glasses or contact lens with a convex lens to increase the", "amount of refraction to cause the visual image to reach a point on the retina", "o Corrected for by laser surgery for hyperopia", "", "Astigmatism → oblong shape of the eyeball is the problem", "o Corrected for with glasses or with complex laser surgery", "", "Glaucoma → damage to the photoreceptors due to increased intraocular pressure", "o Buildup of aqueous humour which pushes back on the lens; the lens in turn", "pushes back on the vitreous humour which, in turn, pushes back on the retina", "and the photoreceptors, damaging them", "o No successful treatment and anyone with glaucoma will get damage to the", "photoreceptors in the retina and the prognosis is not good for keeping vision", "long term", "", "Cataracts → clouding of the lens", "o Age-related", "o Cells of the lens die and debris builds up within them causing a graying of the", "lens and the inability to see clearly", "o Treated by taking out the lens and putting in a silicone lens or a fake lens", " A fake lens will not be able to accommodate"] }, { heading: "Lecture 2 recording 7: The Retina and Phototransduction", id: "lecture-2-recording-7--the-retina-and-phototransduction", items: ["", "Organization of the Retina:", "", "Photoreceptors → rods and cones", "o Rods → responsible for seeing objects in low light conditions", "o Cones → active in relatively brightly lit conditions and are responsible for colour", "vision", "", "Rods and the cones are connected to three different types of interneurons: horizontal,", "bipolar and Amacrine cells", "o The interneurons take information from the photoreceptors and transfer the", "information to retinal ganglion cells", "o The axons of retinal ganglion cells make up the optic nerve and take information", "to the cortex", "o Bipolar cells → interneurons which take information from the photoreceptors", "to the retinal ganglion cells", "", " Phototransduction:", "", "How are the photoreceptors activated by light?", "o Cones:", " Synaptic terminals make contact with bipolar cells", " Cones have a cell body and an inner segment and an outer segment", " The outer segment contains the disks, which are little flaps or", "layers of membrane where the actual processing of visual", "information occurs", " When light is not present (dark environment):", " An enzyme called guanylyl cyclase converts GTP", "(guanosine triphosphate) into cyclic GMP (cGMP; cyclic", "guanosine monophosphate)", " Present in the membrane of the photoreceptor is a", "cyclic GMP-gated cation channel (ligand-gated ion", "channel); the ligand which activates it is cGMP", " cGMP binds to its receptor on the cation channel; the", "cation channel opens, allowing sodium and calcium to", "flow into the cell", " The photoreceptor depolarizes as the positively charged", "ions (sodium and calcium) enter the cell", " Photoreceptors are unique- when no light is present,", "the photoreceptors are relatively depolarized", " When light is present:", " The disk of the cones contains a photopigment which", "contains a chromophore called retinal", " When light hits the photopigment, retinal changes", "conformation from cis to trans conformation; this", "change in conformation activates a molecule called", "cyclic GMP phosphodiesterase", " Cyclic GMP phosphodiesterase is an enzyme which", "breaks down cGMP; cGMP phosphodiesterase", "transforms c GMP into GMP", " The enzyme removes cGMP", "", "cGMP is responsible for opening thr cation", "channel allowing sodium and calcium to enter", "the cell", " cGMP is removed from the ion channel and the ion", "channel then closes", " Sodium and calcium can no longer enter the cell and the", "photoreceptor is therefore relatively hyperpolarized", "when light is present", "", "Remember: The photoreceptor is relatively depolarized (-35mV) when it is at rest, or", "when light is absent; the photoreceptor is relatively hyperpolarized (-75mV) when light", "is present, or in response to a stimulus", "", "Phototransduction:", "", "Retinal ganglion cells take information from the retina back towards the cortex", "", "Activation of a single cone activates two bipolar cells and two retinal ganglion cells", "", "At all times, the photoreceptor is giving information via the retinal ganglion cell that", "says “yes, light is hitting me” or, “no, light is not hitting me” via two pathways:", "o OFF pathway:", " “No, I do not have any light hitting me”", " No light → relative depolarization of the photoreceptor (-35mV)", " Graded potentials are generated in the photoreceptor and result in", "glutamate release from this photoreceptor", " Glutamate has an effect on two different cells: the ON bipolar cell and", "the OFF bipolar cell", " Important: OFF bipolar cell is activated by glutamate and the ON", "bipolar cell is inhibited by glutamate", " No light present → relative depolarization of the cone cell because of", "the cGMP → cGMP binds to its receptor on the cation channel → cation", "channel opens → sodium and calcium to flow into the cell depolarizing", "the cell → glutamate is released from the photoreceptor → glutamate", "release activates the OFF bipolar cell, resulting in the release of a lot of", "glutamate onto the OFF retinal ganglion cell → action potential is", "generated in the OFF retinal ganglion cell → action potential to the", "cortex", " No light present → glutamate released from the photoreceptor inhibits", "the ON bipolar cell → very little glutamate is released from the ON", "bipolar cell to the ON retinal ganglion cell → no action potential is", "generated in the ON retinal ganglion cell", " No light present: action potentials generated in the OFF pathway but", "not in the ON pathway", " Graded potentials are generated in the photoreceptor and bipolar cells", " Bipolar cells do not have voltage-gated sodium channels", " Action potentials can be generated in the retinal ganglion cell", " Retinal ganglion cells have voltage-gated sodium channels", "o ON pathway:", " “Yes, I have light hitting me”", " Light present → relative hyperpolarization of the photoreceptor →", "cGMP in the cone cell is broken down by cGMP phosphodiesterase →", "→ relatively little glutamate is released from the photoreceptor → very", "little glutamate is released and it does not activate the OFF pathway", "because the OFF bipolar cell is activated by glutamate → reduced", "glutamate release causes the ON bipolar cell to be released from the", "inhibition which is generated by glutamate being present → ON bipolar", "cell is activated and graded potentials are generated → glutamate", "release from the ON bipolar cell activates the ON retinal ganglion cell →", "action potential is generated in the retinal ganglion cell and travels", "down its axon towards the lateral geniculate nucleus", " Light present: ON pathway is activated due to the release of the", "inhibition on the ON bipolar cell by glutamate"] }, { heading: "Lecture 3 recording 8: Neural Pathways of Vision", id: "lecture-3-recording-8--neural-pathways-of-vision", items: ["", "Effect of Light on ON/OFF Pathways:", "", "In both the ON and OFF pathways, the photoreceptor is depolarized in the absence of", "light", "", "When light strikes the photoreceptor cell, the photoreceptor cell hyperpolarizes:", "o cGMP in the photoreceptor is broken down by cGMP-dependent", "phosphodiesterase, decreasing cytoplasmic concentrations of cGMP and", "allowing cation channels to close → cell hyperpolarizes → when photoreceptor", "cell is hyperpolarized, the cell decreases its release of glutamate", "o ON pathway: when glutamate release from the photoreceptor cell is decreased,", "the glutamate inhibition onto the bipolar cell is decreased →bipolar cell", "depolarizes and releases more glutamate→ ganglion cell depolarizes and", "generates action potentials", "o OFF pathway: there is reduced excitation of the OFF bipolar cell, as glutamate", "release from the photoreceptor has decreased →bipolar cell hyperpolarizes and", "releases less glutamate → ganglion cell hyperpolarizes and generates fewer", "action potentials", "", "Neural Pathways of Vision:", "", "The light signals are converted into action potentials through the interaction of the", "photoreceptors with bipolar cells and ganglion cells", "", "Photoreceptor cells and bipolar cells:", "o Undergo graded responses", "o Lack voltage-gated sodium channels needed to generate an action potential", "", "Ganglion cells:", "o Have voltage-gated sodium channels", "o First cells in the pathway where action potentials can be initiated", "", "Photoreceptors interact with bipolar and ganglion cells in two distinct ways or", "pathways, designated the ON pathway and the OFF pathway", "", "In both pathways, the photoreceptors are depolarized in the absence of light, causing", "the release of the neurotransmitter glutamate onto the bipolar cells", "", "Neural Pathways of Vision:", "", "Light striking the photoreceptors of both the ON pathway and the OFF pathway", "hyperpolarizes the photoreceptor cells, resulting in a decrease in glutamate release onto", "the bipolar cells", "", "Presence of light reduces the cGMP through activation of cGMP-dependent", "phosphodiesterase, allowing cation channels to close, hyperpolarizing the cell", "", "Hyperpolarization of the photoreceptor cells reduces the release of glutamate onto the", "bipolar cells", "", "Key differences between the ON and OFF pathway:", "o Bipolar cells of the ON pathway spontaneously depolarize in the absence of", "input, while bipolar cells of the OFF pathway hyperpolarize in the absence of", "input", "", "Glutamate receptors of ON pathway bipolar cells are inhibitory, while glutamate", "receptors of OFF pathway bipolar cells are excitatory", "", "Neural Pathways of Vision:", "", "When glutamate is released onto ON pathway bipolar cells, it binds to metabotropic", "receptors that cause the breakdown of cGMP → hyperpolarizes the bipolar cell,", "preventing the release of glutamate onto the ganglion cells", "", "In the absence of light: photoreceptor cell is depolarized, as cGMP binds to cation", "channels, allowing sodium and calcium to enter the cell → photoreceptor cell is", "depolarized and releases glutamate onto the bipolar cell → glutamate is inhibitory to", "the bipolar cell in the ON pathway (ON bipolar cell) which hyperpolarizes, decreasing its", "release of glutamate onto the ganglion cells → ganglion cells of the ON pathway (ON", "ganglion cell) are not stimulated and do not generate action potentials in the absence of", "light", "", "Presence of light: photoreceptor cell is hyperpolarized as cGMP is broken down by", "cGMP-dependent phosphodiesterase, removing cGMP from binding to and opening", "cation channels → reduced release of glutamate from the photoreceptor cells removes", "the inhibition on the ON bipolar cells which release glutamate onto the ganglion cells", "causing them to generate action potentials", "", "Neural Pathways of Vision:", "", "OFF pathway bipolar cells have ionotropic glutamate receptors that are nonselective", "cation channels → glutamate binds to glutamate receptors on the bipolar cells, the", "channel opens, depolarizing the cell → depolarization of the bipolar cells stimulates", "glutamate release onto the ganglion cells → generation of action potentials in the", "ganglion cells", "", "OFF pathway generates action potentials in the absence of light (no action potentials in", "the presence of light)", "", "Coexistence of the ON and OFF pathways in each region of the retina improves image", "resolution by increasing the brain’s ability to perceive contrast at edges or borders", "", "Visual Pathways and Fields:", "", "Visual cortex → in the occipital lobe", "", "Left eye", "o Information from the lateral half of the field of view hits the nasal region of the", "retina travels via the axons of the retinal ganglion cells back towards the optic", "chiasm → information from the nasal retina crosses to the contralateral, or", "opposite, side of the cortex at the optic chiasm → synapses in the lateral", "geniculate nucleus → neurons from the lateral geniculate nucleus take the", "information to the visual cortex.", "o Information from the medial half of the field of view →temporal region of the", "retina → travels to the optic chiasm but does not cross at the optic chiasm →", "stays on the same (ipsilateral) side → ipsilateral lateral geniculate nucleus", "where there is a synapse → information travels to the visual cortex in the", "occipital lobe", "", "Visual information from each eye goes both to the same side of the brain and also the", "contralateral side of the brain", "", "Information from the lateral field of view → nasal region of the retina → crosses to the", "contralateral side at the optic chiasm → lateral geniculate nucleus → visual cortex", "", " Information from the medial field of view → temporal part of the retina → travels on", "the same side, or ipsilateral side, of the body to the lateral geniculate nucleus → visual", "cortex"] }, { heading: "Lecture 3 recording 9: Hearing and Sound", id: "lecture-3-recording-9--hearing-and-sound", items: ["", "Hearing:", "", "Pinna → the physical or external ear that resides outside the head", "", "Temporal lobe → contains the auditory cortex", "", "Sound energy is transmitted through different media: gaseous, liquid, or solid, by setting", "up a vibration of the medium’s molecule; air is the most common medium in which we", "hear sound energy", "", "Hearing: Sound:", "", "The tuning fork is surrounded by air molecules", "o Striking the tuning fork causes it to wiggle back and forth and a noise of a", "certain pitch is heard, depending on specifically where the tuning fork is hit", "o Hitting the tuning fork moves air molecules surrounding the tuning fork such", "that you get zones of compression", " Zones of compression are regions where air molecules are tightly", "packed or close together", " Zones of rarefaction are regions where there are relatively few air", "molecules", " Zones of compression and rarefaction ripple outward, transmitting the", "sound wave over distance", "o Amplitude (the volume or loudness of the music):", " Determined by how many air molecules are located within one of the", "zones of compression or the difference between the pressure of", "molecules in the zones of compression and rarefaction", "o Frequency (pitch):", " Determined by the distance between the zones of compression, or the", "number of zones of compression or rarefaction in a given time", " The faster the vibration, the higher the pitch", "o Anything capable of disturbing molecules can serve as a sound source", "o We hear things when the zones of compression and rarefaction hit the ear"] }, { heading: "Lecture 3 recording 10: The Anatomy of the Ear and Sound Transmission", id: "lecture-3-recording-10--the-anatomy-of-the-ear-and-sound-tra", items: ["", "Anatomy of the Human Ear:", "", "Pinna (earlobe) → the physical or external ear that resides outside the head", "", "The outer ear and the external auditory canal funnel the zones of compression and", "rarefaction in toward the middle and inner ear", "", "Air molecules, found in the zones of compression and rarefaction, travel along the", "external auditory canal and hit the tympanic membrane (ear drum)", "", "Tympanic membrane → outer ear; vibrates in and out as air molecules push against it", "o Moves in and out at an amplitude and frequency consistent with the features of", "the sound that you are listening to", "o If you are listening to a stereo, the tympanic membrane will be moving in and", "out; when you turn up the volume on the stereo, the displacement will be", "greater at the higher volume", "o If the frequency of the sound is increased, the tympanic membrane will move", "more quickly and if the frequency of the sound is decreased, it will move more", "slowly", "", "Anatomy of the Middle Ear and Cochlea:", "", "Cochlea → inner ear", "", "Tympanic membrane is attached to three bones located in the middle ear:", "o Malleus, incus and stapes", " Tympanic membrane → malleus → incus → stapes", " Bones act as levers and amplify the sound", " The small movements of the tympanic membrane that occur in", "response to the movement of the air molecules are amplified by", "the malleus, the incus and the stapes", " Why is amplification needed?", " The outer ear and the middle ear are both filled with air", "and the inner ear (where the sensory receptors for the", "auditory system are located) is filled with fluid", " The vibrations pass from air to fluid", "", "Skeletal muscles are attached to malleus and stapes which can contract to dampen", "movement of the bones and reduce impact on the inner ear in response to loud sounds", "o Malleus → tensor tympani muscle", "o Stapes → stapedius muscle", "o Muscles contract to protect ear from consistent, ongoing loud sounds; muscles", "would not protect the ear from a really loud sudden bang as they would not be", "contracted when the sudden loud noise occurred", "", "Stapes is basically a foot and terminates on the inner ear, a region known as the oval", "window", "o Oval window of the inner ear or the cochlea", "o The foot pushes against the oval window and the cochlea (the inner ear) is full", "of fluid; foot pushes fluid forward within the inner ear", "", "Tympanic membrane moves → 3 bones amplify the movement, with the stapes pushing", "against the inner ear and causing movement of fluid within the inner ear", "", "Anatomy of the Human Ear:", "", "When sound becomes too loud, the stapedius muscle and the tensor tympani muscles", "contract and dampen the movements of the bone", "", "Sound Transmission in the Ear:", "", "Cochlea:", "o Inner ear", "o Divided into 3 compartments: scala vestibuli (top), scala tympani(bottom) and", "cochlear duct (middle)", " Scala vestibuli → has fluid called perilymph", " Scala tympani is → has fluid called perilymph", " Cochlear duct → has fluid called endolymph; region of inner ear where", "the sensory receptors for the auditory system are located", "", "Sound waves coming through the external auditory canal → move tympanic membrane", "→ moves the bones of the middle ear → stapes pushes against the oval window →", "causes movement of the perilymph towards the end of the cochlear duct (helicotrema)", "→ also causes movement of the perilymph down across the cochlear duct moving from", "scala vestibuli towards scala tympani", "o Movement of fluid down from scala vestibule to scala tympani results in", "activation of the sensory receptors for the auditory system (found in the", "cochlear duct)", "", "Cochlea & the Organ of Corti:", "", "3 compartments of the cochlea (inner ear): scala vestibuli, scala tympani and cochlear", "duct", "", "Cochlear duct: where the sensory receptors for the auditory system are located", "o Sensory receptors for the auditory system are known as hair cells", " Hair cells are located in the cochlear duct on a structure known as the", "Organ of Corti: a specialized sensory epithelium that allows for the", "transduction of sound vibrations into neural signals", " Hair cells have stereocilia protruding from them at their tips", " 2 anatomically separate groups of hair cells; a single row of inner hair", "cells and three rows of outer hair cells", " The stereocilia of the single row of inner hair cells extend into", "the endolymph and transduce pressure waves caused by fluid", "movement in the cochlear duct into receptor potentials", " The stereocilia of the 3 rows of outer hair cells are attached to", "the tectorial membrane", " At the bottom, each outer hair cell is attached to the", "basilar membrane", " Different regions of the basilar membrane vibrate", "maximally at different frequencies", "", "The hair cells in the region of peak vibration of", "the basilar membrane undergo the most", "mechanical deformation; this information is", "sent to the CNS, which interprets the pattern of", "hair cell stimulation as a sound of a particular", "frequency", "", "Different sound frequencies are detected along", "the length of the Organ of Corti", "", "Vestibulocochlear nerve → takes auditory information from the ear towards the brain", "o Tympanic membrane vibrates based on the characteristics of the sound →", "activates the malleus, incus and stapes in the middle ear → pushes against the", "oval window and amplifies the movements → pushes the perilymph down", "across the cochlear duct → when fluid is pushed down, the basilar membrane", "moves up and down based on the amplitude and the frequency of the sounds", "→ the hair cells move back and forth", "", "Hair Cells of the Organ of Corti:", "", "The hair cells move back and forth when the basilar membrane moves", "o Remember, the stereocilia of the outer hair cells are attached to the tectorial", "membrane at the top", "o When the stereocilia move, a mechanically-gated potassium channel opens", " This is how the auditory receptors are activated and how they", "depolarize", " When the basilar membrane moves, the hair cells move back and forth", "and the stereocilia bend", " When the stereocilia are bent towards the tallest member of a", "bundle, mechanically-gated cation channels open, allowing", "potassium to flow down its concentration gradient through the", "channel", " In the ear, there is little potassium in a hair cell as", "opposed to the extracellular space", " When the mechanically-gated potassium channel is", "opened, potassium flows down its concentration", "gradient into the cell", " Once potassium has flowed into the cell, the hair cell", "depolarizes due to the inward movement of positively", "charged potassium", " This generates graded potentials in the hair cell", " The neurotransmitter glutamate is released onto the", "afferent neurons", " The afferent neurons make up the vestibulocochlear", "nerve", " If enough glutamate is released to bring the afferent", "neurons to threshold, action potentials are generated in", "the vestibulocochlear nerve and travel back towards the", "brain", " Bending of the hair cells in the opposite direction closes", "the channels, allowing the cell to rapidly repolarize", " As sound waves vibrate the basilar membrane, the", "stereocilia are bent back and forth, and the membrane", "potential of the hair cell rapidly oscillates, leading to", "bursts of neurotransmitter being released onto afferent", "neurons"] }, { heading: "Lecture 3 recording 11: More on Hearing", id: "lecture-3-recording-11--more-on-hearing", items: ["", "Neural Pathways in Hearing:", "", "Cochlear nerve fibers synapse with interneurons in the brainstem", "o From the brainstem information is transmitted by a multineuron pathway to the", "thalamus and then to the auditory cortex in the temporal lobe", "", "Restoration of Hearing:", "", "Restoration of hearing: hearing aids and cochlear implants", "o Hearing aids:", " Auditory machinery in the ear is not as sensitive", " An amplifier which is placed in the auditory canal which activates the", "existing auditory machinery", " Amplifies existing sounds", " Hearing aids are restricted to the outer ear component and can be", "turned up and down in volume", "o Cochlear implant:", " People have damage to certain components of the outer, middle or", "inner ear", " Machinery of the ear simply does not work", " A speaker put on the outside of the head which picks up noises and", "transduces them into electrical impulses", " Electrodes go from the speaker down to the vestibulocochlear nerve", "and send electrical impulses to the vestibulocochlear nerve dependent", "on the features of the sound that the receiver is picking up", " The receiver is on the outside of the head; takes in auditory", "information and bypasses the outer, middle, and inner ear; directly", "electrically stimulates the vestibulocochlear nerve to take information", "from the vestibulocochlear nerve to the cortex which accurately", "represents the features of the sound"] }, ], cardio: [ { heading: "Overview", id: "overview", items: ["Cardiovascular Physiology", "***Make sure you know the equations from the cardiovascular lectures. Important equations to know", "are list right below. These equations will help you answer questions on the exam! You will not need a", "calculator for the exams.", "Eg. CO = HR x SV. You may be asked what happens to CO if you increase HR? If HR increases (and SV", "remains the same), CO will increase.", "Important equations to know:", "F= ∆P/R", "R = 8 L η/ π r4", "EF (ejection fraction) = SV/EDV", "SV = EDV - ESV", "CO = HR x SV", "MAP = CO x TPR", "PP = SP – DP (pulse pressure = systolic pressure – diastolic pressure)"] }, { heading: "Lecture 1 recording 1: Hemodynamics", id: "lecture-1-recording-1--hemodynamics", items: ["", "Why Do We Have a Cardiovascular System?:", "", "To provide oxygen and nutrients and remove wastes like carbon dioxide from cells", "", "Rapid system", "", "Provides a steep concentration gradient within the vicinity of every cell…very important", "in multicellular organisms as diffusion is too slow a process", "", "Hemodynamics:", "", "The study of blood flow and relates Ohm’s law to fluid flow, looking at the relationship", "between blood flow, blood pressure, and resistance to blood flow", "", "F = ∆P/R", "o F = flow", "o ∆P = pressure difference between two fixed points (P1 and P2)", "o R = resistance to flow", "o Blood flow is related to the pressure difference between the two fixed points", "and inversely proportional to the resistance", "o Resistance is defined as the friction that impedes flow, or how difficult it is for", "blood to move between 2 points at any given pressure", "", "Blood always flows from a region of higher pressure to a region of lower pressure", "o The pressure difference between 2 points provides the driving force for blood", "flow", "o To have flow, the pressure difference must overcome resistance to flow (∆P > R)", "", "Our bodies can change factors that affect blood flow: by changing resistance blood flow", "can be altered", "o The major mechanism for changing blood flow is to alter the resistance of blood", "vessels, in particular arterioles", "", "The figures in this slide show: it is not the absolute pressures in the cardiovascular", "system that determine flow, but the pressure difference between two points", "o The pressures in the two tubes are very different, but the pressure differences", "are the same", "", "Hydrostatic pressure → blood hydrostatic pressure is the pressure that the volume of", "blood within our circulatory system exerts on the walls of the blood vessels that contain", "it", "o Often called ‘pressure’ and it varies throughout the cardiovascular system", "", "Hemodynamics:", "", "It is not the absolute pressure at any point in the cardiovascular system that determines", "flow rate but the difference in pressure between two relevant points", "o There must be a pressure difference to create flow; if there is no pressure", "difference, the flow will be 0 mL/min", " The pressure difference must be greater than the sum of all resistances", "to create flow", "", "What Determines the Resistance to Blood Flow?", "", "Resistance can be calculated numerically from the formula F=delta P/R, but it cannot be", "measured as it is determined by several factors", "o Factors that determine resistance to blood flow: viscosity of the blood, length of", "the blood vessel, and diameter of the blood vessel", "", "Viscosity → the friction between molecules of a flowing fluid", "o Blood contains many molecules and the formed elements in blood (red blood", "cells, white blood cells, and platelets). Interaction between different", "components in blood produces friction which contributes to resistance to blood", "flow.", " Hematocrit, or the number of red blood cells in the blood, affects", "viscosity", "", "Blood vessel length and diameter affect the amount of vessel wall that the blood is in", "contact with", "o Friction develops between the moving blood and the stationary vessel walls", "o The greater the contact between the vessel walls and the blood, the greater the", "friction produced and the greater the resistance to flow", "o A vessel with a longer length will produce more friction than a shorter vessel", "o Vessel diameter can change by constriction or dilation of the vessel", " Constriction of the vessel will reduce the diameter of the vessel while", "dilation of the vessel will increase the vessel diameter", " Blood flows through vessels in concentric layers", " In smaller diameter vessels, more blood is in contact with the vessel", "wall, as there are less concentric layers of blood flowing through the", "smaller vessel; this generates more friction as the blood moves through", "the vessel", " In larger diameter vessels, some blood will be in contact with the vessel", "walls, but many of the layers will move through the vessel without", "contacting the vessel wall; friction in the larger diameter vessel will be", "less than that produced in the smaller diameter vessel", "", "The relationship between viscosity, vessel radius, and vessel length is defined by", "Poiseuille’s equation:", "o Resistance (R) is equal to 8 times eta times L divided by pi times r raised to the", "fourth power", " R = 8 L η/ π r4", " R = the resistance to blood flow, η =the blood viscosity, L = the vessel", "length and r= the inside radius of the vessel", " Resistance to flow is directly proportional to the length of the vessel and", "the blood viscosity and inversely proportional to the radius of the vessel", " The factor with the greatest effect on resistance is the diameter or the", "radius of the vessel as r is raised to the 4th power", " Very small changes in vessel diameter therefore lead to large changes in", "resistance; our bodies are able to alter vessel diameter by constricting", "and relaxing vascular smooth muscle in the wall of the blood vessels and", "change the resistance to blood flow in our bodies"] }, { heading: "Lecture 1 recording 2: Cardiovascular System Functions and Components", id: "lecture-1-recording-2--cardiovascular-system-functions-and-c", items: ["", "Functions of the Cardiovascular System:", "", "To deliver oxygen and nutrients and remove waste products of metabolism", "", "Fast chemical signaling to cells by circulating hormones or neurotransmitters", "", "Thermoregulation", "", "Mediation of inflammatory and host defense responses against invading", "microorganisms", "", "Components of the Cardiovascular System:", "", "Heart, blood vessels and blood", "", "Components of the Cardiovascular System:", "", "Vessels: arteries, arterioles, capillaries, venules and veins", "", "Arterioles → small branching vessels with high resistance", "", "Capillaries → transport of blood between small arteries and veins; exchange of", "materials between blood and cells in the body", "", "All arteries carry blood away from the heart", "", "All veins carry blood back to the heart", "", "Closed circulatory system allows for greater pressures to be generated when the heart", "contracts", "", "Anatomy of the Heart:", "", "Heart has 4 chambers: 2 atria and 2 ventricles", "", "Atria:", "o Thin-walled chambers", "o Low pressure chambers", "o Receive blood returning back to the heart", "", "Ventricles:", "o Thick-walled chambers (thicker than atria)", "o Responsible for the forward propulsion of blood when they contract", "", "Apex of heart is the lowest superficial surface of the heart", "", "Base of heart is the upper surface of the heart where the blood vessels attach", "", "Septa:", "", "Left and right sides of the heart are divided by septa, or muscular walls", "o Interatrial septum → separates left and right atria", "o Interventricular septum → separates left and right ventricles", "o Allows heart to function as a dual pump", " Left side pumps highly oxygenated blood to systemic circuit (body)", " Right side pumps poorly oxygenated blood to pulmonary circuit (lungs)"] }, { heading: "Lecture 1 recording 3: Blood Flow", id: "lecture-1-recording-3--blood-flow", items: ["", "Blood Flow:", "", "The circulatory system can be divided into two serial circuits: the pulmonary circulation", "and the systemic circulation", "o Pulmonary circuit → carries blood to and from the gas exchange surfaces of the", "lungs; blood entering the lungs is poorly oxygenated; once blood enters the", "lungs, oxygen diffuses from the lung tissues to the blood; blood leaving the", "lungs is highly oxygenated", "o Systemic circuit → transports blood to and from the rest of the body; blood", "entering the body tissues is highly oxygenated; oxygen diffuses from the blood", "to the interstitial fluid surrounding the tissue cells; blood leaving the tissues is", "poorly oxygenated", "", "Serial means in sequence", "", "Path of Blood Flow:", "", "Systemic circuit → moves blood to and from the tissues in the body", "", "The left side of the heart receives blood from the pulmonary circulation and pumps it to", "the systemic circulation", "", "The right side of the heart receives blood from the systemic circulation and pumps it to", "the pulmonary circulation", "Right", "ventricle", "Pulmonary", "trunk/artery", "Pulmonary", "vein", "Lungs", "Right", "atrium", "Body", "cells/tissues", "Vena", "cava", "Aorta", "Left", "atrium", "Left", "ventricle", "Poorly", "oxygenated", "blood", "Highly", "oxygenated", "blood", "Highly", "oxygenated", "blood", "Pulmonary Circulation", "Systemic Circulation", "Pulmonary", "valve", "Left AV", "valve", "Aortic", "valve", "Right AV", "valve", "", "Blood moves from the pulmonary circuit to the heart and then to the systemic circuit", "before returning back to the heart: it moves in series", "", "Arteries → carry blood away from heart; most carry highly oxygenated blood except", "pulmonary trunk and pulmonary arteries which carry poorly oxygenated blood to lungs", "", "Veins → carry blood to the heart; most carry poorly oxygenated blood back to the heart", "except pulmonary venules and pulmonary veins which carry highly oxygenated blood", "back to the left atrium from the lungs", "", "Series vs Parallel Flow:", "", "Series blood flow found in cardiovascular system", "o Pulmonary and systemic circuits", "", "Parallel flow to most organs", "o This means that each organ is supplied by a different artery and therefore its", "blood flow can be independently regulated", " An exception is the liver – it receives blood flow in parallel and in series", "(will talk about in GIT section)", "", "Distribution of Blood Flow at Rest and During Exercise", "", "Cardiovascular system can not only increase the rate of blood flow, but it can also alter", "the distribution of our blood flow, depending on the needs of your body, increasing", "blood flow to areas that need more blood and decreasing blood flow to areas that do", "not need as much blood at that time"] }, { heading: "Lecture 1 recording 4: The Pericardium", id: "lecture-1-recording-4--the-pericardium", items: ["", "Functions of the Pericardium:", "", "Pericardium → a fibrous sac surrounding the heart and the roots of the great blood", "vessels leading into and out of the heart", "o Functions:", " Stabilizes the heart in the thoracic cavity", " Provides protection to the heart by physically surrounding it", " Reduces friction as the heart beats by secreting the pericardial fluid", " Limits overfilling of the heart chambers", "", "The Pericardial Structure:", "", "3 layered sac: fibrous pericardium, parietal pericardium and visceral pericardium", "o Fibrous pericardium → outer layer of the pericardial sac; provides protection for", "the heart and stabilizes the heart in the thoracic cavity by attaching to", "structures in the chest; holds the heart in place; limited distensibility which", "prevents the sudden, rapid overfilling of the heart", "o Parietal pericardium → part of the serous pericardium; lies underneath the", "fibrous pericardium and is attached to it", "o Visceral pericardium → part of the serous pericardium; innermost layer of the", "pericardial sac, and is also called the epicardium when it comes into contact", "with the heart muscle;", "o Pericardial cavity → separates the parietal pericardium from the visceral", "pericardium; both parietal and visceral pericardium secrete fluid which", "decreases friction between pericardial membranes as heart beats", "o Serous layer → a layer composed of cells that secrete a fluid", "", "The Pericardial Structure:", "(Another view of the pericardium)", "", "Cardiac Tamponade:", "", "Pericarditis → an inflammation of the pericardium caused by viruses, bacteria, fungi,", "trauma or malignancy; leads to fluid accumulation in the pericardial cavity", "", "Cardiac tamponade → compression of heart chambers due to excessive accumulation of", "pericardial fluid; heart's movement is limited and heart chambers cannot fill with", "adequate amount of blood (ie. a decrease in ventricular filling)"] }, { heading: "Lecture 1 recording 5: The Heart Wall and Cardiac Muscle Cells", id: "lecture-1-recording-5--the-heart-wall-and-cardiac-muscle-cel", items: ["", "Ventricular Walls:", "", "The muscular wall of the left ventricle is thicker than the right ventricle", "o The increased thickness allows the left ventricle to generate higher pressures as", "it contracts compared to the right ventricle, allowing it to pump blood around", "the entire systemic circulatory system", "o Right ventricle only needs to pump blood to the lungs and does not need to", "develop pressures as great as those developed by the left ventricle", "", "The Heart Wall:", "", "Heart wall has 3 layers: epicardium, myocardium and endocardium", "o Epicardium → also called visceral pericardium", " Layer immediately outside the heart muscle and covers the outer", "surface of the heart; connective tissue attaches it to the myocardium;", "functions as a protective layer for the heart", "o Myocardium → the muscular wall of the heart and lies underneath the", "epicardium", " Contains muscle cells or myocytes which contract and relax as the heart", "beats", " Contains nerves and blood vessels", "o Endocardium → innermost layer of the heart wall", " Lines heart cavities and the heart valves; a thin layer of endothelium", "which is continuous with the endothelium of the attached blood vessels", "", "The entire circulatory system (heart chambers, heart valves and blood vessels) is lined", "by endothelium which forms an interface between the blood and the heart chamber or", "blood vessel wall, providing a smooth surface for blood to flow over", "", "3 layers (endocardium, myocardium, and epicardium) are found in both atria and both", "ventricles", "o The layers do show variation between the different chambers of the heart", " The ventricles have a thicker myocardium than the atria; the left", "ventricle has a thicker myocardium than the right ventricle", "", "Cardiac Muscle Cells:", "", "Myocytes = cardiac muscle cells", "o Branched or Y shaped cells", "o Joined longitudinally or end to end to adjacent myocytes", " Allows for greater connectivity in the heart,", "o Striated or stripped appearance (Actin and myosin)", "o A single centrally located nucleus", "o Rich in mitochondria (Provide ATP for the muscle cells to contract)", "o Adjacent cells are held together by intercalated disk", " The membranes of 2 different myocytes are closely opposed and very", "intertwined at their region of attachment", " 2 types of specialized intercellular junctions at intercalated", "disks: desmosomes and gap junctions", "", "Desmosomes:", "", "Adhering junctions that hold cells together in tissues subject to considerable mechanical", "stress or stretching.", "", "Mechanically couple one heart cell to another", "", "Proteins involved: cadherins, plaques, intermediate filaments", "o Cadherins from one cell attach to cadherins from another cell", "", "Gap Junctions:", "", "Communicating junctions", "", "Electrically couple heart cells, allowing ions to move between cells", "o Important for spread of action potential", "", "Proteins involved: connexons", "", "Arrangement of the Heart Muscles:", "", "Muscle fibers are arranged spirally around the heart chambers", "", "Important for emptying blood into arteries when ventricles contract"] }, { heading: "Lecture 2 recording 6: The Heart Valves", id: "lecture-2-recording-6--the-heart-valves", items: ["", "The Four Valves of the Heart:", "", "There are 4 heart valves:", "o Atrioventricular (AV) valves → found between the atria and the ventricles on", "both the left and right sides of the heart.", " AV valve located between the left atrium and left ventricle is the", "bicuspid or mitral valve", " AV valve located between the right atrium and the right ventricle is the", "tricuspid valve.", "o Semilunar (arterial) valves → found between the ventricles and the arteries into", "which the ventricles pump their blood", " Valve between the left ventricle and the aorta is the aortic valve", " Valve between the right ventricle and the pulmonary trunk is the", "pulmonary valve", "", "Valves:", "o Made of fibrous tissue (collagen) covered by endothelium", "o The valve flaps are also called leaflets or cusps", "", "Valve rings:", "o Made of cartilage", "o These are what the valves attach to", "", "The Valves and the Path of Blood Flow:", "(This slide shows the position of the heart valves in the circulatory circuit)", "", "How do the Valves Function?:", "", "Function of the heart valves?", "o Ensure unidirectional flow of blood through the heart", " Important so that blood flowing out of heart does not mix with new", "blood coming into the heart", "", "The valves open and close passively due to differences in pressure or pressure gradients", "o Energy is not expended to open or close a valve", "o Valves do not require muscles to open or close them", "o A forward pressure gradient opens a one way valve; a backwards pressure", "gradient closes a one-way valve", "o Valves normally do not open in the opposite direction", "", "Atrioventricular (AV) Valves:", "", "Found between the atrium and the ventricle", "", "Prevent the backflow of blood into the atrium when the ventricle contracts", "", "When the pressure in the atrium exceeds the pressure in the ventricle, the", "atrioventricular valve will open, allowing blood to flow from the atrium into the", "ventricle so that the ventricle will fill with blood", "", "When the ventricle contracts and achieves a pressure greater than the pressure in the", "atrium, the valve will shut, preventing the backflow of blood from the ventricle into the", "atrium", "", "Tricuspid valve → Av valve located between the right atrium and the right ventricle;", "consists of three cusps or leaflets attached at the circumference to the valve rings", "", "Bicuspid or mitral valve → AV valve located between the left atrium and the left", "ventricle; consists of two cusps or leaflets attached at the circumference to the valve", "rings", "", "Each AV valve is part of an AV valve apparatus, which consists of the cusps or leaflets of", "the valve, chordae tendineae and papillary muscles", "", "Anatomy of the AV Valve Apparatus:", "", "Atrioventricular valve apparatus:", "o The edges of the AV valve leaflets are attached to tough, thin fibrous cords of", "tendinous-type tissue called chordae tendineae", "o The chordae tendineae extend from the edges of the leaflets and attach to", "papillary muscles", "o Papillary muscles → cone shaped muscles that protrude from the inner surface", "of the ventricular walls", " Papillary muscles do contract, and when they contract they pull on the", "chordae tendineae to become tight (taut)", " This holds the valve in its closed position", "", "Function of the AV Valve Apparatus:", "", "Heart valves open and close passively due to pressure gradients; there are no muscles", "involved in opening and closing the valve", "", "When the left ventricle is relaxed:", "o AV or bicuspid valve is open and the semilunar or aortic valve is closed", "o Papillary muscles are also relaxed and chordae tendineae are slack or have low", "tension", "o When the bicuspid valve is open, blood can flow from the left atrium into the", "left ventricle; the ventricle fills with blood as the aortic valve is closed; blood", "enters the ventricle but cannot leave", "", "When left ventricle has begun to contract:", "o The ventricle will squeeze its volume of blood as it contracts, increasing", "pressure inside the ventricle", "o As the pressure in the ventricle rises above the pressure in the atrium, blood is", "pushed back towards the bicuspid valve; but the increased pressure causes the", "bicuspid valve to close as there is a greater pressure in front of this valve", "o Closing of the bicuspid valve prevents the backflow of blood into the atrium as", "the ventricle is continuing to contract", "o The papillary muscles also contract when the ventricle contracts", " This pulls the chordae tendineae downward or taut; chordae tendineae", "have tension", " Pulling of the chordae tendineae by the papillary muscles keeps the AV", "valve in a closed position in the face of a strong backward pressure", "gradient from the ventricle contracting", " The AV valve apparatus keeps the AV valves from everting, or opening", "backwards, into the atrium", " If the AV valves did evert, blood would flow the wrong way from", "the ventricle to the atrium", "", "Important: contraction of the papillary muscles does not open or close the valves; the", "valves open and close passively due to pressure differences across the valves", "", "As the pressure in the ventricle continues to increase as the ventricle continues to", "contract, the pressure in the ventricle will eventually exceed the pressure in the aorta,", "opening the aortic valve, allowing blood to flow out of the ventricle; this is a forward", "pressure gradient", "", "Arterial (Semilunar) Valves:", "", "Semilunar or arterial valves:", "o Found between the ventricle and the artery into which the ventricle ejects its", "blood", "o 3 leaflets or cusps (left and right semilunar valves)", " Pulmonary valve → valve found between the right ventricle and the", "pulmonary trunk", " Aortic valve → valve found between the left ventricle and the aorta", "o Do not have chordae tendineae or papillary muscles (no valve apparatus", "associated with these valves)", " The pressure pushing back against the valve from the artery is not high", "enough to force the valve to evert or open backwards into the ventricle,", "as the artery does not contract", "o Open when the pressure in the ventricle is greater than that in the artery into", "which the ventricle ejects its blood", "o When the ventricle begins to relax, the pressure in the ventricle will decrease;", "when the pressure in the ventricle falls below the pressure in the artery, the", "semilunar valve will close, preventing the backflow of blood from the artery into", "the ventricle", "", "Semilunar valves open/close due to pressure differences across the valve; there are no", "muscles or energy expended to open/close these valves", "", "Pulmonary Valve:", "(This is an image of a valve)"] }, { heading: "Lecture 2 recording 7: The Heart’s Skeleton and Coronary Circulation", id: "lecture-2-recording-7--the-heart-s-skeleton-and-coronary-cir", items: ["", "Cardiac Skeleton:", "", "The fibrous skeleton of the heart:", "o Made of dense connective tissue", "o Includes the heart valve rings and the dense connective tissue between the", "heart valves", "o Functions:", " Physically separates the atria from the ventricles", " Electrically inactive and blocks the direct spread of electrical impulses", "from the atria to the ventricles", " Provides support for the heart, providing a point of attachment for the", "valves leaflets and cardiac muscle", "", "Coronary Circulation:", "", "The heart, like other organs, receives its blood supply through arteries that branch from", "the aorta", "o Coronary circulation is part of the systemic circulatory system and supplies", "blood to and provides drainage from the tissues of the heart", " Coronary arteries → arteries supplying the heart", " Aortic sinus is a dilation or out-pocketing of the ascending", "aorta; site where the left and right coronary arteries", " Cardiac veins → collect poorly oxygenated blood and empty into the", "coronary sinus, which returns blood to the right atrium", "", "Coronary Circulation:", "", "Coronary sinus → a collection of veins joined together to form a large vessel that", "collects blood from the myocardium of the heart and empties into the right atrium,", "returning the poorly oxygenated blood back to the right side of the heart", "", "Systole → represents the time during which the left and right ventricles contract and", "eject blood into their respective artery", "", "Diastole → represents the period of time when the ventricles are not contracting;", "relaxed", "", "Myocardial blood flow is not steady:", "o Blood flow almost ceases while the heart is contracted (systole) and peaks while", "the heart is relaxed (diastole)", "", "Coronary Artery Disease:", "", "Coronary artery disease:", "o Caused by atherosclerosis of the coronary arteries supplying blood to the heart", "tissues", "o Atherosclerosis is a condition in which the arteries become hardened and", "narrowed because of an excessive accumulation of plaque in the vessel wall", " Atherosclerotic plaque → made of fat, cholesterol, calcium and other", "substances in the blood", " When plaque builds up, the diameter of that artery is narrowed,", "providing resistance to blood flow, reducing flow through the arteries", "supplying the heart tissue", "", "Coronary Artery Disease:", "", "Angina → chest pain; when a plaque is present in a coronary artery, restricted blood", "flow to the heart muscle may result in or chest pain.", "", "Myocardial infarction → heart attack; atherosclerotic plaques can grow so large that", "they completely block arterial blood flow, causing a heart attack; heart muscle dies due", "to loss of blood supply"] }, { heading: "Lecture 2 recording 8: Cardiac Muscle and Membrane Potential", id: "lecture-2-recording-8--cardiac-muscle-and-membrane-potential", items: ["", "The Cardiac Syncytium:", "", "Cardiac muscle cells = myocytes", "o Joined by intercalated discs which contain gap junctions and desmosomes", " Mechanically, chemically, and electrically connect myocytes to one", "another", " The entire heart tissue resembles a single, enormous muscle cell", "and the cardiac muscle is called a syncytium (a set of cells that", "act together)", "", "Gap junctions allow excitation, or action potentials, to spread quickly from one myocyte", "to another by cell-to-cell contact", "o Cardiac muscle cells are so tightly connected that when one of the myocytes", "becomes excited, the action potential spreads to all of them through gap", "junctions", " The heart is a functional syncytium:", " Cardiac muscle has 2 syncytia: the left and right atria act as one", "functional syncytia and the left and right ventricles also act as", "another functional syncytia", " This gives the heart an all or none property- either all of the", "myocytes respond and are excited or none of the myocytes", "respond", "", "Cardiac Muscle:", "", "The heart contracts in series: first the left and right atria contract together and then the", "left and right ventricles contract together", "", "Action potentials lead to contraction of heart muscle cells and ejection of blood", "", "Autorhythmicity (automaticity) → the heart contracts or beats rhythmically as a result", "of action potentials that it generates itself", "o Action potentials in the heart are generated without nervous or hormonal", "stimulation", "o The rhythmicity of the heart is myogenic in origin, which means muscular in", "origin", "", "2 types of specialized cardiac muscle cells or myocytes: contractile cells and conducting", "cells", "o Contractile cells:", " Perform the mechanical work of pumping or contracting to propel blood", "forward; generate pressure to move blood", " ~ 99 % of myocytes are contractile cells", " Do not normally initiate their own action potentials, but contract when", "stimulated by an action potential passed to them through gap junctions", "from an adjacent contractile cell that has been stimulated by an action", "potential or an adjacent conducting cell.", "o Conducting cells:", " Autorhythmic cells which initiate and conduct action potentials which", "are responsible for contraction of the contractile cells", " Conducting cells are myocytes (muscle cells) which initiate and conduct", "action potentials without nervous or hormonal stimuli", " Have very few myofibrils (protein filaments needed for contraction) and", "do not contribute to the heart’s contraction and the movement of", "blood.", " ~ 1 % of myocytes are conducting cells", " Part of the conducting system of the heart", " Are in electrical contact with each other and the cardiac", "contractile cells through the gap junctions", "", "Membrane Potential:", "(This is a review)", "", "Membrane potential → a separation of positive and negative charges across a", "membrane or a difference in the electrical potential across a cell’s membrane (mV)", "", "Cells at rest maintain a non-zero transmembrane potential, with a negative voltage in", "the cell interior as compared to the cell exterior", "", "Membrane potential → influences the movement of ions across the membrane", "", "Action potential → when the resting membrane potential is transiently reversed from", "negative values inside the cell to values more positive than outside,", "", "In muscle cells, action potentials are the electrical events that cause the mechanical", "event of contraction", "", "The action potential is brought about by changes in the membrane permeability to", "certain ions", "", "The Action Potential:", "(This is just a review of the nerve/muscle action potential)"] }, { heading: "Lecture 2 recording 9: The Heart’s Conducting System", id: "lecture-2-recording-9--the-heart-s-conducting-system", items: ["", "Components of the Conducting System:", "", "The spread of action potentials through the myocardium leads to the contraction of the", "heart muscle cells", "", "The heart contracts in series: first both atria depolarize and contract as a unit before", "both ventricles depolarize and contract as a unit", "", "The conducting system contains myocytes, or cardiac muscle cells, that are capable of", "initiating and propagating action potentials", "o Autorhythmic myocytes", "o The conducting myocytes are found in: sinoatrial node (SAN), internodal", "pathways, atrioventricular node (AVN), the bundle of His (AV bundle), the left", "and right bundle branches, Purkinje fibers", "o SAN located in the wall of the right atrium; AVN located at the base of the right", "atrium; internodal pathways extend from the SAN to the AVN and also cross the", "interatrial septum to the left atrium; bundle of His passes through the cardiac", "skeleton; left and right bundle branches travel along the interventricular", "septum; left and right bundle branches make contact with Purkinje fibers, which", "extend into the myocardium of the ventricles", "", "Cardiac Skeleton:", "", "Non-conducting or it will not allow action potentials to travel across it", "", "Physically separates the atria from the ventricles: stimuli cannot cross from the atria to", "the ventricles through the cardiac skeleton", "o The only electrical connection between the atria and ventricles in a normal", "heart is the AVN and the Bundle of His", "", "Sinoatrial (SA) Node:", "", "All the cells in the conducting system are capable of initiating action potentials", "o The rate at which each region action potentials differs", "", "Conducting myocytes in the SAN generate action potentials at the fastest rate; 60 to", "100 action potentials per minute", "", "This stimulus is then passed on to the other regions of the conducting system through", "gap junctions, generating action potentials in these other regions before they have time", "to initiate their own action potentials", "", "SAN generates action potentials that drive the rest the conducting system.", "o Cardiac pacemaker → initiates action potentials that set the heart rate", "", "SAN generates action potentials → internodal pathways → contractile cells of both the", "left and the right atria → left and right atria contract at same time → stimulus is also", "passed by the internodal pathways to AVN → the wave of depolarization must pass", "through the AVN and the Bundle of His to excite the ventricles due to presence of", "cardiac skeleton", "", "Cells of conducting system are muscle cells", "", "Atrioventricular (AV) Node:", "", "Stimulus passes to the AVN through the internodal pathways from the SAN", "", "AV nodal delay: the propagation of action potentials through the AVN is relatively slow:", "takes ~ 100 milliseconds for the stimulus to pass through the AVN to the Bundle of His", "o This delay ensures that the atria depolarize and contract before the ventricles", "depolarize and contract", " The ventricular myocardium must be relaxed to fill with blood from the", "atria", " Ensures ventricles are relaxed and have time to fill with blood before", "they contract", "", "Excitation of the Ventricles:", "", "AVN and Bundle of His are the only electrical connection between the atria and", "ventricles in a normal heart", "", "Left and right bundle branches travel along intraventricular septum and make contact", "with Purkinje fibers", "", "Purkinje fibers", "o Large number, diffuse distribution (ie. all over the ventricles), fast conduction", "velocity", "o Stimulus depolarized left and right ventricular myocytes and causes contraction", "nearly simultaneously due to Purkinje fibers", "", "Sequence of Excitation:", "", "This slide shows the spread of excitation from the sinoatrial node to the atrioventricular", "node and the left and right atria", "", "Cells are connected by gap junctions, which offer a low resistance pathway for", "excitation to spread from cell to cell", "o Ions move from cell to cell through gap junctions", "", "Summary: Conducting System of the Heart:", "", "This figure demonstrates how the wave of depolarization spreads across the heart", "", "Myocytes in the SAN initiate the action potential; action potential passes through the", "conducting myocytes in the internodal pathways to the contractile myocytes of both the", "left and right atria causing depolarization and contraction of the atrial myocardial cells;", "action potential also passes through the conducting myocytes in the internodal", "pathways to the AVN; it takes 100 msec for the stimulus to pass through the AVN;", "stimulus passes to the conducting cells of the Bundle of His which divides into the left", "and right bundle branches; wave of depolarization spreads down the interventricular", "septum; the bundle branches separate at the apex of the heart and enter the ventricles", "and make contact with the Purkinje fibers; Purkinje fibers spread the depolarizing", "stimulus to the ventricles", "", "The chambers of the heart contract in series: first both atria depolarize and contract,", "and then both ventricles depolarize and contract, leading to the movement of blood", "through the heart", "", "Wolff-Parkinson-White Syndrome:", "", "There is an extra connection in the heart called an accessory pathway", "o An accessory pathway is an abnormal piece of muscle that connects directly", "between the atria and the ventricles", " Allows electrical signals to bypass the AVN and move from the", "atria to the ventricles faster than usual", " Electrical impulses may also be transmitted abnormally from", "the ventricles back to the atria", " Disrupts the coordinated movement of electrical signals through", "the heart, leading to an abnormally fast heartbeat, called", "tachycardia, and other arrhythmias"] }, { heading: "Lecture 3 recording 10: Action Potentials in the Heart", id: "lecture-3-recording-10--action-potentials-in-the-heart", items: [" *Know the action potentials, the phases of the action potentials and the ion channels/ions involved", "for the slow/fast action potentials in the heart", "", "Two Types of Action Potentials:", "", "Fast and slow action potentials", "o Fast: found in contractile myocytes in the atrial myocardium, ventricular", "myocardium, bundle of His, Bundle branches (left and right) and Purkinje fibers", "o Slow: found in conducting myocytes in the sinoatrial node and atrioventricular", "node", "", "The terms fast and slow describe how quickly the membrane potential changes during", "the depolarization phase of the action potential", "o Fast action potential:", " Rapid rate of depolarization in which the membrane potential rises very", "quickly from the threshold potential to the new transiently positive", "potential", "o Slow action potential:", " Slower rate of depolarization, in which the membrane potential takes", "more time to reach the new potential", "o Why do action potentials have different rates of depolarization? Depends on the", "ions and ion channels involved in the depolarization phase", "", "The Cardiac Action Potential:", "", "Phases of the cardiac action potential are associated with changes in permeability of the", "cell membrane mainly to Na+, K+, Ca2+ ions", "", "Opening and closing of ion channels alters permeability", "", "[K+]IN > [K+]OUT", "", "[Ca2+]OUT > [Ca2+]IN", "", "[Na+]OUT > [Na+]IN", "", "SA Node Action Potential:", "", "Phases of the slow action potential: pacemaker potential, depolarization and", "repolarization", "", "SAN cells:", "o Pacemaker potential → it is not a steady or true resting potential but a slow", "depolarization to threshold; gradual depolarization of the membrane potential", "to threshold", "o When threshold is reached, the depolarization phase of the action potential", "occurs", "", "Pacemaker potential allows the SAN cells (these are muscle cells) to generate regular", "spontaneous action potentials without any external influence from nerves or hormones", "", "Stages of slow action potential and ion channels involved:", "o Pacemaker potential → 3 ionic conductances involved: 1) progressive reduction", "in K+ permeability (K+ channels that opened during the repolarization phase of", "the previous action potential gradually close due to the return of the membrane", "to negative potential), 2) F-type channels (depolarizing Na+ current; Na+ moves", "into cell), 3) T-type channels (Ca2+ channel; T= transient; opens only transiently", "(briefly), contributes an inward Ca2+ current, provides a final depolarization to", "bring the membrane to threshold)", "o Depolarizing phase → L-type channels (Ca2+ channel; L= long-lasting; channels", "open more slowly and remain open for a prolonged or long period)", " The Ca2+ currents depolarize the membrane more slowly than voltage-", "gated Na+ channels so the rising phase of the action potential occurs", "much more slowly than if Na+ was responsible for the rising phase;", "action potentials are therefore called ‘slow’ action potentials", "(remember voltage-gated Na+ channels are responsible for the", "depolarization phase of the nerve/muscle action potential)", " The long opening of the L-type channels prolongs the nodal action", "potential- it is approximately 150 milliseconds in duration", "(nerve/muscle action potentials ~ 2 milliseconds)", "o Repolarization phase → opening of voltage-gated K+ channels; K+ leaves the cell", "", "SAN cells undergo repeated cycles of drifting pacemaker potential and firing of the", "action potential, allowing these cells to generate action potentials in the absence of any", "hormonal or nervous stimuli", "o Gradual depolarization of the pacemaker potential allows SAN to generate", "action potentials", "", "The slow-type action potential is also seen in the AVN", "", "Summary of Slow Action Potential:", "", "Slow type action potential: Ca2+ currents are responsible for the depolarization phase of", "the action potential and not Na+; Ca2+ moves much more slowly through its channels", "than Na+ does moving through voltage-gated Na+ channels, giving a slower", "depolarization phase", "", "Pacemaker potential → provides the SAN with automaticity (ability of the cells to", "generate action potentials independent of external nervous or hormonal stimuli)", "o The movement of ions through ion channels is responsible for the pacemaker", "potential, bringing the cell membrane to threshold where an action potential", "will fire; ion channels will open/close as cell moves through the pacemaker", "potential based only on the cell’s membrane potential, and not as the result of", "any external hormonal or nervous stimuli", "", "AVN → ‘slow type action potential’; slow pacemaker potential than SAN pacemaker", "potential", "o As the SAN pacemaker potential reaches threshold first, it will pass its stimulus", "to other cells in the heart, driving the heart rate at a rate of 60 - 100", "beats/minute", "o If SAN becomes damaged, the AVN may generate action potentials to drive the", "ventricles, but at a lower rate of ~ 40 - 60 beats/minute", "0", "0", "Membrane potential (mV)", "–50", "–100", "0.15", "0.30", "Threshold", "Na+ enters through", "F-type channels", "Depolarization phase: L-type", "channels open at threshold and Ca2+", "slowly enters cell.", "Repolarization phase: Opening of K+", "channels and closing of L-type Ca2+", "channels. K+ exits through K+ channels.", "Pacemaker potential: Closing of", "K+ channels, Na+ entering", "through F-type channels and Ca2+", "entering through T-type channels", "Begin: -60 mV.", "K+ channels begin to", "close", "Ca2+ enters through", "T-type channels", "Time (sec)", "", "Ventricular Muscle Cell Action Potential:", "", "K+ conductances involved in the resting phase, the notch and the repolarization phase", "have varying properties and involve different subsets of K+ channels; simply know that", "various K+ channels are involved", "", "Duration of the action potential is ~ 250 to 300 milliseconds, due to the long plateau", "phase", "o This affects the duration of the refractory period", "", "This fast-type action potential is also found in the atrial contractile cells (atrial", "myocardium)", "", "Comparison of Cardiac Action Potentials:", "(This is for interest only- it shows the action potentials in different regions of the heart.", "While the SAN and AVN have the same slow type action potential, which varies from", "each other; the atrial myocardium and ventricular myocardium have the fast type action", "potential, which also varies from each other)"] }, { heading: "Lecture 3 recording 11: The Electrocardiogram (ECG, EKG)", id: "lecture-3-recording-11--the-electrocardiogram--ecg--ekg-", items: ["", "The Electrocardiogram (ECG, EKG):", "", "A recording of the electrical activity of the heart", "Membrane potential (mV)", "-100", "Time (sec)", "0", "0.15", "0.30", "0", "Depolarization:", "Opening of fast", "voltage-gated Na+", "channels at", "threshold", "Repolarization:", "Opening of K+ channels", "and closing of Ca2+", "channels", "Plateau: Ca2+ entering", "through L-type channels and", "slow opening of K+ channels", "that will repolarize cell", "Notch: Due to transient", "opening of K+ channels", "Stable resting phase:", "Leak of K+ through K+", "channels", "250 - 300 msec", "Threshold", "", "A measure of the currents generated in the extracellular fluid by the changes occurring", "simultaneously in many cardiac cells", "o Can be measured by an array of electrodes placed on the body surface.", "o Electrical activity can be seen from different angles", "", "The electrical signal becomes weaker as it travels through the body tissues to the", "surface of the skin", "o Voltage changes in the heart’s ventricular muscle are ~ 100 millivolts in", "magnitude, but only 1 millivolt at the surface of the skin", "", "Used to diagnose problems with the heart’s conducting system", "", "Placement of Electrodes in the 12 Lead ECG:", "", "ECG allows different angles for viewing heart’s electrical activity", "", "An established electrode pattern results in specific tracing pattern", "o Look for differences in the established tracing patter if there are electrical", "problems in the heart", "", "ECG Recording:", "", "ECG represents changes occurring simultaneously in many cardiac cells", "o ECG is not recording changes from individual cardiac cells,", "", "P wave:", "o First wave on ECG", "o Represents depolarization of the atria", "o Upward deflection in the trace", "o Approximately 25 milliseconds after the P-wave, the atria will contract", "", "QRS complex:", "o Wave consisting of 3 peaks, labelled Q, R and S", "o Represents depolarization of the ventricles", "o When the ventricles are depolarizing, the atria repolarize", " Atrial repolarization is too small an electrical event to be recorded at", "the surface of the skin", "", "T wave:", "o Upward deflection", "o Represents repolarization of the ventricles", "", "The ECG and the Heart’s Actions Potentials:", "", "ECG → shows a 1 millivolt difference in the membrane potential recorded,", "", "Action potential → shows changes of approximately 110 millivolts", "", "Some ECGs:", "", "Many myocardial defects alter normal action potential propagation, and as a result the", "shapes and timing of the waves on the ECG vary", "", "AV node block → a type of heart block in which conduction between the atria and", "ventricles is impaired; partial or complete interruption of the impulse from the atria to", "the ventricles", "", "Normal ECG: P-wave always followed by the QRS complex and the T-wave; synchrony", "between the atria and ventricles: first the atria depolarize and then the ventricles", "depolarize", "", "Partial AV node block: the damaged AV node permits only every other atrial impulse to", "be transmitted to the ventricles; every second P-wave is not followed by a QRS complex", "or a T-wave", "", "Complete AV node block: electrical depolarizations of the atria are not transmitted to", "the ventricles; no synchrony between atrial and ventricular electrical activities", "", "Any component of the heart’s conduction system is capable of initiating action", "potentials to drive the heart", "o Different regions generate action potentials at different rates", " SAN generates action potentials at fastest rate; in a normal healthy", "heart, the SAN generates action potentials which drive the rest of the", "hearts conducting system; heart’s pacemaker"] }, { heading: "Lecture 3 recording 12: Excitation-contraction Coupling in the Heart", id: "lecture-3-recording-12--excitation-contraction-coupling-in-t", items: ["", "Cardiac Myocytes:", "", "Cardiac myocyte → muscle cell of the heart", "", "Intercalated disk → where the membranes of two adjacent myocytes are extensively", "intertwined; both desmosomes and gap junctions", "", "Sarcolemma → plasma or cell membrane of a cardiac", "", "Sarcoplasmic reticulum → a special type of smooth endoplasmic reticulum which stores", "and pumps Ca2+", "o Ca2+ is important for excitation-contraction coupling", "", "Cardiac Myocytes:", "", "Cardiac myocytes:", "o Contain myofibrils", " Myofibrils are made up of sarcomeres", " Sarcomeres → contractile unit of muscle; contain the protein", "filaments actin and myosin", " Actin → thin filament", " Myosin → thick filament", " Orderly arrangement of actin and myosin in the", "myofibrils gives cardiac muscle its striated or striped", "appearance", "o T-tubules → invaginations of the sarcolemma; surround myofibrils; transmit", "action potentials propagating along the surface membrane to the interior of the", "muscle fiber; lie in close proximity to the sarcoplasmic reticulum and contain", "many L-type Ca2+ channels", "", "Excitation-contraction Coupling (ECC) in Cardiac Muscle:", "o Excitation-contraction coupling → the process by which the arrival of an action", "potential at the cell membrane leads to contraction of the muscle cell", "o Steps involved in ECC:", " Ca2+ levels control contraction of the cardiac muscle", " Ca2+ is normally found in low concentrations in the cytoplasm of", "the cell, and high concentrations in the extracellular fluid", " During the plateau phase of the action potential, extracellular Ca2+", "enter the cytoplasm of the cardiac muscle cell through the L-type Ca2+", "channels", " This Ca2+ is not sufficient to cause contraction of the myocytes", " Ca2+ that enters through the L-type calcium channels binds to ryanodine", "receptors on the sarcoplasmic reticulum (SR)", " Ryanodine receptors bind Ca2+ and have an intrinsic Ca2+", "channel; when Ca2+ binds to the ryanodine receptor, the", "channel in the ryanodine receptor opens, allowing the release", "of Ca2+ from the SR into the cytoplasm", " SR has a high concentration of Ca2+", " Ca2+ causes its own release from the SR following binding to the", "ryanodine receptor = calcium-dependent calcium release or calcium-", "induced calcium release", " SR is the source of ~ 95% of the Ca2+ in the cytoplasm", " Ca2+ is important for contraction of the cardiac muscle cells", "", "Activation of Cross-bridge Cycling by Calcium:", "(Review of cross-bridge cycling)", "", "Troponin → contains binding sites for Ca2+ and tropomyosin, and regulates access to", "myosin-binding sites on actin", "", "Tropomyosin → partially cover the myosin-binding sites on actin at rest, preventing", "cross-bridges from making contact with actin", "", "EEC in Cardiac Muscle: Contraction:", "", "Steps involved in contraction:", "o Excitation spreads along the sarcolemma, or plasma membrane, from", "ventricular myocyte to ventricular myocyte by gap junctions", "o Excitation spreads down to the interior of the myocyte by T-tubules", "o T-tubules also contain many L-type calcium channels", "o During the plateau phase of the fast action potential, the permeability of the", "myocyte to Ca2+ increases as L-type Ca2+ channels in the sarcolemma and T-", "tubules open following a change in membrane potential", " This Ca2+ entering the myocyte binds to ryanodine receptors on the SR", "o Ryanodine receptors (Ca2+ -release channels)", " Following binding of Ca2+, the ryanodine receptors contain an intrinsic", "channel that opens to allow Ca2+ to exit the SR into the cytoplasm of the", "cell (calcium-induced calcium release)", "o Cytosolic Ca2+ binds to troponin, inducing a conformational change in the", "regulatory complex; binding sites on actin are now able to bind to the energized", "cross-bridge on the myosin head", " Cross-bridge cycling and shortening of the sarcomere and contraction of", "the muscle", "", "Release of Calcium During EEC:", "(Review of the steps involved in ECC in the heart)", "", "L-type calcium channels → voltage-gated Ca2+ channels and are a type of modified DHP", "receptor, or dihydropyridine receptor", "o We talked about these DHP receptors in our section on nerve, muscle and", "synapse. *", "", "Calcium-dependent calcium release or calcium-induced calcium release → calcium", "causes its own release from the sarcoplasmic reticulum", "", "In cardiac muscle there is no physical coupling or physical connection between the L-", "type calcium channel (which is a modified dihydropyridine receptor) and the ryanodine", "receptor", "o It is Ca2+ that enters the cell through the L-type Ca2+ channels that then moves to", "and binds to the ryanodine receptors on the sarcoplasmic reticulum membrane;", "this causes the release of Ca2+ from the sarcoplasmic reticulum (calcium-", "dependent calcium release)", "", "Excitation-contraction Coupling: A Comparison:", "", "Comparison of skeletal muscle and cardiac muscle", "", "Skeletal muscle → no calcium-dependent calcium release; instead there is a physical", "coupling of the dihydropyridine receptor, or the DHP receptor, and the ryanodine", "receptor that results in the opening of an intrinsic Ca2+ channel in the ryanodine", "receptor (We discussed this in the nerve/muscle/synapse section)", "", "Cardiac muscle → no physical coupling or physical connection between the L-type Ca2+", "channel, which is a modified dihydropyridine receptor, and the ryanodine receptor; L-", "type Ca2+ channels in the membrane open following the arrival of an action potential;", "the Ca2+ that enters the cell through the L-type Ca2+ channels moves to and binds to the", "ryanodine receptors in the SR causing the release of Ca2+ from the SR (calcium-", "dependent calcium release or calcium-induced calcium release)"] }, { heading: "Lecture 3 recording 13: Excitation-contraction Coupling in the Heart: Relaxation", id: "lecture-3-recording-13--excitation-contraction-coupling-in-t", items: ["", "ECC in Cardiac Muscle: Relaxation:", "", "Relaxation of the ventricular myocardium is important as the ventricles only fill with", "blood when they are relaxed (diastole)", "", "The interaction of myosin with actin causes cross-bridge cycling and muscle contraction;", "Ca2+ plays a role in cross bridge cycling by binding to troponin, allowing interaction", "between actin and myosin", "", "To end a contraction Ca2+ must be removed from troponin", "o Ca2+ levels in the cytoplasm must be reduced to pre-release levels. How?:", " L-type Ca2+ channels close to reduce influx of Ca2+ into the cell", " SR will no longer be stimulated to release Ca2+ into the cytoplasm as", "Ca2+ is no longer entering the cell and binding to ryanodine receptors on", "the SR", " SR contains Ca2+-ATPases to pump Ca2+ in the cytosol back into the SR", " Ca2+ is also removed from the myocyte by a Na+/Ca2+ exchanger found in", "the sarcolemma", " The reduced binding of Ca2+ to troponin will block the sites of", "interaction between myosin and actin, allowing for relaxation of the", "myofibrils", "", "Uptake of Calcium During ECC:", "", "Removal of Ca2+ from the cytosol:", "o Ca2+-ATPase on the SR – removes the majority of Ca from2+ the cytosol", "o Na+/Ca2+ exchanger found in the sarcolemma", "o (also closing of L-type Ca2+ channels as we saw in previous slide)", "", "Refractory Period:", "", "Refractory period → a period of time during and after an action potential in which an", "excitable membrane cannot be re-excited", "", "Due to the long plateau phase of the ventricular action potential, the refractory period", "lasts almost as long as the contraction", "o Absolute refractory period ~ 250 milliseconds", " The membrane will not respond to another stimulus, regardless of how", "strong it is", " Membrane of the muscle cell is refractory due to the inactivation of the", "fast voltage-gated sodium channels that open during the depolarization", "phase of the action potential", " After the voltage-dependent Na+ channels close, they enter a state of", "inactivation and cannot be opened again until the membrane of the", "muscle cell has returned back to negative potentials, where the", "channels will begin to recover and are ready to be opened again", "o The long refractory period prevents tetanus"] }, { heading: "Lecture 4 recording 14: Phases of the Cardiac Cycle", id: "lecture-4-recording-14--phases-of-the-cardiac-cycle", items: ["", "The Cardiac Cycle:", "", "The cardiac cycle can be divided into systole and diastole", "", "Systole → ventricular contraction and ejection of the blood", "", "Diastole → ventricular relaxation and filling of the ventricles with blood", "", "The cardiac cycle length is the period of time from the beginning of one heartbeat to the", "beginning of the next", "o Each heart beat involves one ventricular systole and one ventricular diastole", "o The heart spends most of the time in diastole", " The longer time spent in diastole is important for ventricular filling as", "the ventricles only fill with blood when they are relaxed", "", "Systole:", "", "Ventricular systole can be divided into two phases: isovolumetric ventricular contraction", "and ventricular ejection", "o When the ventricles contract, they squeeze the volume of blood in their", "chambers, generating pressure; pressure creates blood flow", "o Isovolumetric = ‘iso’ + ‘volumetric’; same volume (constant/unchanging volume)", " Iso = same", " Volumetric = volume", " Isovolumetric ventricular contraction → ventricles contract, all heart", "valves closed (AV and semilunar valves), blood volume in ventricles", "remains constant, pressures rise; muscle develops tension but cannot", "shorten", " Blood cannot enter or exit the ventricles because the valves are", "closed", " During isovolumetric ventricular contraction, the ventricular", "walls do develop tension as they contract and squeeze the", "blood in the chamber, raising the ventricular blood pressure.", "The blood is incompressible and cannot flow anywhere as the", "valves are closed", " Ventricular myocardium is squeezing against the incompressible", "blood and the volume is not changing; the ventricular muscle", "fibers cannot shorten", " Ventricular ejection phase → pressure generated by the ventricles", "during contraction now exceeds the pressure in the artery into which", "the ventricle ejects its blood", " This forward pressure gradient opens the semilunar valves,", "allowing the ventricular muscle fibers to shorten as the", "ventricles continue contracting and eject their volume of blood", "into the arteries", " AV valve is closed during ventricular ejection, being held in the", "closed position by the chordae tendineae and the papillary", "muscles", " Ventricular muscle fibers are shorten as the blood is ejected", "from the ventricles", "o Stroke volume → the volume of blood ejected from each ventricle during", "systole, or during contraction", " The left and right ventricles eject the same volume of blood when they", "contract, but the left ventricle does this with more pressure than the", "right ventricle", " When contracting, the ventricles do not eject their entire volume of", "blood", "", "Diastole:", "", "Ventricular diastole can be divided into two phases: isovolumetric ventricular relaxation", "and ventricular filling", "o The ventricles can only fill with blood while the ventricular myocardium, or the", "muscle layer of the ventricles, is relaxed", "o Isovolumetric ventricular relaxation → all heart valves closed, blood volume", "remains constant, pressures drop", " AV valve and semilunar valve are closed", " During isovolumetric ventricular relaxation, ventricular volume is not", "changing and the pressure inside the ventricles is dropping as the", "myocardium is relaxing", "o Ventricular filling → AV valves open, blood flows into ventricles from atria;", "ventricles receive blood passively (atria are relaxed)", " When the atria are in diastole they receive blood returning back to the", "heart in the veins; once that the atria are full of blood (and the", "ventricles are relaxed), pressure in the atria rises above the pressure in", "the ventricles (the pressure in the atria is simply due to the volume of", "blood in the atria); this is a forward pressure gradient", " The forward pressure gradient will open the AV valves, allowing blood", "to flow from the relaxed atria to the relaxed ventricles", " 2 phases of ventricular filling: passive ventricular filling and atrial", "contraction", " Passive ventricular filling → the ventricles receive", "approximately 70 per cent of their blood volume", " In passive ventricular filling both the atria and the", "ventricles are relaxed; atria have a greater pressure", "than the ventricles because they are full of blood", " Atrial contraction or atrial kick → completes ventricular filling;", "remember ventricles are still relaxed", "", "Phases of the Cardiac Cycle:", "(This slide goes over the phases of the cardiac cycle, looking at what is happening in the", "ventricles and the atria. Make sure you understand the phases of systole (isovolumetric", "ventricular contraction, ventricular ejection) and diastole (isovolumetric ventricular diastole,", "ventricular filling (passive ventricular filling and atrial contraction))", "", "Cardiac cycle → the rhythmical contraction and relaxation of the heart’s chambers", "coordinated by the electrical activity in the heart; represents the events that occur in", "the chambers of the heart during one single heart beat", "", "The same series of events occurs in both the left and right sides of the heart at the same", "time; the difference being that when the left ventricle contracts, it contracts with more", "force/pressure than the right ventricle, due to the thicker myocardium, or the thicker", "muscle layer"] }, { heading: "Lecture 4 recording 15: The Pressure-volume Curve", id: "lecture-4-recording-15--the-pressure-volume-curve", items: ["", "Pressure-volume Curve:", "", "Also called Wiggers diagram", "", "Pressure is the key to understanding blood flow patterns and the opening and closing of", "valves:", "o Pressure is generated when the muscles of the heart chamber contract as well", "as when a chamber fills with blood", "o Blood always flows from a region of higher pressure to a region of lower", "pressure", "o Valves open and close in response to a pressure gradient; a forward pressure", "gradient opens a one-way valve while a backward pressure gradient shuts a", "one-way valve", "", "Pressure-volume Curve:", "", "End-diastolic volume (EDV) → the amount or volume of blood in each ventricle at the", "end of ventricular diastole; measured in millilitres (mL)", "", "End-systolic volume (ESV) → the amount or volume of blood in each ventricle at the end", "of ventricular systole, or at the end of ventricular contraction and ejection; in mL", "", "When the ventricles contract they do not eject their entire volume of blood", "o Stroke volume (SV) → the volume of blood pumped out of each ventricle during", "systole", " Calculated as: SV = EDV - ESV", " Typical SV values for an adult at rest are ~ 70 - 75 mL"] }, { heading: "Lecture 4 recording 16: More on the Pressure-volume Curve", id: "lecture-4-recording-16--more-on-the-pressure-volume-curve", items: ["", "Pressure-volume Curve:", "(Make sure you understand the Wigger’s diagram and the events that occur. Listed below", "are some examples of questions that can be asked based on this diagram)", "", "Wigger’s diagram; shows the pressure and volume changes for the heart", "", "The same events occur simultaneously on both sides of the heart", "1", "4", "3", "2", "0", "110", "50", "130", "65", "QRS", "ECG", "Phase of cardiac cycle", "Diastole", "Systole", "Diastole", "1st", "2nd", "Pressure (mmHg)", "Left ventricular volume (mL)", "P", "T", "Aortic valve", "opens", "Aortic valve", "closes", "Left AV", "valve opens", "Left atrium and", "ventricle are", "relaxed. Aortic", "valve closed.", "Pressure in", "ventricle increases", "as ventricle", "contracts", "Passive filling", "Left AV", "valve closes", "EDV", "Isovolumetric", "ventricular", "contraction", "Ventricular", "ejection", "ESV", "Aortic pressure", "Isovolumetric", "ventricular", "relaxation", "Ventricle", "almost full", "from passive", "filling", "", "Below are 2 questions from the practice questions which show the type of question you", "may be asked based on knowledge of the pressure-volume curve:", "", "During ventricular filling:", "o The ventricles contract", "o The semilunar valves are closed", "o The atrioventricular (AV) valves are closed", "o Blood flows from the ventricles to the atria through the AV valve", "o The pressure in the ventricles decreases", "", "During ventricular ejection:", "o The AV valves are open; the semilunar valves are closed", "o The AV valves are open; the semilunar valves are open", "o The AV valves are closed; the semilunar valves are open", "o Blood flows from the atria to the ventricles", "o The ventricle empties its entire volume of blood", "", "The Right Heart:", "", "The right ventricle develops lower pressures than the left ventricle during systole", "", "Right ventricle undergoes the same series of events as the left ventricle", "", "Heart Sounds:", "", "First heart sound → lub; caused by closure of the AV valves at the beginning of", "isovolumetric ventricular contraction and signifies the onset of ventricular systole", "", "Second heart sound → dub; caused by closure of the semilunar valves and signifies the", "onset of ventricular diastole", "", "The heart sounds reflect turbulence when the valves passively snap shut as the", "pressures across the valves change", "", "The valves on the left and right sides of the heart are also closing at the same time", "o Lub and dub signify closing of the valves on both sides of the heart; both the left", "and right AV valves close together and make the sound lub and both semilunar", "valves close together and make the sound dub", "", "Heart Sounds and Murmurs:", "", "Normally blood flow through valves and vessels is laminar flow and makes no sound", "o Laminar flow is characterized by smooth concentric layers of blood moving in", "parallel down the length of a blood vessel", "o The highest velocity (Vmax) is found at the central axis, or the center, of the", "vessel and the lowest velocity (V=0) is found along the vessel wall", "o The flow profile is parabolic once laminar flow is fully developed", "o This occurs in long, straight blood vessels, under steady flow conditions", "o Under conditions of high flow, particularly in the ascending aorta, laminar flow", "can be disrupted and become turbulent", "", "Abnormal flow may be turbulent", "o Turbulent flow makes a sound and is called a murmur", "o Stenotic valve → a valve in which the leaflets do not open completely; this can", "occur when the valve leaflets become stiffer due to calcium deposits or scaring", "of the valve; when blood flows through a stenotic valve, it becomes turbulent", "and this is heard as a murmur", "o Insufficient valve → does not close completely due to widening of the aorta or", "scaring of the valve; blood flows backwards through the leaky valve and", "produces turbulence which is heard as a murmur"] }, { heading: "Lecture 4 recording 17: The ANS and Cardiac Output", id: "lecture-4-recording-17--the-ans-and-cardiac-output", items: ["", "Autonomic Innervation of the Heart:", "", "The heart is innervated by sympathetic and parasympathetic fibers", "o Sympathetic innervation through the thoracic spinal nerves", " Sympathetic postganglionic fibers innervate the entire heart, including", "the atria, ventricles, SA node and AV node", " Neurotransmitter released: norepinephrine", "o Parasympathetic innervation through the vagus nerve", " Parasympathetic postganglionic fibers innervate the atria, SA node and", "AV node", " Neurotransmitter released: acetylcholine", " Important: ventricles do not receive significant parasympathetic", "innervation and the ventricular myocardium is not affected by", "parasympathetic activity", "", "(Do not need to know the type of receptors on this slide)", "", "Effect of the ANS on the Heart:", "", "Parasympathetic stimulation:", "o Decrease heart rate by decreasing the rate of depolarization, or the rate of rise", "to threshold, of the pacemaker potential;", "o Decrease the conduction of the electrical impulses through the AVN, increasing", "AV nodal delay; this means that it will take longer for the stimulus to pass", "through the AVN into the ventricles", "o Decrease contractility of the atrial myocardium, decreasing the force of", "contraction; remember the ventricular myocardium receives little or no", "parasympathetic innervation, and as a result parasympathetic stimulation has", "no effect on contractility of the ventricle", "", "Sympathetic stimulation:", "o Increase heart rate by increasing the rate of depolarization, or the rate of rise,", "of the pacemaker potential to threshold", "o Increase conduction of the electrical impulses through the AVN, decreasing AV", "nodal delay; this means it takes less time for the stimulus to pass through the", "AVN to the ventricle", "o Increase the contractility of the atrial and ventricular myocardium, increasing", "the force of contraction", "", "Remember: the parasympathetic system will only decrease the force of contraction in", "the atria, as the ventricles receive little or no parasympathetic innervation", "", "Cardiac Output:", "", "Cardiac output (CO) → the amount of blood pumped by each ventricle in one minute;", "CO = HR x SV", "", "Stroke volume (SV) → the amount of blood pumped out of each ventricle during systole;", "typical stroke volumes are 70 - 75 mL", "", "Cardiac output differs from stroke volume in that it is measured per unit time", "", "Factors Affecting Cardiac Output:", "", "As CO = HR x SV by altering the either the heart rate (HR) or the stroke volume (SV), we", "can alter cardiac output (CO)", "", "How do we alter heart rate (HR)?", "o Heart rate may be altered by modifying the activity of the SAN (heart’s", "pacemaker)", "", "How do we alter stroke volume (SV)?", "o Stroke volume can be altered by varying the strength of the contraction of the", "ventricular myocardium", " When the ventricles contract, they do not empty their entire volume of", "blood; altering the strength of contraction of the ventricular", "myocardium will alter the SV, or the volume of blood pumped out", " An increased strength of contraction will increase SV; a decreased", "strength of contraction will decrease SV"] }, { heading: "Lecture 4 recording 18: Factors Affecting Cardiac Output: Heart Rate", id: "lecture-4-recording-18--factors-affecting-cardiac-output--he", items: ["", "Factors Affecting Heart Rate:", "", "The heart has resting autonomic tone; both the sympathetic and parasympathetic", "systems are active at a steady background level (called tone)", "", "One division of the ANS will dominate when its rate of firing raises above a tonic level", "while the other’s falls below", "", "Parasympathetic and sympathetic effects are antagonistic for heart rate", "o To increase HR, sympathetic stimulation will increase while parasympathetic", "stimulation will decrease; to decrease HR, the parasympathetic stimulation will", "increase while sympathetic stimulation will decrease", "", "Under resting conditions, parasympathetic effects dominate for heart rate", "", "To increase HR: must increase the activity of the sympathetic division", "o Increased sympathetic activity and increased release of epinephrine from the", "adrenal medulla will stimulate/increase the activity of the SAN, increasing HR", "and CO", "o As the sympathetic and parasympathetic systems are antagonistic, activity in", "the parasympathetic system must be decreased when sympathetic activity is", "increased", "", "To decrease HR: must increase the activity of the parasympathetic division", "o Increased parasympathetic activity will inhibit or decrease the activity of the", "SAN, thereby decreasing HR and CO", "o As the sympathetic and parasympathetic systems are antagonistic, activity in", "the sympathetic system must be decreased when parasympathetic activity is", "increased", "", "Sympathetic and parasympathetic effects on the heart are extrinsic factors or they", "originate outside the heart", "", "Important: the conducting myocytes in the heart are responsible for initiating the heart", "rate; cells of the SA node are the heart’s pacemaker generating the action potentials", "that are responsible for the HR", "", "Sympathetic and parasympathetic systems can then modify the activity of the SAN", "", "Effect of the ANS on Heart Rate:", "", "Sympathetic stimulation of the SAN → increases the slope of the pacemaker potential", "causing a faster depolarization to threshold; faster rise to threshold increases heart rate", "o Sympathetic stimulation increases the slope of the pacemaker potential by", "increasing the permeability of the F-type and T-type channels", " F-type channels allow Na+ to enter the cell", " T-type channels allow Ca2+ to enter the cell", " Increasing permeability of these channels causes more positive", "charge to enter into the cell, bringing the cells to threshold", "more rapidly", "", "Parasympathetic stimulation of the SAN → decreases the slope of the pacemaker", "potential causing a slower depolarization to threshold; slower rise to threshold", "decreases heart rate", "o Parasympathetic stimulation decreases the slope of the pacemaker potential by:", " Decreasing F-type channel permeability, reducing the movement of Na+", "into the cells", " Increasing K+ channel permeability, causing more K+ to leave the cell,", "making the cell more negative inside", " The pacemaker potential starts from a more negative value,", "closer to the equilibrium potential for K+, taking more time to", "reach threshold", "", "Effect of the ANS on the Pacemaker Potential:", "", "Sympathetic stimulation: pacemaker potential rises more quickly to threshold, or takes", "less time to reach threshold, increasing the heart rate", "", "Parasympathetic stimulation: pacemaker potential rises more slowly to threshold, or", "takes more time, decreasing heart rate", "", "Summary of the Factors Affecting Heart Rate:", "", "Epinephrine, a hormone secreted by the adrenal medulla into the blood, acts similarly to", "norepinephrine released by sympathetic nerves", "", "To increase HR → increased plasma epinephrine, increased release of norepinephrine", "from sympathetic nerves and decreased release of acetylcholine from parasympathetic", "nerves acts on the SAN to increase HR", "", "Sympathetic and parasympathetic systems are antagonistic for heart rate", "", "To decrease HR → (reverse the direction of the arrows); increase parasympathetic", "activity and decrease sympathetic activity to the SAN, as well as reducing epinephrine", "release"] }, { heading: "Lecture 5 recording 19: Factors Affecting Cardiac Output: Stroke Volume", id: "lecture-5-recording-19--factors-affecting-cardiac-output--st", items: ["", "Factors Affecting Cardiac Output:", "", "CO = SV x HR; by altering SV, CO can be altered", "", "Stroke volume (SV) → the volume of blood the ventricle ejects during each contraction,", "or during systole", "o 3 factors that affect the stroke volume: 1) the end diastolic volume (EDV), also", "called the preload, 2) the contractility of the ventricular myocardium, and 3) the", "afterload", "", "Factors Affecting Stroke Volume: EDV:", "o Remember: 3 factors that affect the stroke volume: 1) the end diastolic volume", "(EDV), also called the preload, 2) the contractility of the ventricular myocardium,", "and 3) the afterload", "", "Factor affecting stroke volume: end-diastolic volume (EDV), also called the preload", "o EDV → the volume of blood in the ventricles at the end of ventricular diastole,", "or the volume of blood in the ventricles after the ventricles have completed", "filling", "o The heart has an intrinsic mechanism to alter stroke volume", " Intrinsic means that it that originates or occurs inside, in this case, the", "heart", " This intrinsic mechanism because the ventricles will contract more", "forcefully when they have been stretched prior to contraction", " How are the ventricles stretched? Increased stretch is", "accomplished by filling the ventricles more fully with blood", " The relationship between the end-diastolic volume and stroke volume is", "defined by the Frank-Starling mechanism", " How do we fill the ventricles more fully with blood? Increase the venous", "return, or the amount of blood returning to the heart through the veins;", "this will more fully fill the ventricles with blood, increasing the EDV,", "increasing SV, which ultimately increases CO", "", "Preload → the tension or load on the ventricular myocardium before it begins to", "contract, or the amount of filling of the ventricles at the end of diastole, which is the", "EDV", "", "Sympathetic stimulation of venous smooth muscle will act to increase the return of", "blood to the heart through venoconstriction, increasing filling of the ventricles", "o Sympathetic effect on venous smooth muscle is an extrinsic mechanism, which", "originates outside the heart.", "o Why does the parasympathetic system in the diagram not affect the venous", "volume? Most of the blood vessels in our body receive only sympathetic", "innervation to their smooth muscle and not parasympathetic innervation", "", "The Frank-Starling Mechanism:", "", "Frank-Starling mechanism", "o Intrinsic mechanism", "o Occurs independent of neural or hormonal stimulation", "o The relationship between EDV and SV is defined by the Frank-Starling", "mechanism", "o As you increase EDV, you increase SV", "", "Why does an increased EDV lead to an increased SV?", "o The main determinant for sarcomere length is the degree or amount of", "diastolic filling", "o The initial length of the sarcomere will affect the tension generated during", "contraction", "o As the ventricles become more filled with blood, the cardiac fibers or the", "sarcomeres stretch out, putting more load on the sarcomeres; the ventricles will", "contract more forcefully when they have been stretched, and SV will increase", "o The Frank-Starling mechanism is a length-tension curve", "", "The Frank-Starling mechanism matches the outputs of the two ventricles", "o Ensures the two ventricles pump the same amount/volume of blood and blood", "does not accumulate in one circuit compared to the other", "", "Mechanism of the Length-tension Relationship:", "", "This slide explains why as the ventricle is filled more fully with blood that there is an", "increased force of contraction and a greater stroke volume", "", "(This slide is to help you visually understand the underlined statements)"] }, { heading: "Lecture 5 recording 20: Factors Affecting Cardiac Output: More on Stroke Volume", id: "lecture-5-recording-20--factors-affecting-cardiac-output--mo", items: ["", "Factors Affecting Stroke Volume: Contractility:", "o Remember: 3 factors that affect the stroke volume: 1) the end diastolic volume", "(EDV), also called the preload, 2) the contractility of the ventricular myocardium,", "and 3) the afterload", "", "Remember: the ventricles do not completely empty when they contract", "o Under normal resting conditions, the ejection fraction of the ventricles is", "between 50 - 75%", "o A change in the contractility of the ventricles (contractility = the strength of", "contraction at any given EDV) will alter the volume of blood pumped by the", "ventricles during systole, or the SV", "o Increased sympathetic stimulation will increase the strength of contraction of", "the ventricular myocardium, increasing SV and CO", "o Altering parasympathetic activity will not affect contractility of the ventricles", "and SV, as the ventricular myocardium receives little or no parasympathetic", "innervation", "", "Sympathetic Stimulation Increases Contractility:", "", "The Frank-Starling mechanism still applies under sympathetic stimulation, but during", "sympathetic stimulation, the stroke volume is greater at any given EDV", "o At the same EDV, there is an increase in SV under sympathetic stimulation", "", "Increased contractility will lead to a more complete ejection of the blood, increasing the", "ejection fraction", "o Ejection fraction = SV/EDV", " Under sympathetic stimulation, increased contractility results in a more", "complete ejection of the end-diastolic ventricular volume", "", "Increased sympathetic activity also acts to increase the rate of contraction and", "relaxation", "o Under sympathetic stimulation, the heart contracts and relaxes faster, giving", "more time for the ventricles to fill, despite the increase in heart rate", "", "Mechanisms of Sympathetic Effects on Contractility:", "", "Sympathetic regulation of myocardial contractility acts through a G protein coupled", "mechanism:", "o A number of proteins involved in the excitation-contraction coupling process are", "phosphorylated by intracellular kinases, which enhances contractility", "o These proteins include: L-type Ca2+ channels in the sarcolemma, the ryanodine", "receptor in the sarcoplasmic reticulum membrane, thin filament proteins- in", "particular, troponin, thick filament proteins associated with the cross-bridges,", "and proteins involved in pumping Ca2+ back into the sarcoplasmic reticulum", "(You do not need to know the mechanisms by which this happens)", "", "Factors Affecting Stroke Volume: Afterload:", "", "When the ventricles contract they must generate sufficient pressure to exceed the", "pressure in the arteries and open the semilunar valves to eject their blood into the", "arteries", "o Afterload → the tension against which the ventricle must eject its blood; it is", "closely related to the arterial pressure; often called the ‘load’", " The greater the afterload, the longer the period of isovolumetric", "contraction during which time the heart generates sufficient pressure to", "open the valves and eject blood, and a smaller stroke volume", " As afterload increases, SV decreases", " Afterload is increased by any factor that restricts blood flow through the", "arterial system", " Arterial blood pressure, vascular resistance, stenotic valve"] }, { heading: "Lecture 5 recording 21: The Vascular System", id: "lecture-5-recording-21--the-vascular-system", items: ["", "The Vascular System:", "(Intro slide – do not need to know any information from this slide)", "", "Endothelium:", "", "Our entire circulatory system, including our heart chambers, heart valves, and blood", "vessels, is lined by a smooth, single-celled layer of endothelial cells", "", "The endothelium of the vessels is continuous with the endocardium of the heart", "", "Endothelial cells form a physical lining that blood cells do not normally adhere to in the", "heart and in the blood vessels", "", "Pressures in the Systemic and Pulmonary Circuits:", "", "Blood pressure generated by contraction of the ventricles decreases by the time the", "blood has completed its journey back to the atrium in both the systemic circulation and", "the pulmonary circulations", "", "Pressures in the systemic circulation are much higher than in the pulmonary circulation", "", "Pulmonary vascular resistance is much lower than the systemic total resistance", "o The pulmonary bed has a low resistance because it has relatively large vessels", "throughout and the arterioles have much less smooth muscle than the arterioles", "in the systemic circulation", "", "Arteries:", "", "Walls of arteries contain: smooth muscle, elastic fibers and connective tissue", "", "Muscular walls allow arteries to contract and change diameter", "", "Elasticity permits passive changes in vessel diameter in response to changes in blood", "pressure", "", "Vasoconstriction → contraction of arterial smooth muscle decreases the diameter of", "the artery", "", "Vasodilation → relaxation of arterial smooth muscle increases the diameter of the", "artery", "", "Lined with endothelial cells", "", "Elastic arteries → contain many elastic fibers and few smooth muscle cells; pulmonary", "trunk and aorta; can tolerate pressure changes during the cardiac cycle", "", "Muscular arteries → contain many smooth muscle cells and few elastic fibers; most of", "the vessels in the arterial system are muscular arteries; function to distribute blood", "throughout the body", "", "Arterioles → smallest of the arteries; composed of 1 to 2 layers of smooth muscle cells;", "resistance vessels in the body; play a very important role in determining our mean", "arterial pressure, or our blood pressure"] }, { heading: "Lecture 5 recording 22: Arterioles and Extrinsic Factors Altering Arteriolar Resistance", id: "lecture-5-recording-22--arterioles-and-extrinsic-factors-alt", items: ["", "Arterioles:", "", "Walls of arterioles have an abundance of circular smooth muscle that forms rings", "around the arterioles", "o This allows the state of constriction of the arteriolar smooth muscle to be", "regulated", "", "Functions: regulate blood flow to organs by regulating the amount of blood flow to", "capillary beds supplying that organ and play a role in determining our mean arterial", "pressure (MAP), or our average blood pressure during the cardiac cycle (also called", "blood pressure)", "", "Arterioles have a small enough radius to offer considerable resistance to blood flow and", "are called resistance vessels", "", "Arterioles and Resistance to Blood Flow:", "", "Altering the diameter of a blood vessel will alter resistance to flow:", "o When diameter is decreased this increases resistance to flow and reduces the", "flow to organs; when diameter is increased this decreases resistance to flow and", "increases the flow to organs", "", "Arterioles:", "o Small diameter vessels and their small diameter offers significant resistance to", "flow, which is why there is a large decrease in mean arterial pressure as the", "blood flows through arterioles", "o Arterioles in individual organs can alter their diameter", "o The pattern of blood-flow distribution depends upon the degree of arteriolar", "smooth muscle contraction within each organ and tissue", "o Arterioles play an important role in determining our MAP, or our blood", "pressure, and by altering their diameter, the arterioles can alter blood flow to", "different organs and tissues", "", "Arterioles and Resistance to Blood Flow:", "o Arteriolar smooth muscle has intrinsic or basal tone:", " Tone - partial contraction in the absence of external factors such as", "neural or hormonal stimuli", " Other factors can then increase or decrease the intrinsic/basal tone", " These factors may be extrinsic or intrinsic", " Extrinsic factors: external to the organ or tissue and", "alter whole body needs, such as MAP, and include", "nerves and hormones", " Intrinsic factors: local controls which include", "mechanisms independent of nerves or hormones by", "which organs and tissues alter their own arteriolar", "resistances, thereby self-regulating their blood flow", "", "Extrinsic Controls: Nerves and Hormones:", "o Extrinsic factors: are external to the organ or tissue and include nerves or", "hormones to exert their effects on arteriolar smooth muscle", " Sympathetic innervation to arteriolar smooth muscle but little, or no,", "parasympathetic innervation", " The sympathetic nerve fibers release norepinephrine to cause", "vasoconstriction (do not need to know receptors)", " The sympathetic neurons are seldom completely inactive, but", "discharge at some basal level called sympathetic tone", "(Sympathetic neurons cause some degree of tonic constriction", "in addition to the vessels' intrinsic tone)", " Sympathetic tone can be increased, causing further", "vasoconstriction, or decreased, causing vasodilation", " Sympathetic innervation to the arteriolar smooth muscle is", "important for regulating MAP", " Sympathetic system regulates MAP by influencing", "arteriolar resistance throughout the body", " Noncholinergic, nonadrenergic neurons affect arteriolar smooth muscle", " Release nitric oxide, a vasodilator", " Hormone: epinephrine", " Released from the adrenal medulla into the blood", " Acts on arteriolar smooth muscle to cause vasoconstriction or", "vasodilation, depending on receptor to which it binds (do not", "need to know which receptor causes vasoconstriction or", "vasodilation)"] }, { heading: "Lecture 5 recording 23: Arterioles and Local Controls Altering Arteriolar Resistance", id: "lecture-5-recording-23--arterioles-and-local-controls-alteri", items: ["", "Local Controls: Active Hyperemia:", "", "Local controls: mechanisms independent of nerves or hormones; mechanisms by which", "the organ or tissue alters its own arteriolar resistance, thereby regulating its own blood", "flow", "o Active hyperemia → local control which acts to increase blood flow when the", "metabolic activity of an organ or tissue increases", " Hyperemia → an excess of blood in the vessels supplying an organ or", "tissue", " Arteriolar smooth muscle is sensitive to local chemical changes in the", "extracellular fluid surrounding the arterioles, such as oxygen or carbon", "dioxide levels or pH", " Local chemical changes are the result of changes in metabolic activity", " These altered chemical changes act on smooth muscle in the arterioles", "to cause vasodilation and increase blood flow", " Does not involve any nerves or hormones", "", "Local Controls: Flow Autoregulation:", "o Flow autoregulation:", " Locally mediated changes in arteriolar resistance also occur when a", "tissue or organ experiences a change in its blood supply resulting from a", "change in blood pressure", " An increase in arteriolar pressure will increase blood flow to an organ; a", "decrease in arteriolar pressure will decrease blood flow to an organ", " Altered blood flow will change the concentration of local chemicals", "(oxygen, carbon dioxide and hydrogen ions)", " The change in the level of local chemicals will alter the state of", "constriction of the arteriolar smooth muscle, altering blood flow to", "bring the concentration of local chemical substances back to normal", " Occurs at a constant metabolic activity and is the result of a change in", "pressure in an organ and, as a result, blood flow", " Can occur when the blood pressure to an organ increases or", "decreases", " No nerves or hormones are involved in the mechanism of flow", "autoregulation", "", "Local Controls: Flow Autoregulation:", "", "Flow autoregulation is not only mediated by changes in local chemical factors, but also", "by the myogenic response", "o Myogenic response → the direct response of arteriolar smooth muscle to", "stretch", " An increase in arterial pressure and blood flow causes arterial walls to", "stretch, in addition to changing levels of local chemical factors.", "Arteriolar smooth muscle responds to this stretch by contracting. This", "will reduce blood flow to the organ toward normal levels.", " At the same time there is an increased stretch in the arteriolar walls due", "to the increased blood flow, there is an increase in oxygen levels and a", "decrease in metabolites. These changes in these local chemicals will also", "act to constrict the arteriolar smooth muscle, to bring levels back to", "normal.", "o Flow autoregulation → occurs in response to both changes in local chemical", "factors and the degree of stretching of the arteriolar smooth muscle (myogenic", "response)", "", "More Local Controls:", "", "Reactive Hyperemia:", "o Form of flow autoregulation", "o Occurs at constant metabolic rate", "o Occurs due to changes in the concentrations of local chemicals", "o Occlusion of blood flow → greatly decreases oxygen levels and increases", "metabolites → arterioles dilate → blood flow greatly increases once occlusion", "removed"] }, { heading: "Lecture 6 recording 24: Capillaries", id: "lecture-6-recording-24--capillaries", items: ["", "Capillaries:", "", "Thin walled vessels one endothelial cell thick", "", "Supported by a basement membrane", "", "Contain no smooth muscle or elastic fibers", "", "Function in the rapid exchange of material between the blood and the interstitial fluid", "", "Adjacent endothelial cells are joined laterally by tight junctions but leave gaps of", "unjoined membrane called intercellular clefts", "o Intercellular clefts act as channels or water-filled spaces between endothelial", "cells through which small water-soluble substances can pass through", "", "May have fused-vesicle channels", "o Endothelial cells contain large numbers of endocytic and exocytic vesicles which", "fuse together to form continuous vesicular channels across the cell", "", "Types of Capillaries:", "", "3 types of capillaries: continuous capillary, fenestrated capillary, sinusoidal capillary", "", "Continuous Capillary:", "", "Continuous capillaries:", "o Uninterrupted/complete endothelium and continuous basement membrane", "(basal lamina)", "o Tight junctions between adjacent endothelial cells", " Often incomplete in capillaries, leaving intercellular clefts that allow for", "the exchange of water and other very small molecules between the", "blood plasma and the interstitial fluid", "o Have the lowest permeability of all capillary types allowing the exchange of", "water, small solutes, and lipid-soluble material only", "o Plasma proteins, other large molecules, platelets and blood cells cannot pass", "through continuous capillaries", "o Found in most tissues", "o Pericytes → lie external to the endothelium; may help stabilize the walls of", "blood vessels and help regulate blood flow through capillaries", "", "Continuous Capillaries:", "(Slide showing another view of a continuous capillary)", "", "Fenestrated Capillaries:", "", "Fenestrated capillaries:", "o Endothelial cells have numerous fenestra or pores", " Fenestra → membrane-lined cylindrical conduits that run completely", "through the endothelial cell, from the capillary lumen to the interstitial", "space", "o Surrounded by an intact or complete basement membrane", "o Fenestra or pores allow for the rapid exchange of water and solutes, including", "larger solutes such as small peptides", "o Found in tissues where capillaries are highly permeable, such as endocrine", "organs, the choroid plexus, the GI tract and the kidneys", "o Lipid-insoluble molecules may move through intercellular clefts as well as", "through the fenestrae", "o Fenestrae make this type of capillary much more permeable than continuous", "capillaries", "", "Sinusoids:", "", "Sinusoids (sinusoidal capillaries):", "o Large diameter, flattened and irregularly shaped", "o Called discontinuous capillaries", "o Have very large fenestrae and large gaps between adjacent endothelial cells", "o Basement membrane very thin or absent", "o Allow the free exchange of water and solutes, including large substances such as", "red blood cells, cell debris, and plasma proteins", "o Found only in liver, bone marrow and spleen", "", "Microcirculation:", "", "Capillaries are part of the microcirculation, or the circulation of blood through the", "smallest vessels in the body", "o These vessels includes arterioles, metarterioles, capillaries, venules and veins", "o A capillary bed can be supplied by more than one arteriole", " If one arteriole becomes blocked, blood can enter the capillary bed by", "another arteriole", " Blood flow to capillary beds is variable", " Precapillary sphincters → ring of smooth muscle which guards the", "entrance to the capillary", " Contract and relax in response to local conditions to alter the", "flow of blood in the capillary beds", " Receive no innervation", "o In the microcirculation, capillaries branch from arterioles or metarterioles", " Metarterioles → also called precapillary arterioles; small blood vessels", "arising from an arteriole, pass through a capillary network and empty", "into a venule; contain smooth muscle cells enabling them to regulate", "blood flow by changing diameter; are not ‘true’ capillaries as they have", "smooth muscle cells", "", "Distribution of Blood Flow at Rest and During Exercise:", "", "Our body redirects our blood flow depending on our body’s needs by increasing and", "decreasing blood flow to different capillary beds"] }, { heading: "Lecture 6 recording 25: Capillary Exchange", id: "lecture-6-recording-25--capillary-exchange", items: ["", "Capillary Exchange:", "", "Materials are exchanged across the walls of capillaries by diffusion, vesicle transport or", "bulk flow", "", "Blood flows very slowly through capillaries to maximize the time for the exchange of", "substances between the plasma and the interstitial fluid", "", "Diffusion → net movement of substances from a region of high concentration to a", "region of low concentration", "o Diffusion looks at the movement of one substance only down its own", "concentration gradient", "o Diffusing substances have only a short distance to travel across capillaries, as", "capillaries have a small diameter and have a thin capillary wall due to the fact", "that they are only one endothelial cell thick", "o Mechanism by which nutrients, oxygen and metabolic end products cross", "capillary walls", "o Substances that are lipid-soluble can diffuse across the plasma membrane of", "endothelial cells", "o Substances that are lipid-insoluble must move through a water-filled channel", "(intercellular cleft, fenestrae found in fenestrated capillaries and sinusoids, or", "fused vesicle channels)", "", "Transcytosis → a process involving vesicles in which endothelial cells pick up material on", "one side of the plasma membrane by pinocytosis or receptor-mediated endocytosis,", "transport the vesicles across the cell, and discharge the material on the other side by", "exocytosis", "o Vesicles may fuse together to form a water-filled channel, called a fused vesicle", "channel, from one side of the endothelial cell to the other through which", "substances may move", " Substances move through the fused vesicle channel by diffusion", "", "Capillary Exchange:", "", "Bulk flow → the movement of protein-free plasma across the capillary wall", "o Various constituents of the fluid cross the capillary wall in bulk, or as a unit", "o During bulk flow, the quantity of solutes moving across capillary walls in the", "plasma is extremely small compared to the much larger transfer of solutes that", "occurs by diffusion", " The function of bulk flow is not the exchange of nutrients and metabolic", "end products across capillary walls but rather the distribution of the", "extracellular fluid volume (ie. Bulk flow is important for distribution of", "extracellular fluid volume and less important for exchange of nutrients", "and metabolic end products)", " Extracellular fluid includes the plasma and the interstitial fluid", " Normally, there is more interstitial fluid than plasma", "o Filtration → movement of protein-free plasma by bulk flow from the capillary", "plasma to the interstitial fluid through water-filled channels", "o Reabsorption → movement of protein-free plasma by bulk flow from the", "interstitial fluid to the capillary plasma", "o The concentration of solutes in the filtered fluid, with the exception of plasma", "proteins, is the same as in the plasma", "", "Bulk Flow: Hydrostatic Pressure:", "", "Bulk flow looks at the movement of protein-free plasma across the capillary wall", "", "Bulk flow is driven by different pressures; it occurs because of differences in the", "hydrostatic and colloid osmotic pressures between the capillary plasma and the", "interstitial fluid", "", "Hydrostatic pressure → the force of a fluid against a membrane", "o Capillary hydrostatic pressure → the pressure exerted by the blood on the", "inside of the capillary walls and forces protein-free plasma out of the capillaries", "into the interstitial fluid", "o Interstitial fluid hydrostatic pressure → is the pressure exerted on the outside of", "the capillary wall by the interstitial fluid and forces fluid into the capillaries; this", "pressure is very negligible and does not contribute significantly to bulk flow", "", "Bulk Flow: Colloid Osmotic Pressure:", "", "Colloid osmotic pressure → the osmotic pressure due to the presence of impermeable", "proteins", "o The proteins are impermeable (they cannot cross capillary walls)", " As a result the concentration of proteins will not be equal in the plasma", "and in the interstitial fluid", " The difference in protein concentration between the plasma and the", "interstitial fluid creates an osmotic force; the proteins draw fluid", "towards them, into the compartment that they occupy, as water moves", "from a region of high water concentration to a region of low water", "concentration", " Solutes such as sodium or potassium do not have this effect as they can", "move across capillary walls through pores or water-filled channels", " Solutes such as sodium and potassium have equal", "concentrations in the plasma and in the interstitial fluid", "o Blood colloid osmotic pressure → the osmotic pressure due to the presence of a", "large number of non-permeating plasma proteins, such as albumin, within the", "blood; proteins pull water into the capillaries", "o Interstitial fluid colloid osmotic pressure → is the result of the small amount of", "proteins which do escape the capillaries into the interstitial fluid; favors fluid", "movement out of the capillary, but it is very small and does not contribute", "significantly to bulk flow", "", "Bulk Flow: Net Exchange Pressures:", "", "Net exchange pressure = PC + πIF – PIF – πC (you do not need to memorize this formula,", "but understand how net filtration pressure is calculated)", "o P = hydrostatic pressure; pi = colloid osmotic pressure; C – capillary; IF -", "interstitial fluid", "o The net pressure is the sum of the outward pressures and the inward pressures", " Outward pressures = capillary hydrostatic pressure and the interstitial", "fluid osmotic pressure", " Inward pressures = the osmotic force due to the plasma protein", "concentration and the interstitial fluid hydrostatic pressure", "(Below: for the net pressures at the arterial and venous ends of the capillary you do not", "need to know the numbers (ie 35 vs 15 mmHg hydrostatic pressure, but understand that", "this pressure decreases along the length of the capillary and why this is more filtration at", "arterial end and more absorption at venous end), understand what hydrostatic pressure", "and colloid osmotic pressure are)", "", "Arterial end of the capillary:", "o Capillary hydrostatic pressure (arterial end) ~ 35 mmHg", " Hydrostatic pressure will decrease as blood moves along the length of", "the capillary towards the venous end", " Pushes fluid out of the capillary", "o Blood colloid osmotic pressure (due to proteins in the blood) ~ 28 mmHg", " Draws fluid into the capillary", " Blood colloid osmotic pressure remains the same along the length of the", "capillary", "o Interstitial fluid hydrostatic pressure is ~ 0mmHg", " Does not cause movement of fluid", "o Interstitial fluid colloid osmotic pressure ~ 3mmHg", " Causes fluid to move out of the capillary", "o At the arterial end of the capillary: net pressure is 35 + 3 – 0 – 28 = 10 mmHg", " This is a positive number and favors filtration of fluid from the capillary", "into the interstitial fluid", "", "Venous end of the capillary:", "o Capillary hydrostatic pressure (venule end) ~ 15mmHg", " Pushes fluid out of the capillary", "o Blood colloid osmotic pressure (due to protein in the blood) ~ 28mmHg", " Draws fluid into the capillary (as it did at the arterial end)", "o The interstitial fluid hydrostatic pressure and the interstitial fluid colloid", "osmotic pressure also have the same values at the venous end as at the arterial", "end of the capillary", " Interstitial hydrostatic pressure ~ 0 mmHg", " Does not cause the movement of fluid", " Interstitial fluid colloid osmotic pressure ~ 3 mmHg", " Causes fluid to move out of the capillary", "o At the venous end of the capillary: net pressure is 15 + 3 – 0 – 28 = -10 mmHg", " This is a negative number and favors the absorption of fluid from the", "interstitial fluid into the capillary", "", "The four factors that determine the net filtration pressure are termed the Starling forces", "", "Net Filtration and Net Reabsorption Along the Capillary:", "", "The capillary hydrostatic pressure changes significantly along the length of the capillary", "o 35 mmHg at the arterial end and 15 mmHg at the venous end due to friction", "between the flowing blood and the capillary wall", "", "The transition between filtration and reabsorption occurs where the sum of the", "outward pressures is equal to the sum of the inward pressures", "o As the hydrostatic pressure at the arterial end is greater than at the venous end", "of the capillary, this transition does not occur in the exact middle between the", "arterial and venous ends of the capillary, but occurs closer to the venous end of", "the capillary", " More filtration than absorption occurs along the length of the capillary", "", "The difference excess filtered fluid moves back into the lymphatic system to eventually", "return to the venous system (you do not need to know the numbers (litres of fluid) just", "that more fluid is filtered than absorbed; excess is returned to the lymphatic system)"] }, { heading: "Lecture 6 recording 26: Venous System", id: "lecture-6-recording-26--venous-system", items: ["", "Distribution of Blood Volume:", "", "At rest, ~ 60% of the blood volume is found in the venous system", "o Liver, bone marrow, and skin have a large volume of blood", "", "Veins:", "o Expand and recoil passively with changes in pressure", "o High capacitance vessels as can store large amounts of blood", "o Highly distensible, expanding easily at low pressures and have little elastic recoil", "o Reservoir for blood", "", " Venous Valves:", "", "Venous system is a low pressure system", "", "Venous valves → composed of two leaflets or folds; prevent the backflow of blood into", "the capillaries", "o Aid in returning blood to the heart and ensuring blood flows in one direction", "only", "o Compartmentalize the blood within the veins, so the weight of the blood is", "distributed between the compartments", "", "Varicose veins occur when the walls of the veins near the valves become weakened or", "stretched and the valves do not work properly; blood pools in the veins and vessels", "become distended", "", "Mechanisms for Venous Return:", "", "Smooth muscle in veins", "o Innervated by sympathetic neurons which cause contraction smooth muscle to", "increase pressure", "", "Skeletal muscle pump", "o Compresses veins", "o Venous pressure increases, forcing more blood back to heart", "", "Respiratory pump (will talk about more in respiration)", "o Inspiration causes an increase in venous return", "", "Venous Return and the Frank-Starling Law:", "", "Relationship between venous return and the Frank-Starling law:", "o Skeletal muscle pump, respiratory pump and increased sympathetic activity to", "venous smooth muscle will increase venous return by increasing venous", "pressure", "o Increased venous return to the heart will increase the end-diastolic volume", "o ……now we have the Frank Starling mechanism: increase EDV → increase", "cardiac fiber length → increase force during contraction → increase SV"] }, { heading: "Lecture 7 recording 27: The Lymphatic System", id: "lecture-7-recording-27--the-lymphatic-system", items: ["", "The Lymphatic System:", "", "There is more filtration than absorption along the length of a capillary; the excess fluid is", "returned to the circulatory system by the lymphatic system", "", "Components of the Lymphatic System:", "", "Lymphatic system → consists of a system of small organs, called lymph nodes, and", "tubes, called, lymphatic vessels, through which lymph flows", "", "Lymphatic capillaries:", "o Distinct from blood capillaries", "o Also made of only a single layer of endothelial cells resting on a basement", "membrane", "o Have large water-filled channels that are permeable to all interstitial fluid", "components, including proteins", "o No tubes flow into them (ie they have a round ‘end’)", "o Interstitial fluid enters the lymphatic capillaries through bulk flow", "", "Lymphatic capillaries empty into lymph vessels", "", "Lymph vessels contain one-way valves to ensure that lymph flows in one direction only:", "into the right atrium", "", "Lymph passes through lymph nodes which play a role in defense and are part of the", "immune response", "", "Components of the Lymphatic System:", "", "Lymphatic capillaries:", "o Closed ended (no vessels flow into them)", "o Extend into the interstitial space surrounding tissue cells", "o Thin walls to allow tissue fluid, or interstitial fluid, to enter the lymphatic", "capillaries", " The fluid is called lymph once it enters the lymphatic system", "", "Mechanism of Blood Flow:", "", "The lymph system returns interstitial fluid to the circulatory system, along with small", "amounts of plasma proteins that have escaped the blood vessel capillaries", "", "Mechanisms that contribute to the flow of lymph within the lymphatic system:", "o Lymph vessels beyond the lymphatic capillaries have smooth muscle", " Generates rhythmic contractions, responds to stretch, innervated by the", "sympathetic nervous system", "o One-way valves", "o Skeletal muscle contractions", "o Respiratory pump"] }, { heading: "Lecture 7 recording 28: Blood Pressure", id: "lecture-7-recording-28--blood-pressure", items: ["", "Arterial Blood Pressure:", "", "Blood pressure is determined by the volume of blood in the vessels and the compliance", "of a vessel", "o Compliance → ability of a vessel to distend and increase volume with increasing", "transmural pressure, which is the pressure inside the vessel minus the pressure", "outside the vessel", " Compliance = ΔVolume/ ΔPressure (Δ = change) (do not memorize this", "formula)", " The greater the compliance of a vessel, the more easily it can be", "stretched", "", "During systole, the ventricle pumps blood into the adjacent artery", "o Approximately 1/3rd of the volume of blood ejected by the ventricle leaves the", "artery; the remainder of the stroke volume remains in the arteries during", "systole, distending the arterial walls and increasing the arterial pressure", "o When ventricular contraction ends, the stretched arterial walls recoil passively,", "and blood continues to be driven into the arterioles during diastole, even", "though no new blood is entering the artery from the ventricle", "o This passive recoil maintains perfusion through the capillaries while the", "ventricles are in diastole", "o As blood leaves the arteries, the arterial volume and pressure slowly decrease", "o The next ventricular contraction occurs while the artery walls are still stretched", "by the remaining blood and this means that the arterial pressure does not", "decrease to zero", "", "Large arteries (aorta) act as pressure reservoirs due to their elastic recoil and maintain", "blood flow while the ventricles relax", "", "Arteries are compliant (but not as compliant as veins)", "", "Arterial Blood Pressure:", "", "Systolic pressure → the maximum arterial pressure reached during peak ventricular", "ejection", "", "Diastolic pressure → the minimum arterial pressure reached just before ventricular", "ejection begins", "", "Arterial pressure is generally recorded as systolic pressure divided by diastolic pressure", "", "Pulse pressure → systolic pressure minus the diastolic pressure (PP = SP – DP)", "", "Blood Pressure:", "(You do not need to memorize this table or the symptoms of high or low blood pressure", "talked about in this slide)", "", "120/80 mmHg is normal blood pressure", "", "Hypertension → is defined as chronically increased arterial blood pressure, or high", "blood pressure", "", "Hypotension → abnormally low arterial blood pressure", "", "Mean Arterial Pressure (MAP):", "", "Blood pressure changes during the cardiac cycle", "o Maximal during systole and minimal during diastole, that is it is pulsatile", "", "MAP = diastolic pressure + (pulse pressure/3) (do not memorize this formula)", "", "MAP is the pressure driving blood into the tissues averaged over the cardiac cycle", "(Remember: you need pressure to create flow)", "o At pressures below 60 mmHg the tissue cells in the body will not get sufficient", "blood and the oxygen and nutrients they need", "", "The blood pressure is pulsatile as the blood leaves the heart, that is, it increases and", "decreases during systole and diastole", "o The aorta is very compliant and dampens (or reduces) the pulsatile output of", "the left ventricle, thereby reducing the pulse pressure", "o As the distance from the heart increases, the pulse pressure decreases due to", "the cumulative effects of elastic rebound along the arterial system", " At the level of the aorta we see very large waves, but at the level of the", "arterioles the waves become smaller and smaller until they disappear", " The pressure surge from the ventricles is absorbed as it moves along the", "arterial system and eventually disappears at the level of the arterioles", " No pressure oscillations are seen in the capillaries", "", "Mean Arterial Pressure (MAP):", "", "MAP decreases as the distance from the heart increases", "", "The largest drop in pressure occurs at the level of the arterioles", "o The large pressure drop is due to the high resistance of the arterioles", "o Arterioles are small diameter arteries and provide resistance to blood flow, can", "alter state of constriction of smooth muscle"] }, { heading: "Lecture 7 recording 29: Factors Controlling Mean Arterial Pressure", id: "lecture-7-recording-29--factors-controlling-mean-arterial-pr", items: ["", "Mean Arterial Pressure:", "", "Maintaining sufficient mean arterial pressure is a prerequisite for ensuring adequate", "perfusion or blood flow to all our organs and tissues", "", "MAP is maintained within a specific range", "o Too low a blood pressure would mean that tissues of the body would not", "receive sufficient oxygen and nutrients, and waste products would accumulate", "o Chronically high blood pressure can cause damage to the arteries, the heart and", "kidneys, along with other organs in the body", "", "Mean systemic arterial pressure (MAP) is the arithmetic product of two factors:", "o MAP = CO x TPR", " CO = cardiac output", " TPR = total peripheral resistance", " CO and TPR are the main factors used to calculate the mean arterial", "pressure", "", "TPR is the combined resistance to flow of all the systemic blood vessels", "o Note: Systemic blood vessels and not pulmonary vessels as the pulmonary", "circulation provides little resistance to flow", "o Friction between the blood and the walls of the blood vessels produces", "resistance, which impedes blood flow", " Factors that alter total peripheral resistance alter blood flow", "o Major site of resistance in the systemic circuit → arterioles", " Changes in TPR are due primarily to changes in the resistance of the", "arterioles", " TPR is determined primarily by total arteriolar resistance", " Blood flowing through arterioles experiences resistance as it", "contacts the arteriolar wall, as they have a small diameter, and", "the pressure drop through the arterioles will be great", "", "Summary of Factors Controlling MAP:", "(This slide is a summary of all the concepts we have looked at so far. As you go through this", "slide, think about each of those concepts)"] }, { heading: "Lecture 7 recording 30: Cardiovascular Regulatory Mechanisms", id: "lecture-7-recording-30--cardiovascular-regulatory-mechanisms", items: ["", "Regulation of Mean Arterial Pressure:", "", "Short-term regulation:", "o Seconds to hours", "o Baroreceptors reflexes modify the activity of autonomic nerves supplying the", "heart and blood vessels as well as changes in the secretion of hormones", "o Adjusts cardiac output (CO) and total peripheral (TPR) resistance by ANS", "", "Long-term regulation:", "o Adjust blood volume", "o Restore normal salt and water balance through mechanisms that regulate urine", "output and thirst", "", "Arterial Baroreceptors:", "", "Arterial baroreceptors are mechanoreceptors that detect changes in your blood", "pressure", "o Carotid sinus and the aortic arch baroreceptors", "o Respond to changes in MAP as well as changes in pulse pressure", " Respond to changes in pressure when the walls of the vessel stretch and", "relax", " Pulse pressure is the difference between the systolic and the diastolic", "pressures", "", "Afferent neurons travel from the baroreceptors to the brainstem and provide input to", "the neurons of the cardiovascular control center", "", "Baroreceptor Action Potential Frequency:", "", "The rate of discharge of the carotid sinus baroreceptor is directly proportional to the", "MAP", "", "Baroreceptor Action Potential Frequency:", "", "The baroreceptors continuously generate action potentials in response to ongoing", "pressure in the arteries", "", "An increase in will increase the frequency of action potentials generated by the", "baroreceptors", "", "A decrease in MAP will decrease the frequency of firing of the baroreceptors", "", "An increase in pulse pressure can occur with the calculated MAP still being normal", "o An increase in pulse pressure will cause an increase in the overall action", "potential frequency", "", "The Medullary Cardiovascular Center:", "", "Medullary cardiovascular center:", "o Located in the medulla oblongata in the brainstem", "o The neurons in this center receive input from the baroreceptors which", "determines the frequency of action potentials sent from the medullary", "cardiovascular center to alter vagal stimulation (parasympathetic) to heart and", "sympathetic innervation to heart, arterioles and veins", "o Increase in arterial pressure → increase the rate of firing of the arterial", "baroreceptors → signals medullary cardiovascular center to decrease", "sympathetic activity to the heart, arterioles and veins, and increase", "parasympathetic neuron activity to the heart → decrease the arterial pressure", "", "Baroreceptors adapt to sustained changes in arterial pressure", "o Only used for short term regulation of blood pressure", "", "Other Reflexes:", "o Chemoreceptors primarily function to regulate respiratory activity", " Aortic and carotid bodies (We will look at in respiration; do not need to", "know for cardiovascular section)"] }, ], cell: [ { heading: "Lecture 1 recording 1: Introduction to Cell Physiology", id: "lecture-1-recording-1--introduction-to-cell-physiology", items: ["", "Cell Physiology:", "o Cell → functional unit of a living organism", "", "Basic Components of the Cell:", "o Cells have different structures and different functions", "o All cells contain: a plasma (cell) membrane which surrounds the cell surface, cell", "organelles which compartmentalize the cell and perform specific functions, and the", "interior of the cell which consists of the nucleus and the cytoplasm.", " Cell organelles: membrane-bound or non-membrane bound", " Cytoplasm: the region outside the nucleus and is composed of cytosol, a gel-like", "fluid, in which the cell organelles are suspended", " The nucleus is the largest organelle in the cell", "", "Plasma (Cell) Membrane Functions:", "o Functions of the plasma (cell) membrane:", "1. Physical barrier between the intracellular (ICF) and extracellular (ECF) fluids", " Keeps organelles and proteins inside cell", " Maintains difference in ion composition between ICF and ECF", " Maintains homeostasis – things may change outside the cell but inside", "remain constant", "2. Cell-to-cell communication", " Contains receptors which bind signaling molecules", "3. Structural support", " Contains connections composed of proteins which anchor cells to each", "other or to extracellular materials", "4. Transport", " Plasma membrane is selectively permeable- some substances may", "simply move across the plasma membrane but most require specific", "transport proteins (transporters, carriers, channels etc.) to cross. It is", "therefore selectively permeable, allowing certain molecules to move", "across but not others."] }, { heading: "Lecture 1 recording 2: Composition of Biological Membranes", id: "lecture-1-recording-2--composition-of-biological-membranes", items: ["", "Biological Membranes:", "o The cell/plasma membrane and the intracellular membranes surrounding organelles are", "composed of a double layer of lipid molecules with embedded proteins", " The predominant lipid is the phospholipid and biological membranes are called", "phospholipid bilayers", " Phospholipid bilayer – 2 layers of phospholipids with embedded", "proteins", " Biological membranes have different ratios of lipids and proteins", "", "Lipids:", "o Biological membrane lipids (cell/plasma membrane and membranes surrounding", "organelles) are amphipathic", " Amphipathic molecule – contains polar and nonpolar regions", " Amphipathic lipids found in biological membranes include", "phospholipids, cholesterol, glycolipids", "", "Structure of a Phospholipid:", "o Polar head group: phosphate attached to glycerol, a nitrogen-containing chemical", "group, and glycerol backbone", " Polar head group is hydrophilic (water-loving or dissolves in water)", "o Nonpolar tail: 2 fatty acid chains composed of carbon and hydrogen atoms", " Fatty acid chains may be: saturated (no double bonds) or unsaturated", "(containing 1 or more double bonds)", " Nonpolar tail is hydrophobic (water-fearing or does not dissolve in water)", "", "Structure of a Phospholipid Bilayer:", "o Phospholipids spontaneously form bilayer when put in water.", " Polar heads face aqueous environment, either the ECF or ICF", " Nonpolar tails form hydrophobic core", " Bilayer is the structure of the plasma membrane and the organelle membranes", "Steroids:", "o Cholesterol:", " Steroid lipid", " Amphipathic", " Nonpolar groups: carbon-hydrogen rings and a carbon-hydrogen", "chemical group attached to one of the rings", " Polar group: hydroxyl group", " Found in the cell/plasma membrane", " Function: maintains proper membrane fluidity", " Very important part of plasma membrane: there is almost one molecule", "of cholesterol for each molecule of phospholipid in the cell/plasma", "membrane (organelle membranes contain very little cholesterol)", "Glycolipids:", "o Lipids with CHO (carbohydrate) attached", "o Glycolipids are found in the outer leaflet of the plasma membrane", "o Amphipathic due to presence of sugar", "o Form the glycocalyx", " Glycocalyx: A layer of carbohydrates linked to lipids or membrane proteins", "", "", "", "Membrane Proteins:", "o 2 types: integral (intrinsic) or peripheral (extrinsic)", "o Intrinsic:", "o", "o", "o", " Amphipathic – inserted into phospholipid bilayer of plasma/cell membrane and", "partially span membrane or are transmembrane proteins (completely cross", "phospholipid bilayer of membrane)", " Comprise the majority (70%) of all proteins", " Examples: transporters or channels", "Peripheral:", " NOT amphipathic", " Attached at the outer or inner surface of the membrane (do not penetrate into", "the phospholipid bilayer)", "Carbohydrates may be attached to proteins facing the extracellular surface of the", "plasma membrane and these are called glycoproteins. Form the glycocalyx along with", "glycolipids.", "Proteins are distributed unequally between the two halves of the plasma membrane", "and this is related to the function of the protein.", " Ie. A receptor in the membrane has binding sites facing the ECF so signally", "molecules may arrive at the cell and bind to their receptors. These binding sites", "do not face inside the cell"] }, { heading: "Lecture 1 recording 3: Cell Junctions", id: "lecture-1-recording-3--cell-junctions", items: ["", "", "", "Cell Junctions:", "o Specialized connections that stabilize interactions and promote communication", "between cells", "Desmosomes:", "o Adhering junctions that anchor cells together in tissues subject to considerable", "stretching or mechanical stress", " Ie. Heart muscle", "o Maintain structural integrity of tissue", "o Made of proteins called: plaques, cadherins, intermediate filaments", " Plagues: on cytoplasmic surface of cell; anchor cadherins", " Cadherins: link cells together", " Intermediate filaments: anchor cytoplasmic surface of desmosome to", "components inside cell to provide structural support", "Tight junctions:", "o Found in epithelial tissue specialized for molecular transport", " Epithelial tissue - composed of cells laid together in sheets with the cells tightly", "connected to one another. Epithelial cells have two surfaces that differ in both", "structure and function.", "o Made of proteins called occludins which:", "1. Form nearly impermeable junctions", "2. Link adjacent cells together", "3. Limit the movement of molecules between cells, forcing molecules to pass", "through the cell, or cross the plasma membrane (molecules can only cross the", "plasma membrane if they can diffuse through the lipid bilayer or have specific", "proteins in the membrane)", "", "4. Limit the movement of integral membrane proteins and lipids", "Gap junctions:", "o Transmembrane channels linking the cytoplasms of adjacent cells", "o Made of proteins called connexons", "o Electrically and metabolically couple cells", " Electrically – allow ions to move between cells", " Metabolically – allow small molecules such as nutrients to move between cells", "o Called communicating junctions as ions and molecules can move from one cell through", "the gap junction proteins (connexons) to another cell"] }, { heading: "Lecture 1 recording 4: Cell Organelles", id: "lecture-1-recording-4--cell-organelles", items: ["", "", "", "", "", "Nucleus:", "o Functions: transmission of genetic information to next generation of cells and contains", "the information needed for protein synthesis", "o Contains:", " Chromatin – DNA and associated proteins", " Nuclear envelope – double layered porous membrane surrounding nucleus", "(composed of 2 phospholipid bilayers)", " Nuclear pores – pores in the nuclear envelope that allow molecules to move in", "and out of the nucleus", " Nucleolus – site of synthesis of ribosomal RNA", "Structure of the Nucleus:", "o Nuclear envelope is made of 2 phospholipid bilayers, the inner and outer phospholipid", "bilayer", "o Nuclear envelope has nuclear pores", " Watery channels made from proteins which allow molecules to move in and out", "of the nucleus (DNA too large to pass through the nuclear pores and remains in", "the nucleus)", "Most Cells Have One Nucleus Except….", "o Red blood cells – no nucleus", "o Skeletal muscle – many nuclei in one skeletal muscle cell (multinucleate)", "Ribosomes:", "o Not surrounded by phospholipid bilayer", "o Function: protein synthesis", "o Composed of a small and large subunit:", " Large and small subunit are not functional when separate", " Large and small subunit join to form a functional ribosome, or one capable of", "protein synthesis", " Functional ribosomes may be found free in the cytoplasm or bound to the rough", "endoplasmic reticulum (RER) – proteins made in the cytoplasm have a different", "final destination in the cell than those made at the RER", "Endoplasmic reticulum (ER):", "o Fluid filled membranous system", "o 2 types: rough (RER) and smooth (SER) endoplasmic reticulum", "", "", " RER – flattened sacs with ribosomes attached to outer surface", " SER – branched tubular structure with no ribosomes attached to outer surface", "Functions of the ER:", "o RER – synthesizes proteins and performs post-translational modifications needed to", "produce a functional protein", "o SER – synthesizes lipids, stores calcium (in muscle; called the sarcoplasmic reticulum),", "drug detoxification (in liver)", "Golgi apparatus:", "o Composed of cisternae (flattened sacs)", "o Receives vesicles which contain proteins that were made at the RER", "o Functions: post-translational modifications of proteins made at the RER, sorts and", "packages proteins into vesicles. Proteins in these vesicles may be: secreted from the", "cell, become integral membrane proteins, or become proteins of the lysosomes, ER or", "Golgi itself"] }, { heading: "Lecture 1 recording 5: More Cell Organelles", id: "lecture-1-recording-5--more-cell-organelles", items: ["", "", "", "", "", "Lysosomes:", "o Contain hydrolytic enzymes which break large molecules into small subunits", "o Enzymes are only active at an acidic pH of 5.0 in the lysosome", "o Degrade extracellular and intracellular debris (recycle worn out organelles and destroy", "bacteria or viruses brought into the cell by fusing with them)", "Peroxisomes:", "o Contains oxidative enzymes which use oxygen to remove hydrogen from molecules,", "breaking them down", "o Break down fatty acids, alcohol and drugs", "o Abundant in liver and kidney", "o Hydrogen peroxide is a by-product of the actions of the oxidative enzymes and is toxic", " Peroxisomes have an enzyme called catalase which breaks down hydrogen", "peroxide into water and oxygen", "Mitochondria:", "o Make ATP or energy – important for cellular respiration, or the process of converting", "nutrients into ATP", "o Contain double phospholipid membrane (nucleus and MIT are only two organelles with", "double phospholipid membrane)", " Outer membrane", " Inner membrane is folded into tubules called cristae", "Mitochondria:", "o Cells that need more energy have more MIT", "o Have own DNA – only organelle other than nucleus to have DNA", "Cytoskeleton:", "o Non-membrane bound organelle (only ribosomes and cytoskeleton have no", "phospholipid bilayer surrounding them)", "o Composed of protein filaments or cytoskeletal filaments", "", "", "General functions: maintain cell shape, maintain the position of organelles in", "the cell, and mediated cell and organelle motility", "Cytoskeletal filaments:", "o Cytoskeletal filaments include:", " Microfilaments – made of the protein actin", " Intermediate filaments – many different proteins act as intermediate filaments", "(intermediate filaments are part of desmosomes)", " Microtubules – made of the protein tubulin"] }, { heading: "Lecture 2 recording 6: Vesicular Transport", id: "lecture-2-recording-6--vesicular-transport", items: ["", "", "", "Vesicular transport:", "o Vesicular transport is a form of transport that uses vesicles to move substances across", "biological membranes", " Endocytosis – uptake of material into the cell using vesicles containing material", "that pinch off from the plasma membrane and enter the cytoplasm of the cell", " 3 types of endocytosis – phagocytosis, pinocytosis, receptor-mediated", "endocytosis", " Exocytosis – release of material from the cell using vesicles containing material", "that fuse with the plasma membrane and release their contents into the", "extracellular fluid", "Endocytosis and exocytosis:", "o Endocytosis – materials are brought into the cell using vesicles", "o Exocytosis – materials are released from the cell using vesicles", "Phagocytosis and pinocytosis:", "o Phagocytosis", " Also called cell eating", " Uses extensions of the plasma membrane called pseudopodia to surround", "material being brought up into the cell", " Used for bringing large particles into the cell, such as bacteria or cell debris from", "nearby cells", " Process used by white blood cells", "o Pinocytosis", " Also called cell drinking", " Plasma membrane simply ‘indents’ below the particles to be brought into the", "cell (does not use pseudopodia)", " Plasma membrane pinches together once it has indented and the", "vesicle containing particles brought into the cell is called an endocytic", "vesicle", " Nonspecific process – simply brings in extracellular fluid and substances", "dissolved in that fluid", " Used to ingest small molecules, ions and nutrients (cannot bring in large things", "into the cell such as bacteria or cell debris)", "o Steps of phagocytosis:", "", "", "", " Once activated, the phagocytic cell moves to the material it will ingest", " Steps of phagocytosis include:", " Recognition of substance to be ingested", " Attachment of phagocyte to the substance to be ingested", " Pseudopodia reach around substance and come together to form a", "phagosome inside the phagocytic cell", " Fusion of the phagosome to a lysosome to form phagolysosome", " Destruction of ingested substance by lysosomal enzymes", " Release of end products into the cell or out of the cell by exocytosis", "Receptor-mediated Endocytosis:", "o Specific process as it involves receptors which bind specific ligands to be brought into", "the cell", "o Involves cytoplasmic protein called clathrin", " Binding of ligand to receptor produces conformation change in receptor which", "recruits, or causes, clathrin to move to the membrane", " Many receptor-ligand complexes are localized to one area of membrane lined", "by clathrin, therefore can concentrate the ligand that is taken into the cell", " The membrane lined by clathrin containing the receptor-ligand complexes", "indents and a clathrin coated pit is formed (simply the indented membrane with", "clathrin and receptor-ligand complexes)", " A vesicle pinches off containing the receptor-ligand complexes and is lined by", "clathrin", " Clathrin is released from the vesicle", " Vesicle may: deposit contents into the lumen of an organelle, travel across the", "cell and fuse with plasma membrane to release contents outside cell, fuse with", "organelles called endosomes which then sort contents to the Golgi or lysosomes", "Receptor-mediated Endocytosis:", "o Binding of ligand to receptor recruits clathrin to the membrane", "o Many ligand-receptor complexes are found in one area of the membrane, concentrating", "the ligand being brought into the cell", "o The membrane containing the receptor-ligand complex and lined with clathrin on the", "cytosolic surface indents to form clathrin-coated pit", "o The pit separates from the plasma membrane to form a clathrin-coated vesicle", "Exocytosis:", "o The release contents from a cell using vesicles", "o Functions: to secrete specific substances (ie. hormones), release waste products, add", "components of the membrane, such as lipids and proteins, to the plasma membrane", "when vesicles fuse with the membrane. This balances portions of plasma membrane", "removed by endocytosis"] }, { heading: "Lecture 2 recording 7: Driving Forces for Non-vesicular Transport", id: "lecture-2-recording-7--driving-forces-for-non-vesicular-tran", items: ["", "Driving Forces for Non-vesicular Transport:", "o There are transport process that do not utilize vesicles to move substances across", "membranes", "", "", "", " A difference in energy across a membrane acts as a driving force to move the", "substance", " Substances always move from a region of high energy to a region of low energy", "if allowed to move passively", " Driving forces can be chemical, electrical or electrochemical", "Chemical Driving Force:", "o There is a chemical driving force when there is a different concentration of a substance", "on either side of a membrane", "o Molecules move passively from a high to a low concentration, or ‘down’ the", "concentration gradient", "o As the side of the gradient increases, the rate of transport of the substance increases", "o Chemical driving is due to the concentration gradient of a substance", "Electrical Driving Force:", "o Any substance that is charged will be affected by the electrical driving force", "o The electrical driving force exists due to the membrane potential. Cells in our bodies", "have a membrane potential.", "o Membrane potential is a difference in the electrical potential or voltage across a cell", "membrane", " Also called a ‘separation’ of charge across the membrane", "o Any charged substance experiences attractive or repulsive forces due to the membrane", "potential. The membrane potential will ‘push or pull’ a charged substance in different", "directions, depending on the charge on the substance (ie. positive or negative) and the", "membrane potential.", "o Electrical driving force is due to the membrane potential", "Electrochemical Driving Forces:", "o The electrochemical driving force is the sum of the electrical and chemical driving forces", "acting on an ion", " Remember: neutral substances are not affected by the electrical driving force", "o Direction that the electrochemical driving force acts depends on the net direction of the", "electrical and chemical driving forces"] }, { heading: "Lecture 2 recording 8: Movement of Molecules Across Membranes", id: "lecture-2-recording-8--movement-of-molecules-across-membrane", items: ["", "Simple Diffusion:", "o Simple diffusion is the passive movement of a molecules through a biological", "membrane’s lipid bilayer", " Does not require the input of energy", " How well a substance crosses a phospholipid bilayer depend on the solubility of", "the substance in lipid (is it polar or nonpolar) and its size (the smaller the", "substance, the more easily it can move between the phospholipids in the", "membrane). Remember the membrane is made of phospholipids and has a", "nonpolar core due to the presence of the nonpolar fatty acid tails of the", "phospholipids", " Polar = water soluble, lipid-insoluble", " Nonpolar = water-insoluble, soluble in lipids", "", " Substances that move by simple diffusion move from a region where they are", "found in high concentration to a region where they are found in low", "concentration, or ‘down’ their concentration gradient", " Which substances move across a phospholipid bilayer by simple diffusion (SD)?", " Substances which are small may move across a membrane by SD, but", "have to consider their charge (are they polar or nonpolar or do they", "have a charge (positive or negative, like an ion)?", "1. If a substance is small, nonpolar and uncharged, it can cross by", "SD", "2. If a substance is polar and uncharged, it may cross by SD if small", "enough", " If a substance is large, uncharged and polar, it will not cross by SD (it", "does not have a charge, but being polar and large will not allow it to", "cross by SD)", " Any substance that has a charge (positive or negative), regardless of its", "size (small or large) cannot cross by SD (For example, ions are very small", "but their positive or negative charge will not allow it them interact with", "the nonpolar tails of the phospholipids and cross by SD)", "Factors Influencing the Rate of Simple Diffusion:", "o There are factors which influence the rate of simple diffusion, in addition to the size and", "lipid solubility of the substance", " Magnitude of the driving force – the greater the concentration difference of a", "substance on either side of the membrane, the greater the magnitude of the", "driving force and the greater the rate of SD", " Membrane surface area – how much membrane is available for substances to", "cross? A larger cell has a bigger surface area than a smaller cell, and more", "molecules of a substance can cross the membrane at one", " Membrane permeability", " The permeability of a membrane to a particular substance depends on", "the nature of the transported substance as well as the properties of the", "membrane. It depends on:", "1. The lipid solubility of the diffusing substance", " Nonpolar substances cross the membrane more readily", "2. Size and shape of the diffusing substance", " Small and more regularly shaped substances cross the", "membrane more readily", "3. Temperature", " At higher temperatures substances move around more,", "which will help them diffuse faster across the", "membrane", "4. Diffusing distance", " This refers to how ‘thick’ the diffusing distance is", "", "", "", "If a substance has to cross more layers of cells, it will", "diffuse much slower than if that substance had to cross", "only one layer of cells", "This is an inverse relationship: a smaller diffusing", "distance results in a faster rate of simple diffusion", "Osmosis:", "(Will be looked at in greater detail in the renal physiology section; know only the basics on", "these slides)", "o", "", "Refers to the net movement of water across a selectively permeable membrane driven", "by a difference in solute concentrations on the two sides of a membrane", " Water flows from a region of high water concentration to a region of low water", "concentration. This is the same as saying water flows from a region of low solute", "concentration to a region of high solute concentration.", " How do we change the concentration of water? We do this by adding a solute.", " Pure water is water with no solute added", " When you add solute, you reduce the “concentration” of water", " Water can move across membranes by simple diffusion (water molecules are", "polar but small); the simple diffusion of water across membranes if limited and", "finite", " Certain tissues have a larger permeability to water, such as the kidneys", " This is achieved by the presence of water channels called", "aquaporins, which water easily moves through", "Osmosis:", "o Remember: water flows from the solution with the lower solute concentration into the", "solution with higher solute concentration"] }, { heading: "Lecture 2 recording 9: Membrane Transport Proteins and Facilitated Diffusion", id: "lecture-2-recording-9--membrane-transport-proteins-and-facil", items: ["", "", "Membrane Transport Proteins:", "o The use of a protein to cross the cell is mediated transport", " 2 forms of mediated transport: facilitated diffusion and active transport", " Facilitated diffusion", " Passive transport: energy is not required in this process as", "substances move passively down their concentration gradient", " Types of proteins involved are carriers or channels", " It is a specific transport process", " Carriers are proteins with specific binding sites for the", "substance to be transported across the membrane", " Channels are selective for a specific ion (ie. a sodium", "ion) or a type of ion (ie. may allow cations only or", "anions only to pass through)", "Carrier-mediated Facilitated Diffusion:", "o", "", "Involves transport proteins called carriers which have a specific binding site for the", "substance to be transported", "o These proteins bind the substance and move it across the plasma membrane, from a", "region of high concentration to a region of low concentration", "o Does not require the input of energy, such as ATP", "o Example: GLUT family of proteins which are carriers that move glucose across the", "membrane from a region of high concentration to a region of low concentration", "(glucose is nonpolar and uncharged but it is too large to move across the membrane by", "simple diffusion)", "Channel-mediated Facilitated Diffusion:", "o Channels may be selective for a specific ion or type of ion that moves through them", "o Channels do not just allow ions to pass through. For example, aquaporins are water", "channels that are specific for water molecules", "o The direction and magnitude of ion flux through a channel depends on the", "electrochemical gradient of that ion", "o Channels exist in an open or closed state and may be gated. Gating refers to the opening", "(activation) or closing (by deactivation or inactivation) of ion channels. Gating is the", "process of an ion channel transforming between any of its conducting and nonconducting states.", " Channels may be: voltage-gated (changes in voltage cause the channel to open", "or close), ligand-gating (the binding of a substance or ligand to a binding site on", "the channel causes it to open or close) or mechanically-gated (mechanical", "stimuli such as swelling or stretching of a cell causes the channel to open or", "close)"] }, { heading: "Lecture 2 recording 10: Membrane Transport Proteins and Active Transport", id: "lecture-2-recording-10--membrane-transport-proteins-and-acti", items: ["", "Membrane Transport Proteins:", "o The use of a protein to cross the cell is mediated transport", " 2 forms of mediated transport: facilitated diffusion and active transport", " Active transport", " Involves transport proteins with specific binding sites for the", "substance to be transported", " Capable of uphill transport, or moving a substance against an", "electrochemical or concentration gradient from low to high", " Often called pumps", " Utilize energy to mediate uphill transport", " Primary or secondary active transporters obtain energy", "from different sources", " Primary active transport", " Energy source to drive the transport process: ATP", " Example: Na+/K+ pump", " Remember: At rest, a cell has a high [Na+]o and", "high [K+]i. (o= outside the cell; i=inside the cell)", "", "Na+/K+ pump moves 3 Na+ ions out of the cell", "and 2 K+ ions into the cell for every molecule of", "ATP hydrolyzed. This pump moves Na+ and K+", "ions against their concentration gradients.", " Functions of pump: contributes to establishing", "and maintaining the membrane potential of the", "cell and maintains the Na+ and K+ concentration", "gradients", " Secondary active transport", " Energy source to drive the transport process:", "movement of an ion down its electrochemical gradient", " Couples movement of an ion down its electrochemical", "gradient with that of an another substance moving", "against its concentration gradient", " Example: Na+/glucose cotransporter or Na+/H+", "exchanger. In both cases Na+ moving down its", "electrochemical gradient provides the energy to move", "H+ or glucose against its electrochemical (H+) or", "concentration gradient (glucose)", "o", "Transport Rates:", " Simple diffusion: unsaturable transport process as it does not involve proteins", "and binding sites; as you increase the concentration of the substance, you", "increase the movement of substance across the membrane", " Mediated transport: saturable transport process as it involves proteins and", "binding sites; each cell has a limited number of proteins and each protein has a", "limited number of binding sites for a substance. As the concentration of", "substance increases, an increased number of binding sites are occupied. The", "transport rate will plateau, or stop increasing, once all sites are occupied; at this", "point further increasing the concentration will not further increase the transport", "rate."] }, { heading: "Lecture 3 recording 11: Signal Transduction", id: "lecture-3-recording-11--signal-transduction", items: ["", "", "Chemical Messengers:", "o A form of intercellular communication; intercellular – “between cells”", "o May be lipid-soluble or lipid-insoluble", "o Used for the process of signal transduction, which is the sequence of events between", "the binding of a messenger to a receptor and the production of a cellular response", "Properties of Receptors:", "o Receptors have specific binding sites for a specific messenger", "o Receptors show saturation, in that they have a defined number of binding sites for a", "messenger (a single receptor may have only 1 or 2 binding sites for a messenger)", "o Receptors bind different messengers with different affinities. Affinity refers to how", "strong a receptor and messenger bind; high affinity means they bind very strongly a low", "concentrations while low affinity means that the interaction between messenger and", "", "receptor is weaker and it requires higher concentrations of a messenger to bind. Some", "receptors bind a particular substance with high affinity while other receptors bind to", "their substance with low affinity.", "o Receptors may be found on the plasma membrane or intracellularly, in the cytosol or in", "the nucleus", "Intracellular receptors:", "o These receptors are found inside the cell, in the cytoplasm or in the nucleus", "o Lipid-soluble chemical messengers diffuse across the plasma membrane and bind to", "intracellular receptors", "o Example of chemical messengers that bind to intracellular receptors: steroid hormones", "(hormones derived from cholesterol)", "o Chemical messengers which bind to intracellular receptors act as transcription factors", " Transcription factors alter the rate of transcription of mRNA in the nucleus by", "binding to a response element", " A response element is a specific sequence of DNA near the beginning of a gene.", "By binding to the response element, a chemical messenger can alter the rate of", "transcription of a gene, which will alter the rate of translation of the mRNA into", "a protein (each gene contains the instructions for producing a specific protein)", " Transcription factors alter the rate of protein synthesis"] }, { heading: "Lecture 3 recording 12: Membrane-bound Receptors", id: "lecture-3-recording-12--membrane-bound-receptors", items: ["", "", "Membrane-bound Receptors:", "o Chemical messengers that are water-soluble (hydrophilic; lipid-insoluble) cannot diffuse", "across the hydrophobic core of the plasma membrane; bind to receptors on the", "extracellular surface of the plasma membrane", " Examples include peptide or protein hormones", " 3 types of membrane-bound receptors are channel-, enzyme-, or G-proteinlinked receptors", "o Important definitions:", " First messenger – extracellular chemical messenger that binds to a specific", "membrane-bound receptor", " Second messenger – a substance that enters or is generated in the cytoplasm of", "a cell following the binding of the first messenger to its receptor", " Protein kinase – an enzyme that phosphorylates another protein, or adds", "phosphate groups to the protein. By adding phosphate groups to a protein, a", "protein kinase alters the activity of another protein", "Receptors That Are Ligand-gated Ion Channels:", "o A membrane-bound receptor", " This receptor (a protein) has a receptor component with binding sites for a", "chemical messenger and an ion channel component. It is one protein that", "functions both as a receptor and an ion channel.", " Steps of signal transduction:", "1. A first messenger binds to binding sites on the receptor", "2. An ion channel in the receptor protein opens", "", "3. Ions move through the channel. As the ions have a charge, they alter", "the electrical properties of the cell and produce a response.", " This is a fast process as the receptor and ion channel are a single protein", " The channel in the receptor may be a calcium channel. Calcium has many roles", "in the cell.", "Receptors That Function As Enzymes:", "o A membrane-bound receptor", " This receptor (a protein) has a receptor component with binding sites for a", "chemical messenger and intrinsic enzyme activity (intrinsic = within the receptor", "protein)", " Also called receptor tyrosine kinases: the enzyme part of the", "receptor is a kinase that phosphorylates tyrosine amino acid", "residues (ie. adds phosphates to tyrosine amino acid residues)", " The tyrosine kinase part of receptor autophosphorylates or", "phosphorylates tyrosine amino acid residues on the", "receptor (auto = self)", " The phosphorylated tyrosines (phosphotyrosines) on the", "receptor act as docking sites for proteins in the cytoplasm of", "the cell", " Once a protein binds to the phosphotyrosines it is activated", "by phosphorylation, and will bind to other proteins in the", "cell to eventually produce a response"] }, { heading: "Lecture 3 recording 13: More Membrane-bound Receptors", id: "lecture-3-recording-13--more-membrane-bound-receptors", items: ["", "", "", "Membrane-bound Receptors:", "o G-protein linked receptor: membrane-bound receptor that binds extracellular chemical", "messengers", "G-protein Linked Receptors:", "o G-proteins", " Found at the cytosolic surface of the plasma membrane", " Bind guanosine nucleotides (GDP or GTP), and this is why they are called Gproteins (G= guanosine)", " A protein made of 3 subunits called alpha, beta and gamma", " Function as a link between the receptor in the plasma membrane and an", "effector protein, which is an ion channel or an enzyme", " Both the receptor and the effector protein interact with the Gprotein", " Only the alpha subunit of the G-protein binds to GTP or GDP, not the beta and", "gamma subunit", "G-protein Linked Receptors: An Animation:", "(This slide contains an animation which will be looked at in detail in later slides)", "", "G-protein Linked Receptors:", "o Alpha subunit of the G-protein: binds the guanosine nucleotides GDP and GTP", "o", "o", "o", "o", "o", " Alpha subunit: when inactive binds GDP", " Alpha subunit: which active binds GTP", "Binding of an extracellular first messenger to a membrane-bound receptor causes a", "conformational change in that receptor, altering the affinity of the alpha subunit of the", "G-protein for GDP", " The affinity of the alpha subunit for GDP decreases and the affinity for GTP", "increases; the alpha subunit releases GDP and binds GTP", "The G protein will now dissociate from the receptor and the GTP-bound alpha subunit is", "activated and separates from the beta and gamma subunits", "The activated alpha subunit moves to its target protein in the membrane, called the", "effector protein.", " Effector protein is either an enzyme or an ion channel", " The GTP-bound alpha subunit will alter the activity of this effector protein to", "produce a response in the cell", "The activated alpha subunit hydrolyzes, or breaks down, the GTP to GDP and inorganic", "phosphate, returning itself to the inactive state in which it is bound to GDP. The alpha", "subunit recombines with the beta and gamma units, which anchor the alpha in the", "membrane.", "The G-protein with the 3 subunits (alpha, beta and gamma) then recombines with the", "receptor"] }, { heading: "Lecture 3 recording 14: G-proteins and Second Messenger Systems", id: "lecture-3-recording-14--g-proteins-and-second-messenger-syst", items: ["", "", "", "Actions of G-proteins on Ion Channels:", "o How does binding of a first messenger alter the activity of an effector ion channel?", "1. Binding of first messenger to receptor causes conformational change in receptor", "2. Affinity of α-subunit for GTP increases; GDP dissociates, GTP binds", "3. GTP-bound α-subunit dissociates from β and γ; moves to ion channel", "4. Ion channel opens or closes (depending on state of channel prior to binding of", "GTP-bound α-subunit), alters flow of ions across membrane", "Actions of G-proteins on Enzymes:", "o How does binding of a first messenger alter the activity of an effector enzyme?", "1. Binding of first messenger to receptor causes conformational change in receptor", "2. Affinity of α-subunit for GTP increases; GDP dissociates, GTP bind", "3. GTP-bound α-subunit dissociates from β and γ; moves to enzyme", "4. There are different types of G-proteins:", " If the G-protein is a Gs protein, it stimulates or activates the enzyme (S=", "stimulatory); if the G-protein is a Gi protein, it inhibits the enzyme (I=", "inhibitory)", "5. Altering the activity of the enzyme alters the production of a second messenger", "by the enzyme in the cytosol", "cAMP Second Messenger System:", "o cAMP second messenger system – most common second messenger system found in", "the cells in our body", " cAMP = a second messenger", "o", "", "Steps involved in the production of cAMP:", "1. Binding of a first messenger to a receptor causes a conformational change in the", "receptor. This increases the affinity of the alpha subunit for GTP; GTP binds after", "the release of GDP.", "2. The activated alpha subunit of the Gs protein separates from the beta and", "gamma subunits and moves to and binds to adenylyl cyclase, activating it.", " Adenylyl cyclase is a membrane-bound enzyme", " A stimulatory G protein or GS stimulates or activates adenylyl cyclase", "3. The catalytic site of adenylyl cyclase is located on the cytoplasmic surface of", "the plasma membrane; adenylyl cyclase catalyzes the conversion of cytosolic", "ATP molecules into cyclic AMP.", "4. Cyclic AMP acts as a second messenger and diffuses through the cytoplasm", "5. cAMP binds to and activates protein kinase A (PKA), which is also called cyclicAMP-dependent protein kinase.", " PKA requires cAMP to activate it", "6. Activated PKA catalyzes the phosphorylation of proteins in the cell by", "transferring a phosphate group from ATP to cellular proteins", "7. Once these cellular proteins have been phosphorylated, their activity is", "altered, resulting in a cellular response", "cAMP Second Messenger System: An Animation:", "(This slide contains an animation which looks at the cAMP second messenger system)", "", "Calcium as a Second Messenger:", "o Calcium may act as a second messenger in cells", "o Calcium normally found in low concentrations in the cytoplasm", "o Calcium may enter the cell from the extracellular fluid following the binding of a first", "messenger to a receptor", " The receptor may be a receptor that is a ligand-gated ion channel, in which case", "the intrinsic ion channel opens and allows calcium to move into the cell. The", "receptor may be a G-protein linked receptor, which will open a calcium channel", "in the membrane. With either receptor, calcium enters the cell and its", "concentration increases in the cytoplasm.", "o The increase in calcium levels in the cytoplasm is not enough to produce a response in", "the cell; calcium that has entered the cytoplasm from the ECF will bind to receptors on", "an organelle called endoplasmic reticulum (the ER may store calcium; it has a high", "concentration of calcium). Binding of calcium to receptors on the ER causes calcium to", "be released from the ER, further increasing levels in the cell; this is called calciuminduced calcium release as calcium entering the cell from the ECF causes its own release", "from the ER into the cytoplasm.", "o Calcium now acts as a second messenger", "o Calcium activates calmodulin, a cytosolic protein that is normally found inactive in the", "cell; calmodulin requires calcium to activate it", "o Active calmodulin activates a calmodulin-dependent protein kinase", "o The protein kinase phosphorylates proteins in the cell, producing a response"] }, ], blood: [ { heading: "Lecture 1 recording 1: Basic Facts", id: "lecture-1-recording-1--basic-facts", items: ["•", "Facts About Blood:", "▪ Blood → liquid connective tissue composed of different cells (red blood cells, white", "blood cells, platelets) dissolved in plasma. Blood also contains gases, waste products,", "nutrients, and hormones", "▪ Blood is found in the circulatory system, in the blood vessels", "▪ Blood is heavier or more viscous than water", "•", "Functions of Blood:", "1. Transport of substances in blood", "2. Regulation of ion and pH balance", "3. Defense and immune protection", "4. Hemostasis or the prevention of blood loss", "•", "Separation of Blood Cells and Plasma:", "▪ Whole blood may be separated by centrifugation", "o Upper layer in test tube is plasma (makes 55% of blood volume)", "o Middle layer is called buffy coat; contains white blood cells and platelets (<1% of", "blood volume)", "o Bottom layer in test tube is red blood cells (~45% of blood volume)", "o Hematocrit: % of total blood volume occupied by packed red blood cells", "➢ x/y x 100%, where x= the volume of packed red blood cells and y= total", "blood volume", "a. 42% females", "➢ 47% males", "Clinical Significance of Hematocrit Measurement", "▪ Can indicate conditions of low numbers of red blood cells (anemia) or high numbers of", "red blood cells (polycythemia)", "•"] }, { heading: "Lecture 1 recording 2: Plasma", id: "lecture-1-recording-2--plasma", items: ["•", "•", "•", "The Fluid Compartments of the Body:", "▪ 2 major fluid compartments of the body:", "o Intracellular – fluid inside cells", "o Extracellular – fluid outside cells (includes plasma and interstitial fluid)", "Composition of Plasma:", "▪ Plasma – liquid portion of blood containing water, electrolytes, organic molecules, trace", "elements, gases", "o Substances transported by blood include gases oxygen and carbon", "dioxide, nutrients, waste products and hormones", "Functions of Plasma Proteins:", "▪ 4 classes of plasma proteins:", "o Albumins, globulins, fibrinogen, transferrin", "o Major site of synthesis: liver", "o Functions:", "➢ Albumins: contribute to colloid osmotic pressure of plasma,", "carry/transport substances in plasma", "➢ Globulins: clotting factors, enzymes, antibodies, carriers for various", "substances in plasma", "➢ Fibrinogen: forms fibrinogen threads for blood clotting", "➢ Transferrin: transport of iron"] }, { heading: "Lecture 1 recording 3: Blood Cell Types and Hematopoiesis", id: "lecture-1-recording-3--blood-cell-types-and-hematopoiesis", items: ["•", "•", "•", "Blood Cell Types and Numbers:", "▪ 3 types of blood cells:", "o Red blood cells (erythrocytes), white blood cells (leukocytes), platelets", "(thrombocytes)", "o Numbers of blood cells are measured in microliters of blood", "Blood Cell Types and Functions:", "▪ Red blood cells", "o Function: transport of oxygen and carbon dioxide", "▪ White blood cells", "o Polymorphonuclear granulocyte white blood cells are classified according to", "staining characteristics of cytoplasmic granules and structure of the nuclear", "lobes", "➢ Neutrophils, eosinophils, basophils", "o Functions:", "➢ Neutrophils: phagocytes", "➢ Eosinophils: defense against parasites", "➢ Basophils: inflammation", "➢ Monocytes: phagocytes and immune defense; leave the blood stream", "and are transformed into tissue macrophages", "➢ Lymphocytes:", "❖ B-cell: antibody production and humoral immunity", "i. (Definition for clarity only) Humoral immunity:", "immunity mediated by macromolecules found in", "extracellular fluids, such as antibodies, complement", "proteins, antimicrobial peptides. Humoral immunity", "involves substances found in the humors, or body fluids", "❖ T-cell: cellular immunity", "ii. (Definition for clarity only) Cellular immunity: immune", "process that involves the activation of phagocytes,", "antigen-specific cytotoxic T-lymphocytes, and release of", "various cytokines in response to an antigen.", "Hematopoiesis:", "▪ Hemotopoiesis – process of formation of blood cells", "▪ Before birth – yolk sac, liver, spleen", "•", "•", "▪ After birth – bone marrow", "Hematopoiesis:", "▪ All blood cells originate from a pluripotent hematopoietic stem cell, an undifferentiated", "cell capable of giving rise to any type of blood cell", "Factors Regulating Hematopoiesis", "▪ Cytokines", "➢Small secreted proteins", "➢Regulated hematopoiesis", "➢Hormone-like as are released into blood and act on receptors on target cells", "➢Also called hematopoietins, or growth factors that influence development of", "blood cells", "❖ Erythropoietin – regulates production of RBCs", "❖ Thrombopoietin – regulates production of platelets"] }, { heading: "Lecture 1 recording 4: Red Blood Cells", id: "lecture-1-recording-4--red-blood-cells", items: ["•", "•", "•", "•", "Red Blood Cells (RBCs):", "▪ Important characteristics:", "o Biconcave", "o Function: transport of oxygen (and carbon dioxide)", "o Lose nucleus and other organelles during development", "o Contain many hemoglobin molecules", "o Lifespan: 120 days", "Structure of Hemoglobin:", "▪ Hemoglobin (Hb)", "o Composed of heme (non-protein) portion and globin (protein) portion", "▪ Hemoglobin A", "o HbA or adult hemoglobin", "o Single hemoglobin molecule has 4 globin chains (2 alpha and 2 beta chains), 4", "heme groups and 4 divalent iron atoms (divalent; 2+)", "➢ Each iron can bind a single oxygen; each hemoglobin can therefore bind", "4 oxygen", "Hemoglobin and O2 Transport:", "▪ Majority of oxygen in the body is transported in red blood cells bound to hemoglobin", "▪ Hemoglobin binds oxygen in a loose and reversible manner", "o Relaxed binding structure of hemoglobin allows oxygen to bind in a cooperative", "manner, meaning the binding of successive oxygen molecules facilitates or helps", "the binding of the next oxygen", "➢ Oxyhaemoglobin is hemoglobin to which oxygen is bound; it has a", "relaxed binding structure", "o Deoxyhemoglobin has a tight binding structure and has given up oxygen", "o Oxygenation → the process by which a ferrous iron combines with one", "molecule of oxygen", "What Makes CO Inhalation Fatal:", "▪ Hb can bind oxygen, carbon dioxide, nitric oxide and carbon monoxide", "▪", "Hb has a higher affinity for carbon monoxide (200 x higher) than for oxygen, meaning it", "prefers to bind carbon monoxide and does so very tightly, which makes it difficult to", "remove from the Hb", "o Carbon monoxide is colorless, odorless and has high affinity for Hb, making it", "fatal as Hb cannot bind oxygen and deliver it to the body"] }, { heading: "Lecture 2 recording 5: Factors Affecting RBC Production", id: "lecture-2-recording-5--factors-affecting-rbc-production", items: ["•", "•", "•", "•", "•", "Factors Essential for RBC Production:", "▪ 3 different factors:", "o Cytokines: erythropoietin (EPO) stimulates RBC production", "o Dietary factors: iron needed in Hb, folic acid, and vitamin B12", "o Intrinsic factor: made by cells in the stomach and needed for absorption of", "vitamin B12", "Regulation of RBC Production by Erythropoietin:", "▪ Erythropoietin (EPO): cytokine, stimulates RBC synthesis", "▪ Stimulus for EPO secretion from the kidneys: decreased oxygen delivery to the kidneys", "▪ EPO acts on bone marrow hematopoietic stems cells to increase product of RBC", "▪ Decrease in tissue oxygenation → stimulates release of EPO from kidneys → stimulates", "hematopoietic stem cells in bone marrow → increases production of RBC by bone", "marrow → increases oxygen-carrying capacity of blood → increase tissue oxygenation", "▪ Hypoxia: low oxygen concentration in the blood", "o Factors contributing to hypoxia: low blood volume, anemia, low hemoglobin,", "poor blood flow, pulmonary disease (Basically, any factor that reduces the", "ability of blood to carry oxygen (low blood volume, anemia, low hemoglobin),", "that affects delivery of oxygen to tissues (low blood volume and flow) and", "affects ability to take in oxygen (pulmonary disease))", "Uptake and Recirculation of Iron:", "▪ Iron: needed for production of RBC", "▪ Obtained from food and absorbed into blood in intestine", "▪ Transported in blood bound to transferrin (iron transport protein)", "▪ Used in bone marrow to make RBC", "▪ Body iron reserve: 50% iron is from Hb from dying RBC, 25% stored in other ironcontaining proteins, 25% stored in liver bound to ferritin (a protein)", "Recycling of Iron From Old/Damaged RBCs:", "▪ Old or damaged RBC taken up by macrophages in spleen by phagocytosis", "▪ Hemoglobin → broken down into heme and globin", "▪ Heme → broken down into iron and biliverdin", "o Iron → absorbed into blood for erythropoiesis or stored in spleen or liver bound", "to ferritin", "o Biliverdin → converted to bilirubin → secreted into bile and enters small", "intestine", "▪ Globin → broken down into amino acids", "Absorption of Vitamin B12:", "▪ Vitamin B12 required for normal production of RBC", "o Obtained from diet", "o Absorption from GI tract requires intrinsic factor (a protein), secreted by cells in", "stomach wall", "➢ Vitamin B12 and IF form a complex to allow vitamin B12 to be absorbed", "o Pernicious anemia → due to lack of vitamin B12"] }, { heading: "Lecture 2 recording 6: Anemia", id: "lecture-2-recording-6--anemia", items: ["•", "•", "•", "Anemia:", "▪ Anemia: decreased oxygen-carrying capacity of the blood due to a deficiency of RBCs", "and/or hemoglobin contained in the RBCs", "Specific factors leading to anemia:", "▪ Lack of iron", "▪ Pernicious anemia: lack of intrinsic factor or Vitamin B12", "▪ Aplastic anemia: damage of bone marrow due to radiation/drugs", "▪ Chronic kidney disease (reduced level of erythropoietin, EPO)", "▪ Hemolytic anemia: increased breakdown due to abnormal shape of RBC or due to", "immune reactions during transfusion", "▪ Hemorrhagic anemia: increased blood loss due to injury, bleeding ulcers or chronic", "menstruation", "▪ Abnormal structure of hemoglobin", "Specific factors leading to anemia:", "▪ Normal adult hemoglobin: HbA (2 alpha and 2 beta chains)", "▪ Sickle cell disease", "o Have abnormal Hb called HbS", "o Characteristics of disease: sickle-shaped RBC with hard, nonflexible cell", "membranes", "o RBC in sickle cell disease are damaged as they pass through capillaries and this", "leads to hemolytic anemia", "o An autosomal recessive disease (the gene for Hb S has to be inherited from both", "parents)"] }, { heading: "Lecture 2 recording 7: Anemia", id: "lecture-2-recording-7--anemia", items: ["•", "Immunity:", "▪ Refers to process that help a cell or the interior of our body defend against anything", "foreign- it protects our ‘self’ from our ‘non-self)", "▪ 2 types of immunity: innate (natural) immunity and acquired (adaptive/specific)", "immunity", "o Innate/natural immunity", "➢ Immunity we are born with", "➢ Includes non-specific defenses in the body such as physico-chemical", "barriers, or physiological and chemical barriers of the body (skin,", "enzymes in body fluids, acid secretion in stomach, WBCs)", "o Acquired/adaptive/specific immunity", "➢ Acquired over time and upon exposure to foreign pathogens/cells", "•", "•", "➢ Foreign object triggers the immunity to develop", "➢ WBC important", "The White Blood Cell Story:", "▪ WBC", "o Produced from pluripotent stem cells in bone marrow", "o Pluripotent cells converted to: granulocytes (neutrophils/eosinophils/basophils),", "monocytes or lymphocytes (B cells and T cells)", "o T- Lymphocytes", "➢ Production begins in bone marrow", "➢ Migrate to thymus to complete development then return to blood", "o Lymphocytes", "➢ May migrate to peripheral tissues and are returned to circulation by", "lymphatic system", "Role of WBC’s: Two Main Types of Immunity", "▪ Know the differences between innate/natural immunity and acquired/adaptive", "immunity", "Type of Immunity", "Key Features", "INNATE or", "NATURAL", "ACQUIRED or", "ADAPTIVE", "Non-specific", "No memory", "Fast (sec/min/h)", "Specific", "Has memory", "Slow (days/weeks)", "Major cells involved Phagocytes", "(neutrophils and", "macrophages)", "Complement system", "Major molecules", "involved", "•", "Lymphocytes", "(B and T cells)", "Antibodies", "Cytotoxic molecules", "Role of the Immune Systems:", "▪ Appropriate responses of the immune system: defense, remove old/damaged/abnormal", "cells", "▪ Inappropriate responses of the immune system: allergies, autoimmune reactions"] }, { heading: "Lecture 3 recording 8: Inflammation", id: "lecture-3-recording-8--inflammation", items: ["•", "•", "Inflammation:", "▪ The non-specific innate immune response to tissue injury initiates inflammation; part of", "body’s immune response", "Purpose of Inflammation?", "▪ To cause healing and resolve injury, destruction of non-self agents and formation of scar", "tissue (fibrosis).", "•", "Physical Characteristics of Inflammation:", "▪ Redness", "▪ Swelling", "▪ Heat", "▪ Pain", "▪ Loss of function", "(Note: you do not need to memorize the Latin terms)", "•", "•", "Changes in Vasculature (Blood Vessel Wall)", "▪ Changes in vasculature following injury:", "o Release of inflammatory mediators (histamine)", "➢ Histamine causes vasodilation of blood vessels, which increases blood", "flow causing the redness and heat of inflammation", "➢ Histamine causes blood vessels to become leaky or more permeable,", "allowing proteins and fluid to move to the extracellular space. The fluid", "causes the swelling of inflammation.", "Features of Acute (Short-term) Inflammation:", "▪ 2 major components of acute short term inflammation: vascular events and cellular", "events", "o Vascular events – refers to events involving blood vessels", "➢ Release of histamine", "➢ Local blood vessels dilate", "➢ Local blood vessels become leaky", "➢ Accumulation of protein and fluid in the extracellular space", "➢ Inflammatory mediators are released: bradykinin, prostaglandins,", "complement proteins", "o Cellular events – refers to events associated with cells", "➢ Resident macrophages entrap and kill pathogens, release chemical", "signals", "➢ Increased movement of WBCs (neutrophils and monocytes) into", "infected area", "➢ Phagocytosis and destruction of foreign agent"] }, { heading: "Lecture 3 recording 9: Cellular Events Associated with Inflammation", id: "lecture-3-recording-9--cellular-events-associated-with-infla", items: ["•", "•", "Purpose of Inflammation?:", "▪ The destruction of non-self agents", "Cellular Events Associated with Inflammation:", "▪ Cellular events of inflammation act to bring WBCs to the inflamed tissue and kill the", "“non-self” agent", "▪ Cellular events include:", "1. Margination of WBCs – move to edge of blood vessels", "2. Tethering and rolling of WBCs inside blood vessel – attaching of WBC to", "endothelial cells of the blood vessels and slow rolling along the vessel", "•", "•", "3. Activation of WBCs and endothelial cells – involves expression of proteins on the", "surface of neutrophils and endothelial cells", "4. Arrest/firm attachment of WBCs to endothelial cells – neutrophils bind to", "complementary proteins on endothelial cells and stop rolling", "5. Emigration/diapedesis - white blood cells squeeze in between adjacent", "endothelial cells to exit out of the blood vessel and move into the tissue spaces", "6. Chemotaxis of WBCs – WBCs move toward the site of inflammation by", "chemotaxis, a process of cell movement that occurs in response to specific", "molecules or chemical attractants", "7. Recognition of “non-self” by WBCs - at the site of infection, WBCs recognize", "foreign agents by recognizing chemical molecules on their surface", "8. Phagocytosis of “non-self” pathogen by WBCs – process by which foreign", "pathogens or bacteria are engulfed by neutrophils", "Stages of Macrophage Movement from the Blood to the Tissues:", "▪ (Slide shows the stages as listed in previous slide)", "Migration of Neutrophils to the Site of Infection: Chemotaxis and Chemo-attractants", "▪ Chemotaxis - the ability of WBCs to move against a concentration gradient (low → high", "concentration) in response to chemical factors; they move towards the source of a", "chemotactic substance.", "▪ Chemotactic factors (chemo-attractants) - Chemical factors that attract WBCs to the site", "of inflammation", "▪ There are many factors that help in the movement of WBCs to the source of infection", "(DO NOT memorize the list of chemotactic factors on this slide)."] }, { heading: "Lecture 3 recording 10: Destruction of Non-self Agent at the Site of Inflammation", id: "lecture-3-recording-10--destruction-of-non-self-agent-at-the", items: ["•", "•", "Role of Phagocytes at the Site of Infection:", "▪ Phagocyte → a cell that can eat other non-self pathogens or dying cells by engulfing", "them with temporary cytoplasm filled extension of the plasma membrane", "(pseudopodia).", "▪ Examples of phagocytic cells: monocytes, macrophages, dendritic cells and neutrophils", "▪ Steps involved in phagocytosis: (as in Cell Physiology section)", "1. Recognition of substance to be ingested - macrophages have cell-surface", "receptors that recognize certain molecules on the surface of various pathogens", "2. Attachment of phagocyte to the substance to be ingested - this activates the", "process of phagocytosis", "3. Pseudopodia reach around substance and come together to form a phagosome", "inside the phagocytic cell", "4. Fusion of the phagosome to a lysosome to form phagolysosome", "5. Destruction of ingested substance by lysosomal enzymes", "6. Release of end products into the cell or out of the cell by exocytosis", "How do Phagocytes Recognize Bacteria?:", "▪ Phagocytic cells, like macrophages, have receptors called pattern recognition receptors,", "or toll-like receptors", "o", "•", "•", "•", "Receptors recognize a specific pattern of molecules expressed on bacteria, and", "therefore do not have to recognize a specific bacteria", "Role of Opsonization:", "▪ Opsonins :", "o Molecules added to the surface of a bacteria to help in speeding up the rate of", "phagocytosis by macrophages or other phagocytic cells", "o Produced by self or host body", "o Opsonins may be antibodies or complement-type proteins", "▪ Opsonization:", "o Coating of the bacteria with opsonins (either antibodies or complement-type", "proteins) produced by the host body which then facilitates the attachment and", "phagocytosis of the bacteria by the phagocytic cell.", "Steps of Phagocytosis:", "▪ (This slide shows the steps of phagocytosis again)", "Killing by Neutrophils:", "▪ Neutrophils", "o Important in immune response", "o Kill bacteria by 1) oxygen-dependent process or 2) oxygen-independent process", "o Oxygen- dependent killing - corrosive oxygen free radical products are", "synthesized to destroy a foreign body", "o Oxygen-independent killing – use different bactericidal enzymes", "➢ Lysozymes → enzymes which work inside phagolysozomes to degrade", "entire bacteria by proteolytic breakdown", "➢ Lactoferrin → binds to iron and reduces iron in the environment so that", "bacteria cannot grow", "➢ Defensins → drill holes on the surface of a bacteria"] }, { heading: "Lecture 4 recording 11: Role of Complements as Mediators of Inflammation", id: "lecture-4-recording-11--role-of-complements-as-mediators-of", items: ["•", "•", "Complement Proteins: Plasma-derived Mediators:", "▪ Complement proteins", "o Found inactive in plasma", "o Activated by a cascade or step-wise activation process which amplifies the signal", "o Involved in the innate immune response", "o 3 pathways that activate complement proteins (Do not need to know details of", "activation on the chart ie the names of the 3 pathways and the process", "involved)", "Function of Activated Complement Proteins:", "▪ OIL", "o O = opsonization; activated complement proteins act as opsonins, which lead to", "potentiated phagocytosis", "o I = inflammation mediator; activated complement proteins act as", "chemoattractants, attracting other immune cells to the site of inflammation,", "increasing vascular permeability and histamine release from mast cells", "o L = lysis; complement proteins cause lysis of bacteria", "•", "Killing by MAC Formation (Lysis)", "▪ Activated complement proteins may kill a pathogen by forming a membrane attack", "complex or MAC", "o The activated complement proteins come together and form a pore on the", "surface of the bacteria", "➢ Involves complement proteins, therefore part of innate immune", "response"] }, { heading: "Lecture 4 recording 12: Role of B Cells in the Development of Acquired Immunity", id: "lecture-4-recording-12--role-of-b-cells-in-the-development-o", items: ["•", "•", "•", "•", "Role of WBCs in Adaptive Immunity :", "▪ Complement proteins", "o Found inactive in plasma", "o Activated by a cascade or step-wise activation process which amplifies the signal", "o Involved in the innate immune response", "o 3 pathways that activate complement proteins (Do not need to know details of", "activation on the chart ie the names of the 3 pathways and the process", "involved)", "Primary and Secondary Lymphoid Tissue:", "▪ B and T lymphocyte/cell development starts in the bone marrow", "▪ B lymphocytes", "o Remain in bone marrow for development", "▪ T lymphocytes", "o Leave bone marrow during development", "o Move to thymus gland to complete development", "▪ Both B and T lymphocytes move to the blood circulation once developed", "▪ The bone marrow and the thymus are primary lymphoid tissues", "o These are sites where B and T lymphocytes are developed but they are not", "exposed to foreign pathogens or antigens", "▪ B and T lymphocytes move to peripheral lymphoid tissues or nodes", "o Peripheral lymphoid tissues or nodes - where lymphocytes come in contact", "with foreign antigens and fully mature", "➢ Peripheral lymph nodes or tissues are called secondary lymphoid tissues", "o Activated lymphocytes can move back to the blood circulation through the", "lymphatic circulation", "Characteristics of Acquired Immunity:", "▪ Roles of B and T lymphocytes in acquired immunity (3 R’s):", "o Recognize a specific foreign antigen or agent", "o Respond to the antigen by mounting an immune response to bring about their", "destruction", "o Remember the first encounter with the antigen", "➢ Important feature of acquired immunity", "General Structure of Antibody: Recognition Molecule on B Cells:", "▪ Antigens → molecules that are specifically recognized by an antibody to form an", "antigen-antibody complex.", "•", "•", "o Immunogen → an antigen that can activate an immune response", "▪ Antibody → belongs to the globulin class of plasma proteins (Immunoglobulin class)", "o Y shaped molecule with two heavy chains and two light chains. The light and", "heavy chains are connected to each other by disulfide bridges.", "o The site formed by the combination of light and heavy chains on both arms of", "the Y-shaped molecule forms the highly specific binding site of the antibody (ie.", "This is where antigen binds)", "Acquired Immunity: Role of B Cells:", "▪ Humoral component of acquired immunity", "o Humoral immunity: the aspect of immunity mediated by macromolecules such", "as secreted free-circulating antibodies found in the humors, or body fluids", "o Humoral immunity: developed when naïve B cells in the lymph nodes are", "exposed to foreign antigens", "o B cell binds a complementary antigen and then undergoes mitosis, or clonal", "expansion", "➢ In clonal expansion, all progeny carry the same antigen specificity", "➢ During antigen-specific clonal expansion, two groups of B cells are", "formed", "❖ One group differentiates into short-lived plasma cells", "▪ Plasma cells → synthesize antibodies specific to the", "foreign antigen that initiated the clonal expansion. The", "free antibody molecules contribute to humoral", "immunity and are known as free circulating antibodies.", "❖ Other group retains the specific receptor for the foreign antigen", "and circulates in the plasma as memory cells", "▪ Memory cells → long-lived cells which retain the", "memory of the first exposure for many years to come", "❖ The antibody-like molecules on the surface of the B cells act as a", "receptor to recognize a specific antigen", "Humoral Immunity (Major Defense Against Bacteria):", "▪ Free circulating antibody molecules bind specific foreign antigens to form antigenantibody or immune complexes", "o Functions:", "➢ Antibodies can neutralize toxic molecules produced by bacteria. This is a", "“direct” effect of antibodies.", "➢ An indirect effect involves use of the antibody as an *opsonin or for the", "purpose of *complement activation.", "❖ Once complement proteins are activated, the effects of OIL", "could set in", "❖ OIL stands for opsonizaton, inflammation mediator and lysis"] }, { heading: "Lecture 4 recording 13: Role of T Cells in the Development of Acquired Immunity", id: "lecture-4-recording-13--role-of-t-cells-in-the-development-o", items: ["•", "Key Features of T Cell-mediated Acquired Immunity:", "▪ Acquired immunity has a cell-mediated component", "o", "•", "•", "•", "Cellular immunity is an immune response that does not involve antibodies, but", "rather activation of phagocytes, T-cells and the release of various cytokines", "o Cellular immunity:", "➢ Virus infections, cancer cells and transplanted organs", "➢ Involves T cells: cytotoxic T cells, helper T cells and memory T cells", "o T cells perform the three Rs,", "➢ Recognize a specific foreign antigen", "➢ Respond to a foreign antigen by generating a cellular immune response", "➢ Remember the first encounter with a foreign antigen", "o Unique feature of the T cell mediated immune response: T cells require the", "foreign antigen to be presented in an unique manner known as “antigen", "presentation”", "Processing and Presentation of External Foreign Antigen:", "▪ T cells require the foreign antigen to be presented in a unique manner, known as", "“antigen presentation”", "▪ Antigen presentation:", "o A process whereby a host cell, such as a macrophage or a dendritic cell, engulfs", "the foreign protein, or antigen and presents it to the T cell complexed with the", "host’s proteins", "➢ Antigen presentation:", "❖ Antigen is taken up by a macrophage and processed into smaller", "pieces by the macrophage’s enzymes. The small pieces of the", "foreign protein are then loaded on to a specific intracellular", "protein called MHC (major histocompatibility complex protein).", "The small pieces of the antigen are then presented on the", "surface of the antigen presenting cell to a naïve T cell.", "MHC “Facts”:", "▪ MHC proteins are coded for by MHC genes.", "▪ Two types of MHC proteins: MHC I and MHC II type", "o MHC I is found in virtually all nucleated cells", "o MHCII is found specifically in antigen-presenting cells such as macrophages and", "dendritic cells", "Summary: Acquired Immune Response:", "▪ How does a bacterial infection lead to antibody synthesis in secondary lymphoid tissue?", "o Steps for the development of acquired immunity:", "o Following a cut or break in the skin, bacteria invade the host body and are", "transferred through blood or a lymphatic vessels into a lymph node", "o In the lymph node:", "1. The bacterium can be recognized specifically by B cells which then", "undergo clonal expansion to form plasma cells and memory B cells. The", "plasma cells can produce free circulating antibodies. These antibodies", "are specific to the foreign antigen.", "(B cells → clonal expansion → antibodies specific to the foreign antigen)", "•", "•", "2. In the lymph node, a macrophage or dendritic cell can engulf the same", "bacterium, and present the foreign antigen to a Helper T cell. The helper", "T cells can proliferate to become activated helper T cells. These", "activated T cells can produce cytokines which can interact with the B", "cells that undergo clonal expansion.", "(Macrophage → antigen presentation → activated T cells make", "cytokines which interact with the B cells)", "▪ T cells and B cells do not act alone", "o During B cell-mediated development of immunity, T cells interact to provide", "help via production of cytokines", "Immunological Memory:", "▪ Antigen is injected and the host body produces antibody", "▪ Immunological memory is an important features of acquired immunity", "o The first or primary immune response → slow to develop and the amount of", "antibody generated is not large", "o The host body remembers the first encounter to the antigen and if exposed to", "the same antigen again, the host responds in a fast and quick manner which is", "known as the secondary response", "o Secondary immune response → antigen A is injected a second time and the", "magnitude of the response is large and very quick", "▪ This feature of memory is effectively used for vaccination purposes to provide immunity", "against diseases", "Practical Immunization:", "▪ Two types of immunity that can be achieved: active immunity and passive immunity", "▪ Active immunity:", "o Direct exposure to the antigen or exposure by vaccination", "o The antibodies are self-generated.", "o The immunity is not immediate- days to weeks", "o Duration of the immunity: months to years", "o Combat future infection", "▪ Passive immunity:", "o Occurs when pre-formed antibodies are transferred from a mother to the fetus", "during pregnancy or by nursing in the postnatal stage", "o Does not take time to acquire (immediate)", "o Duration of the immunity: short-lived", "o Provides help for the child until their own immune system is fully developed"] }, { heading: "Lecture 5 recording 14: Platelets and Hemostasis", id: "lecture-5-recording-14--platelets-and-hemostasis", items: ["•", "•", "Hemostasis:", "▪ The prevention of blood loss", "▪ Platelets are important in hemostasis", "o Found in the middle “buffy coat” mixed with the white blood cells", "Why is Hemostasis Necessary?:", "▪ Pro-hemostatic factors prevent blood loss", "▪", "▪", "•", "•", "•", "Anti-hemostatic factors are factors which keep the blood fluid", "Our body tries to maintain a state where blood can circulate smoothly, without", "formation of unnecessary clots", "Key Steps of Hemostasis:", "• Step 1: vasoconstriction (vascular spasm)", "▪ A ruptured blood vessel contracts to minimize blood loss at the site of the cut", "o Factors which trigger vasoconstriction:", "➢ An injury stimulates pain receptors that activate nerve endings that are", "directly affected by the cuts, causing vasoconstriction", "➢ Injury to blood vessel smooth muscle, causing vasoconstriction", "➢ Local injury to the platelets causes the release of serotonin, which acts", "as a vasoconstrictor", "• Step 2: primary hemostasis or platelet plug formation", "▪ Platelets aggregate to form a platelet plug or a white thrombus (It is known as white", "thrombus because platelets are colorless cells)", "• Step 3: secondary hemostasis or blood clotting/coagulation (red thrombus)", "▪ If the bleeding does not stop after the formation of the white thrombus, blood clotting", "enzymes are activated to form a stronger gel-like clot at the cut site. This is known as", "red thrombus as it is reddish in color.", "• The word thrombus refers to a blood clot", "Where Do Platelets Come From?:", "▪ Platelets = thrombocytes", "▪ Platelets originate from the pluripotent stem cells of the bone marrow", "o Pluripotent stem cells are converted to cells called megakaryocytes", "o Platelets are pinched off from the cytoplasmic part of megakaryocytes", "Megakaryocytes and Platelets:", "(This slide shows platelets pinching off from the cytoplasm of megakaryocytes)"] }, { heading: "Lecture 5 recording 15: Platelet Structure and Function", id: "lecture-5-recording-15--platelet-structure-and-function", items: ["•", "•", "Structure of Platelets:", "▪ Platelets contain organelles and the following are important to note:", "o Vesicles called alpha granules and dense granules", "o DO NOT CONTAIN a nucleus", "▪ Contain glycogen for energy", "▪ Contain contractile proteins actin and myosin", "▪ Contain surface glycoproteins which act as receptors", "▪ Contain canaliculi", "Contents of Platelet Granules:", "▪ Alpha granules contain large molecules:", "o Adhesive protein von Willebrand factor, growth factors, some blood clotting", "factors and cytokines", "▪ Dense granules contain small molecules:", "o ADP and ATP, 5-hydroxytryptamine (serotonin) and calcium", "•", "•", "•", "Platelet Plug Formation (Primary Hemostasis):", "▪ Step 1: Adhesion:", "o Platelets must adhere to a surface in the process of hemostasis", "➢ Normally do not stick to the smooth surface of blood vessels but an", "injury to blood vessels disrupts the endothelial layer and exposes the", "underlying collagen", "➢ Platelets adhere to the collagen tissue using von Willebrand factor", "❖ von Willebrand factor is a protein secreted by platelets and", "endothelial cells", "❖ Once secreted, von Willebrand factor can change conformation", "and bind to platelets", "❖ von Willebrand factor forms a bridge between the damaged", "vessel wall and the platelets", "▪ Step 2: Activation of platelets:", "o Binding of platelets to collagen triggers the release of chemicals from their", "storage granules (ADP and serotonin)", "o ADP and serotonin act locally on the platelets to change metabolism, shape, and", "expression of receptors on the surface of the platelet", "▪ Step 3: Aggregation of platelets:", "o New platelets to adhere to old ones by a positive feedback effect which rapidly", "forms a platelet plug inside the vessel", "The Platelet Plug:", "▪ von Willebrand factor is secreted by platelets and endothelial cells and binds to exposed", "collagen molecules in the damaged blood vessel wall, changes its own conformation and", "becomes bound to platelets", "▪ von Willebrand factor forms a bridge between the damaged vessel wall and the", "platelets", "▪ The activated platelets express a fibrinogen receptor on their surface, which can bind to", "fibrinogen, a plasma protein, and other platelets to form a network, or lattice-like", "structure, which ultimately forms the plug", "▪ During this process the activated platelets also secrete thromboxane A2 and ADP, which", "attract more platelets to the cut site, and the aggregation continues", "▪ After the plug is formed, the plug can contract using its contractile proteins actin and", "myosin to tighten the plug and seal the cut site", "Roles of Activated Platelets:", "▪ Adhesion of platelets triggers activation of the platelets", "▪ Once platelets are activated, they secrete the compounds:", "o Serotonin (5HT) and ADP:", "➢ Serotonin acts as a vasoconstrictor", "➢ ADP plays a role in further platelet aggregation", "o Thromboxane A2:", "➢ Promotes further platelet aggregation and vasoconstriction of the", "vascular smooth muscle which will reduce blood flow to the cut site", "o", "Upon platelet activation, phospholipids exposed on the surface of the platelet", "aid in the conversion of prothrombin to thrombin, which acts to promote", "further platelet aggregation"] }, { heading: "Lecture 5 recording 16: Factors Affecting Platelet Plug Formation", id: "lecture-5-recording-16--factors-affecting-platelet-plug-form", items: ["•", "•", "•", "Why Does Platelet Plug Not Continuously Expand?:", "▪ Why does the plug not expand along the undamaged endothelium of the blood vessel?", "o Adjacent undamaged endothelial cells synthesize and release prostacyclin, and", "nitric oxide which inhibit the spread of the platelet plug along undamaged", "endothelium", "➢ Prostacyclin (prostaglandin I2 or PGI2) inhibits platelet aggregation", "➢ Nitric oxide (NO) inhibits platelet adhesion, activation and aggregation", "Effects of Arachidonic Acid Metabolites:", "▪ The innate response of inflammation occurs within seconds of the initiation of injury.", "Following some time lag, chemicals are released from the blood vessel wall which start", "the process of healing by initiating the formation of the platelet plug at the site of the", "cut.", "▪ Membrane damage, or a disturbance in the cell membrane, initiates the production of", "arachidonic acid from membrane phospholipids.", "▪ In the lipoxygenase pathway:", "o Arachidonic acid is converted to leukotrienes by the enzyme lipoxygenase, and", "these chemicals then initiate inflammatory responses of swelling", "▪ In the cyclooxygenase pathway:", "o Arachidonic acid is converted to a prostaglandin by an enzyme known as", "cyclooxygenase or COX", "o Platelets and endothelial cells both have the cyclooxygenase enzyme, but they", "have different isoforms, or variants, of the enzyme. As a result, the hemostatic", "responses will vary. The prostaglandins play a role in hemostatic effects that", "help to prevent blood loss.", "▪ Generally, the acute inflammatory response precedes hemostatic effects", "Effect of Aspirin on Hemostasis:", "▪ Aspirin is prescribed to prevent clot formation in patients that have a potential risk for", "heart attacks", "▪ Cyclooxygenase pathway:", "o Arachidonic acid is produced from membrane phospholipids as a result of", "membrane rupture and injury", "o There are two isoforms of the cyclooxygenase enzyme, called COX 1 and COX 2", "o Healthy endothelial cells:", "➢ Subject to the action of the COX 2 enzyme", "➢ COX 2 activity results in the synthesis of prostacyclin and this has an", "anti-hemostatic effect. The prostacyclin synthesized from arachidonic", "acid keeps the plug from expanding to adjacent undamaged endothelial", "cells.", "o", "▪", "▪", "In platelets:", "➢ Subject to the action of the COX 1 enzyme", "➢ COX 1 produces thromboxane A2 and has a pro-hemostatic effect, or", "favors the formation of a platelet plug", "Aspirin can inhibit the actions of both COX-1 and COX-2", "o Once COX-1 is inhibited in the platelets, the chances of producing thromboxane", "A2 are completely blocked. Platelets are non-nucleated cells and once their", "enzyme is inhibited, the actions of the COX 1 enzyme are completely blocked, as", "they cannot synthesize new COX 1 enzyme.", "o Once COX-2 is inhibited, healthy endothelial cells will eventually start", "synthesizing new COX-2 enzymes as they are nucleated. COX-2 enzymes then", "convert arachidonic acid to prostacyclin.", "o Aspirin can block the COX 1 pathway only and block all the pro-hemostatic", "pathways; COX 2 pathways can overcome the inhibition of aspirin to make", "prostacyclin and keep the vessels vasodilated and decrease platelet aggregation", "Low dose aspirin is used in patients who may have an increased risk of heart attacks to", "prevent clot formation"] }, { heading: "Lecture 6 recording 17: Secondary Hemostasis: Formation of a Blood Clot", id: "lecture-6-recording-17--secondary-hemostasis--formation-of-a", items: ["•", "•", "Secondary Hemostasis:", "▪ Blood clotting is a process by which blood is transformed into a solid gel called a clot, or", "thrombus, and consists of a protein called fibrin. The essential part of a clot is the", "formation of fibrin.", "▪ Secondary hemostasis:", "o Occurs following a platelet plug formation", "o Involves a cascade of enzyme (clotting factors) activation", "o Activation of enzymes occur by proteolytic cleavage", "o Formation of gel-like fibrin clot, in which red bloods cells become trapped and is", "called a red thrombus", "Factors Involved in Blood Clotting:", "▪ 13 factors involved in blood clotting", "o All are present as inactive plasma proteins in the blood", "o Factors are always expressed as Roman numerals", "▪ Factor 4 is ionized calcium (is not a protein)", "▪ Many of the activation reactions take place on the surface of platelets", "▪ Factors are synthesized in the liver", "▪ The first 4 factors in the list, fibrinogen, prothrombin, tissue thromboplastin, also known", "as tissue factor, and calcium, are the most important factors involved in the key steps of", "clotting", "(Make sure you memorize the names of the first 4 factors for studying purposes ie.", "Factor 1 = fibrinogen; factor 2 = prothrombin; factor 3 = tissue thromboplastin;", "factor 4 = calcium. You do not need to know the “names” of the other factors ie.", "Factor IX = Christmas factor)", "•", "•", "Blood Clotting: Key Step:", "▪ Generation of the active thrombin enzyme is the key step in the clot formation pathway", "o An inactive enzyme prothrombin is converted to thrombin by the", "prothrombinase complex", "o Thrombin is the active enzyme which converts the inactive protein fibrinogen to", "the active form fibrin", "➢ Fibrin is an insoluble protein which upon stabilization becomes strong", "strands and forms a mesh-work, or the fibrin clot, in which cells get", "trapped", "Activation of Thrombin:", "▪ There are two pathways by which clotting factors are activated to form a common", "activated factor, which is called factor Xa", "o Factor Xa is directly involved in the formation of active thrombin.", "o In the intrinsic pathway all the factors come from within the blood and the", "blood vessel itself", "o The extrinsic pathway is initiated by some factors outside the blood vessel", "▪ Both pathways, the intrinsic and extrinsic, meet and activate the common factor in the", "common pathway leading to the formation of a blood clot"] }, { heading: "Lecture 6 recording 18: Pathways Leading to the Formation of the Blood Clot", id: "lecture-6-recording-18--pathways-leading-to-the-formation-of", items: ["•", "Traditional/Classical Mechanism of Blood Clotting:", "▪ Blood clotting (=coagulation) prevents excessive bleeding when blood vessels are", "injured.", "▪ 3 interconnected pathways: intrinsic, extrinsic, and common pathways", "▪ Intrinsic pathway → triggered by internal trauma or damage that occurs within the", "blood vessels themselves", "o From endothelial cell injury, exposure to subendothelial collagen, or contact", "with foreign or artificial surfaces", "➢ Endothelial cell injury → damage to the thin layer of cells (endothelial", "cells) lining the inside of blood vessels; can occur due to high blood", "pressure, inflammation, or vascular disease", "➢ Exposure of subendothelial collagen → endothelial layer is disrupted,", "revealing the collagen underneath", "❖ Subendothelial collagen is a structural protein located beneath", "the endothelial cells that line the inside of blood vessels;", "normally hidden from the bloodstream by the intact endothelial", "layer; once the endothelium is compromised, collagen becomes", "exposed to circulating blood and initiates clotting.", "➢ Contact with foreign or artificial surfaces → triggers intrinsic pathway;", "ie medical devices like catheters, heart valves, or synthetic implants that", "come into contact with blood", "o Factor XII encounters negatively charged surfaces and is activated, initiating", "the intrinsic pathway", "•", "•", "➢ Activation in vivo occurs when blood is exposed to collagen fibers", "underlying the endothelium in the blood vessels; collagen has a", "negatively charged surface", "➢ Activation in vitro occurs when blood is exposed to foreign surfaces (ie", "glass test tube, synthetic plastics); uncoated or plain glass in a test tube", "has a naturally negatively charged surface", "Traditional/Classical Mechanism of Blood Clotting:", "▪ Extrinsic pathway → requires exposure to tissue factor (TF or factor III) which is located", "outside the bloodstream or external to the blood", "o Tissue factor → a transmembrane protein found on cells outside the vascular", "endothelium (FYI: on smooth muscle cells, fibroblasts, and pericytes); normally", "not exposed to circulating blood", "o External trauma or physical injury that damages tissues outside the blood", "vessel, (FYI: such as cuts, abrasions, puncture wounds, surgical incisions, or", "blunt force injuries) damages tissues outside the blood vessel to activate", "extrinsic pathway", "➢ Trauma also causes rupture of the vessel wall, allowing blood to leak", "into the surrounding tissues; Factor VII, which normally circulates in the", "blood in its inactive form, comes into contact with TF on the damaged", "extravascular cells and binds to it, activating factor VII", "➢ TF–VIIa complex then activates Factor X", "➢ TF is exposed by proximity to the blood; the trauma simply removes", "the barrier (the intact blood vessel wall) that normally keeps TF and", "blood separate", "Traditional/Classical Mechanism of Blood Clotting:", "• Intrinsic pathway → begins with activation of factor XII, which becomes activated when it", "comes into contact with negatively charged surfaces, such as collagen in vivo or the surface", "of a glass test tube in vitro, to form XIIa.", "▪ Factor XII is the “contact activation factor”", "o In vitro, or outside the body, when blood is collected in an uncoated plain glass", "test tube blood will clot", "➢ The negatively charged uncoated surface of a glass test tube resembles", "a damaged blood vessel wall, which activates factor XII, and triggers", "clotting; coating the glass test tube with siliconenneutralizes the", "negative charge and blood does not clot in vitro; when coated by", "silicone, the glass surface does not trigger the activation of factor XII", "and does not initiate the intrinsic pathway", "• Extrinsic pathway → triggered by external trauma", "▪ External trauma → physical injury that damages tissues outside the blood vessel, such as", "cuts, abrasions, or blunt force injuries that rupture tissues or crush or damage cells; the", "key to this pathway is tissue factor (factor III) which is a protein normally not in contact", "with the blood", "o While the extrinsic pathway is often described as being triggered by external", "trauma, that trauma must still rupture the blood vessel wall to allow tissue", "•", "factor (TF)—which is located outside the blood vessel—to come into contact", "with Factor VII in the blood; when tissue factor and factor VII come into contact,", "factor VII is now activated", "▪ Factor VII is activated when it comes in contact with tissue factors outside a blood", "vessel, in the presence of phospholipids exposed on activated platelets and calcium", "o Factor VIIa then activates factor X", "▪ The extrinsic pathway is activated by tissue damage, and not by blood vessel wall", "damage alone", "• Factor Xa → key enzyme that starts the common pathway", "▪ Factor Xa binds with Factor Va, calcium ions (Ca²⁺), and phospholipids on the surface of", "activated platelets; this complex is called the prothrombinase complex", "o Prothrombinase complex catalyzes the transformation of prothrombin into", "thrombin", "➢ Thrombin converts fibrinogen into long fibrin strands", "➢ Factor XIIIa cross-links the fibrin strands, forming a stable fibrin clot", "• The clotting cascade allows for the strong amplification of the initial signal in response to", "tissue damage and bleeding", "▪ The number of steps also decreases the possibility of accidental activation of the", "clotting process", "Physiological Pathway of Blood Clotting:", "(Make sure you know how each pathway is started and the factors involved and how the", "intrinsic and extrinsic lead to the common pathway, and how fibrin is produced)", "▪", "•", "Clotting is initiated in the extrinsic pathway when Factor VII is activated in the presence", "of tissue factors which are exposed when a cut occurs and are found immediately", "outside the cut site.", "o Factor VIIa then produces a small amount of active factor Xa, which activates a", "small amount of thrombin and results in the formation of a small amount of", "fibrin. The amount of thrombin produced from the extrinsic pathway is too", "small to produce adequate sustained coagulation.", "o This initial small amount of thrombin provides a powerful feedback effect to", "many of the factors of the intrinsic pathway, including factors V, VIII and XI and", "factor XIII. This positive feedback effect of thrombin initiates the further", "formation of thrombin, thereby stimulating its own formation. This activated", "intrinsic pathway produces a large amount of thrombin, and produces a large", "fibrin clot.", "▪ The pathways are activated sequentially with thrombin being the link between them", "Effect of Various Clotting Factor Deficiencies on Clotting:", "▪ A deficiency in factor VII causes serious bleeding", "▪ Individuals that lack factor VIII experience severe bleeding and are known as", "hemophiliacs", "▪ Lack of factor XI causes moderate bleeding", "▪ A lack of factor XII causes no bleeding problem in vivo, but blood does not clot in the", "glass test tube in vitro", "o", "•", "Clotting is not initiated by factor XII, but rather via activation of factor VII", "➢ If a person lacks factor VII there is a serious bleeding problem", "▪ Blood from a healthy individual will clot when placed in a glass test tube with no", "anticoagulant", "o When the blood touches the glass Factor XII is activated and initiates clot", "formation in the glass test tube", "o When the glass is coated by silicon, the surface of the glass becomes too", "smooth to trigger the activation of factor XII. Hence factor XII does not initiate", "the intrinsic pathway.", "What Does Thrombin Do In the Clotting Pathway?:", "▪ Thrombin:", "o Activation of platelets", "o Converts soluble fibrinogen into insoluble fibrin", "o Activates several other clotting factors, including factor V, VIII, XI and XIII", "o Plays a role in anti-clotting pathways (anti-coagulant activity)"] }, { heading: "Lecture 6 recording 19: Mechanisms of Clot Breakdown", id: "lecture-6-recording-19--mechanisms-of-clot-breakdown", items: ["•", "•", "•", "•", "Regulation of Blood Clotting:", "▪ Anticoagulants → prevent clot formation where and when it is not required", "▪ Fibrinolysis → the enzymatic breakdown of the fibrin in blood clots", "Prevention of Clot Formation: Natural Anticoagulants:", "▪ Natural anticoagulants in our body:", "o TFPI or tissue factory pathway inhibitor → inhibits tissue factor, or factor III,", "that is involved in the activation of factor VII.", "➢ Tissue factor (TF = factor III) initiates the extrinsic pathway of clotting as", "it is needed to activate factor VII, which activates factor X", "o Antithrombin 3 → inhibits the actions of thrombin", "o Thrombomodulin → a protein expressed on the surface of undamaged, healthy", "endothelial cells; binds to thrombin to prevent formation of a clot", "➢ Bound thrombin activates inactive protein C to form active protein C.", "Protein C then interacts with protein S, and they inhibit factors Va and", "factor VIIIa.", "❖ Factor Va is involved in the formation of thrombin, while factor", "VIIIa is closely involved in the formation of factor Xa", "Actions of Thrombin As an Anticoagulant:", "▪ Healthy endothelial cells express thrombomodulin", "o Thrombomodulin binds to thrombin and activates protein C", "o Activated protein C inhibits Factors VIIIa and Va", "Prevention of Clot Formation: Clinical Anticoagulants:", "▪ Clinical anticoagulants:", "o Calcium chelators, such as sodium citrate, bind ionized calcium, removing the", "free ionized calcium, and preventing the activation of clotting factors in the", "clotting pathways", "▪ Heparin increases the activity of antithrombin 3", "▪", "•", "•", "•", "Vitamin K antagonists inhibit the synthesis of certain clotting factors that are dependent", "on vitamin K in the clotting pathway (factors II, VII, IX and X)", "Breakdown of Fibrin Clot: Fibrinolysis:", "▪ Fibrinolysis → the breakdown of fibrin in a clot", "▪ Plasminogen activators break down a clot", "o tPA, or tissue plasminogen activator is a plasminogen activator", "o tPA converts inactive plasminogen to the active enzyme plasmin", "o Plasmin then breaks down the insoluble fibrin strands into soluble fibrin", "degradation products to dissolve the clot", "Fibrinolysis:", "▪ Tissue plasminogen activator (tPA)", "o Released from healthy endothelial cells", "▪ Clinical clot busters or thrombolytic drugs", "o Used to treat patients with heart attacks to dissolve clots", "o Thrombolytics work by dissolving a major clot quickly to restart blood flow to", "the heart and helps prevent damage to the heart muscle (do not need to know", "example)", "Abnormal Hemostasis: Imbalance of PRO- and ANTI-hemostatic Factors:", "▪ When pro-hemostatic factors fail:", "o Severe bleeding disorders which lead to hemorrhage may occur", "o Defects in pro-hemostatic pathways may include:", "➢ Problems with the platelets:", "✓ Thrombocytopenia → a deficiency in the numbers of", "platelets", "✓ Abnormal platelet function due to a deficiency of von", "Willebrand’s factor (the plasma protein secreted by", "endothelial cells and platelets that promotes adhesion", "by binding to platelets and exposed collagen molecules", "in damaged blood vessels)", "➢ Problems with clotting factors:", "❖ Hereditary deficiencies of clotting factors", "❖ A number of clotting factors require vitamin K for their synthesis", "and a lack of vitamin K may cause a deficiencies of these factors", "▪ When anti-hemostatic factors fail:", "o Blood clots remain in the circulation for a long time leading to thrombosis", "(formation of blood clot in the vessel, blocking blood flow)", "➢ Deficiencies of natural anticoagulants and fibrinolytic factors due to", "hereditary disorders may cause thrombosis", "➢ Acquired disorders, such as decreased blood flow, may also lead to the", "formation of blood clots"] }, { heading: "Lecture 7 recording 20: Classification of the ABO Blood Groups", id: "lecture-7-recording-20--classification-of-the-abo-blood-grou", items: ["•", "Blood Types: World-wide Distribution in Selected Populations (%):", "▪ Blood types are based on the antigens carried on the surface of red blood cells", "▪", "•", "•", "•", "We will look at the ABO and the Rhesus systems for classifying blood types (you do not", "need to memorize/know this table of blood types in populations…for interest only)", "Antigens of the ABO System of Blood Types:", "▪ The different blood types found in the ABO system are :", "o Group A, B, AB and O", "▪ Antigens of the ABO system present on the surface of red blood cells determine blood", "types", "o The ABO class of antigens are carbohydrate molecules", "o Blood group A has antigen type A on the surface of the red blood cells", "o Blood group B has antigen B on the surface of the red blood cells", "o Blood group AB has both antigens A and B on the surface of the red blood cells", "o Blood group O has no surface antigens of the ABO type on the surface of the red", "blood cells", "▪ Individuals also have plasma (blood) antibodies", "o An antibody is found in the blood and recognizes a unique molecule called an", "antigen; they combine to form an antigen-antibody complex", "o A person with blood type A → has antigen A on the surface of their red blood", "cells; they will not carry anti-A antibody in their plasma, as anti-A antibody", "would recognize antigen A and form an antigen-antibody complex. The", "antibody present in a person with blood type A is anti-B antibody.", "➢ Blood group A → antigen type A, anti-B antibodies", "➢ Blood group B → antigen type B, anti-A antibodies", "➢ Blood group AB → both antigens A and B, no antibodies (no anti-A or", "anti-B antibodies)", "➢ Blood group O → no surface antigens of the ABO type, both anti-A and", "anti-B antibodies", "▪ Remember: antigens found on surface of red blood cells, antibodies found in blood", "What Dictates the Expression of ABO Antigens on RBCs?:", "▪ Genes transfer their specific message from DNA to RNA and then the message is", "translated to form new proteins", "o ABO system, red blood cell surface antigens are carbohydrates, not proteins", "➢ A person with blood type A carries gene A, but gene A does not directly", "code for the surface antigen A because it is a carbohydrate molecule", "❖ Gene A instead codes for the specific enzyme A that allows the", "attachment of the carbohydrate antigen A to protein molecules", "expressed on the surface of red blood cells", "▪ ABO genes code for enzymes (proteins) of the ABO system", "o The enzymes add on the specific carbohydrate molecules to the surface proteins", "of RBCs", "Antigens and Antibodies of the ABO System:", "▪ The genes A and B are dominant over O in heterozygous individuals", "▪ Blood type A - homozygous AA or a heterozygous AO", "▪ Blood type B - homozygous BB or a heterozygous BO", "▪ Blood type AB - AB genotype", "•", "•", "▪ Blood type O - homozygous OO", "How is Blood Type Determined?:", "▪ Blood type is determined by which antigens are present", "▪ A mixture of a sample of RBCs with a solution containing either anti-A or anti-B", "antibodies is observed for RBC agglutination (clumping)", "o Red blood cells of blood type A will clump when anti-A antibody is added, as", "they have the surface antigen A, but will not clump when anti-B antibody is", "added, as there are no surface antigens B present with blood type A", "o Anti-B antibodies will clump cells of blood type B, as the surface antigen B is", "present but there will be no clumping when anti-A antibodies are added", "o With blood type AB, clumping with be observed when either anti-A antibodies", "or anti-B antibodies are added, as both the surface antigen A and B are present", "on the red blood cells", "o With blood type O, no clumping will be observed when either anti-A or anti-B", "antibodies are added, as there are no surface antigens", "What is Agglutination?:", "▪ Agglutination → a process in which the surface antigens on the red blood cells are", "bound to antibodies to form a clump followed by hemolysis, or the rupture or", "destruction of the red blood cells"] }, { heading: "Lecture 7 recording 21: Blood Transfusion ABO Blood Groups", id: "lecture-7-recording-21--blood-transfusion-abo-blood-groups", items: ["•", "•", "•", "ABO Blood Transfusion:", "▪ Blood donors and recipients must be matched before blood is transfused", "Major Cross-match:", "▪ Mismatched combinations of antibodies and antigens would result in agglutination of", "red blood cells and hemolysis", "▪ Major cross match → a test in which a donor’s red blood cell antigens are matched with", "the recipient's plasma antibodies; usually done when a donor’s red blood cells are", "separated from the plasma fraction", "▪ Minor cross match → done when whole blood is transfused where the red blood cells", "are not separated from the plasma, which contains antibodies; the donor’s plasma", "antibodies must also be matched with the recipients red blood cell antigens to prevent", "agglutination", "Blood Transfusion Chart:", "▪ The best donor is the one whose red blood cell antigens match with the recipients blood", "type", "▪ A donor of blood type O can donate blood to recipients with blood type A, B and AB in", "emergency situations", "o Blood donors with blood type O are known as universal donors", "o Donors of blood type O do not possess any red blood cell antigens that can", "cause clumping by reacting with a recipient’s plasma antibodies", "▪ A donor of blood type AB can receive blood from all other ABO blood types in", "emergency situations", "o Blood recipients with blood type AB are known as universal recipients", "o", "•", "Recipients of blood type AB do not possess any plasma antibodies that can", "cause clumping of the donor’s red blood cell antigens", "Mismatched Blood Transfusion:", "▪ When there is a mismatched blood transfusion of the ABO blood types, a transfusion", "reaction characterized by agglutination, or clumping of the red blood cells, and", "hemolysis (rupture of red blood cells) occurs"] }, { heading: "Lecture 7 recording 22: Classification of the Rhesus (Rh) Blood Groups", id: "lecture-7-recording-22--classification-of-the-rhesus--rh--bl", items: ["•", "•", "•", "•", "•", "Classification of the Rhesus (Rh) Blood Type:", "▪ Two types of rhesus blood types: *", "o Rh positive and Rh negative", "o Classification is based on the presence or absence of a protein on the surface of", "red blood cells known as the D antigen", "▪ Rhesus D positive is the predominant rhesus blood type (Rh+)", "Classification of the Rhesus (Rh) Blood Type:", "▪ D antigens found on red blood cell membranes are protein molecules which form an", "integral part of the red blood cell membrane.", "▪ D antigens are coded for by the dominant D genes", "▪ Dominant D gene → presence of the D antigen on red blood cell membrane → Rh+", "▪ No dominant D gene → absence of the D antigen on red blood cell membrane → RhAntigens and Antibodies of the Rh System:", "• Rh+ → either homozygous dominant genotype (DD) or heterozygous genotype (Dd)", "• Rh- → dd, containing two recessive alleles", "• In the Rh system, Rh+ individuals have D antigens on the surface of the red blood cells and", "no anti-D antibodies in plasma", "• Rh- individual lacks D antigens and does not have any anti-D antibodies in plasma", "▪ Exception: when an Rh- person develops anti-D antibodies when they are accidentally", "exposed to D antigens during a blood transfusion or during pregnancy, in the case of an", "Rh- woman. Anti-D antibodies are formed in the same manner by which our immune", "system reacts to exposure to a foreign bacterial antigen in developing antibodies.", "• Anti-D antibodies are of the IgG class, or immunoglobin G", "Mismatched Blood Transfusion in the Rh System:", "▪ During a mismatched transfusion in the Rh system:", "o Rh- person with no anti-D antibodies is exposed accidentally to Rh+ blood during", "transfusion", "o Rh- person develops anti-D antibodies", "o Then the same Rh- person is exposed by mistake to another transfusion of Rh+", "blood", "o Anti-D antibodies will bind to Rh+ RBC and cause clumping and hemolysis", "Rhesus Mismatch Between Mother and Child:", "▪ Rhesus mismatch poses a problem during pregnancy if a woman is Rh▪ If an Rh- woman conceives a child with an Rh+ man, she will carry an Rh+ baby in her", "pregnancy", "▪", "▪", "▪", "▪", "▪", "▪", "During the first pregnancy the mother’s body is not exposed to baby’s Rh antigen as the", "baby grows; baby is healthy", "During delivery rupture of placental blood vessels causes some of the fetal Rh+ red", "blood cells to accidentally enter the maternal blood; this exposes the baby’s Rh+ blood", "to the mother’s immune system", "The mother is sensitized to the Rh antigen and produces anti-D or anti-Rh antibodies", "If the same woman is pregnant with a second Rh+ child, circulating anti-D antibodies in", "the mother’s blood will pass through the placenta into the baby’s body and bind to the", "baby’s red blood cells to cause rupture and hemolysis", "The baby is born with hemolytic disease of the newborn (HDN); HDN babies are born", "with high levels of ruptured red blood cells with enlarged spleens and jaundice due to", "breakdown of hemoglobin", "This condition is prevented by treating the mother immediately after her first delivery", "with anti-Rh antibodies which will bind to all the red blood cells from the Rh+ newly", "delivered baby that have escaped into the mother’s body and are circulating in the", "mother’s blood; the baby’s red blood cells carrying D antigens are bound and blocked by", "anti-D antibodies and are not exposed to the mother's immune system to sensitize her"] }, ], nms: [ { heading: "Lecture 1 recording 1: An Introduction to the Nervous System", id: "lecture-1-recording-1--an-introduction-to-the-nervous-system", items: ["•", "•", "•", "•", "An Introduction to Neuroscience:", "▪ The nervous system is made of the:", "o Central nervous system → brain and spinal cord", "o Peripheral nervous system → nerves that serve the neck and arms, trunk, legs,", "skeletal muscles and internal organs", "The Stretch Reflex:", "▪ The stretch reflex is the simplest stimulus- response paradigm that the human nervous", "system can generate", "▪ Stretch reflex → muscle contraction in response to stretching within muscle", "▪ Patellar-tendon stretch reflex: tap the patellar tendon which attaches to the quadriceps", "muscle → quadriceps muscle stretches, making the quadriceps muscle longer →", "activation of nerve impulses in special receptors (stretch receptors) located in the", "quadriceps muscle → nerve impulses are sent back to the spinal cord along the sensory", "neuron, and activate another nerve cell which feeds back out onto the quadriceps", "muscle, activating this muscle and causing it to contract → a jerk or swing of the foot", "outwards", "The Withdrawal Reflex:", "▪ (This is another reflex we will look at)", "Components of the Nervous System:", "▪ Central nervous system (CNS):", "o Brain and spinal cord", "o Composed of the cerebral cortex, the cerebellum, the brain stem and the spinal", "cord", "o The spinal cord is anatomically similar along its entire extent", "▪ Peripheral nervous system (PNS):", "o Comprised of peripheral nerves, receptors in our muscle in the stretch reflex", "that signal muscle stretch and axons of nerve cells which connect the spinal cord", "to the muscles"] }, { heading: "Lecture 1 recording 2: Cells of the Nervous System and Reflexes", id: "lecture-1-recording-2--cells-of-the-nervous-system-and-refle", items: ["•", "Cells of the Nervous System:", "▪ A neuron is a nerve cell (note a nerve cell is different from a nerve….will look at later)", "▪ 2 types of cells in the nervous system: neurons and glia", "o Neurons make up about 10% of the total number of cells in the CNS but occupy", "50% of the volume (bigger than glia)", "▪ 3 different types of neurons:", "o Afferent neurons → take information from the periphery to the CNS", "o Efferent neurons → take information from the CNS back out to the periphery", "o Interneurons → carry information between neurons", "▪ Afferent neurons and efferent neurons: only activate/excite", "•", "•", "•", "o Afferent neurons make synaptic contact onto either efferent neurons directly or", "they may make excitatory contact onto interneurons", "o Efferent neurons make contact onto muscle (receive input from either afferent", "neurons directly, or from interneurons)", "o Parts of the afferent and efferent neurons are always found in the PNS", "▪ Interneurons can either excite or inhibit other neurons", "o Located entirely within the CNS (not found in the PNS)", "o Interneurons receive input from either afferent neurons or other interneurons", "o Make contact onto either efferent neurons or onto other interneurons", "The Stretch Reflex:", "▪ Hammer tap of the patellar tendon results in muscle stretch → activates the afferent", "neuron → afferent neuron travels to the spinal cord and synapses with an efferent", "neuron → efferent neuron travels back to the periphery and results in the quadriceps", "muscle contraction", "• More Cells of the Nervous System:", "▪ Glia:", "o The glue of the nervous system", "o 90% of the cells in the nervous system and occupy ~ 50% of the volume of the", "nervous system", "o Include: oligodendrocytes, Schwann cells, astrocytes, microglia", "➢ Oligodendrocytes and Schwann cells → make myelin. Oligodendrocytes", "make myelin in the CNS and Schwann cells in the PNS.", "Spinal Cord: Interface for Reflexes:", "▪ Spinal cord has two main components: gray matter and white matter. Gray matter is a", "horn or butterfly shape, and white matter surrounds the horn or butterfly shape.", "▪ When afferent neurons and efferent neurons innervate a muscle, they are separated", "from each other around the muscle", "o The neurons travel towards the CNS within a mixed peripheral nerve or a spinal", "nerve", "o A mixed peripheral nerve contains both afferent fibers and efferent fibers", "o Afferent neurons → carry information from the periphery to the spinal cord via", "the dorsal roots", "o Efferent neurons → carry information from the spinal cord to the periphery via", "the ventral roots", "o Interneurons → carry information between neurons and located entirely within", "the CNS", "Spinal Cord: Interface for Reflexes:", "▪ Afferent information comes in through the dorsal part of the spinal cord and efferent", "information leaves the ventral part of the spinal cord", "▪ Reflex loop:", "o Circular in nature.", "o Activation of a receptor will activate an afferent fiber which enters through the", "dorsal root of the spinal cord. This will activate an efferent fiber which leaves", "through the ventral root of the cord. The efferent fiber will activate a muscle.", "▪", "•", "Myelin", "o Made by oligodendrocytes in the CNS", "o Coats the axons of neurons and allows them to transmit the nerve impulses", "much more quickly", "o Myelinated axons of neurons are found in the white matter of the spinal cord", "o White matter appears white because it contains myelinated axons of neurons", "(myelin gives a white appearance)", "▪ Gray matter contains largely cell bodies of interneurons and unmyelinated processes.", "Due to the lack of myelin, gray matter does not look white.", "The Stretch Reflex:", "▪ Tendon tap of the patellar tendon results in stretching of the quadriceps muscle →", "stretching activates stretch receptors which are connected to afferent neurons →", "information is sent from the muscle back to the spinal cord through the afferent neuron", "indicating that the muscle has been stretched → afferent neuron travels with efferent", "neurons in the mixed peripheral nerve until it gets just outside the spinal cord →", "afferent neuron enters through the dorsal root of the spinal cord and contacts an", "efferent neuron of the ventral part of the cord → efferent neuron exits through the", "ventral root of the spinal cord → efferent neuron travels via the mixed peripheral nerve", "to the quadriceps muscle and results in its contraction", "▪ Interneurons:", "o Involved in the stretch reflex", "o Can be either excitatory or inhibitory", "o Always located entirely within the CNS", "o Interneuron in the stretch reflex is inhibitory. The afferent nerve fiber also", "synapses with an inhibitory interneuron. When activated, the inhibitory", "interneuron inhibits efferent neurons which innervate the hamstrings muscle.", "This inhibits contraction of the hamstrings muscle so that it does not interfere", "with the reflex response."] }, { heading: "Lecture 1 recording 3: Neuron Structure", id: "lecture-1-recording-3--neuron-structure", items: ["•", "Neuron Structure and Polarity:", "▪ A neuron:", "o Is a nerve cell", "o Contains:", "➢ Dendrites → receive information from periphery or from other cells", "➢ Cell body → also called a soma; contains nucleus", "➢ Axon hillock → very initial segment of the axon; integrates/processes", "information coming into the dendrites and generates a nerve impulse if", "there is enough input", "➢ Axon → propagates nerve impulses from initial segment to axon", "terminals", "➢ Axon terminals/synaptic terminals → contains neurotransmitter in", "synaptic vesicles", "▪", "•", "•", "•", "•", "•", "Information in the nervous system flows in one direction only: it flows from dendrites", "and cell bodies down the axon towards axon terminals", "▪ Synapse – junction between 2 neurons", "▪ Presynaptic neuron – the neuron before the synapse", "▪ Postsynaptic neuron – the neuron after the synapse", "Types of Neurons", "▪ Neurons have different morphologies but they have the same ‘parts’ (dendrites, cell", "body, axon, axon terminals)", "▪ Afferent neuron in stretch reflex is a pseudo-unipolar cell", "The Stretch Reflex", "▪ Afferent neuron of stretch reflex:", "o Sensory neuron which takes information from muscle stretch to the CNS", "o Pseudo-unipolar cell", "o Cell body located in dorsal root ganglion", "o Peripheral axon – extends from the cell body to the muscle", "o Central axon – from cell body into CNS and makes contact with other neurons", "Neuron Structure", "▪ Myelinated axon – allows nerve impulses to move more quickly", "Neuron Structure", "▪ (This is a summary slide of the structure of a neuron. We will continue to look at the", "different parts of the neuron and talk about them in more detail)", "The Stretch Reflex", "▪ Afferent neuron:", "o Pseudo-unipolar cell", "o Peripheral axon of the afferent neuron extends to the muscle and receives", "stretch input from the quadriceps muscle", "o Central axon of the afferent neuron arises from the cell body and extends to the", "CNS", "o Makes two synapses, or two contacts, onto other neurons (the efferent neuron", "to quadriceps muscle and an inhibitory interneuron)", "➢ Afferent neuron makes direct monosynaptic contact onto the efferent", "neuron which innervates the quadriceps muscle", "❖ The excitatory efferent neuron which travels to the quadriceps", "muscle is activated, resulting in contraction of the quadriceps", "➢ Afferent neuron synapses with an inhibitory interneuron", "❖ The afferent neuron is excitatory and activates an inhibitory", "interneuron. The inhibitory interneuron makes contact onto an", "efferent neuron which innervates the antagonistic muscle,", "which is the hamstring.", "❖ Contact onto the inhibitory interneuron inhibits the efferent", "neuron travelling to the hamstrings muscle and inhibits the", "hamstrings muscle from contracting.", "▪ When the quadriceps muscle is stretched by tapping the patellar tendon, the quadriceps", "muscle is activated to contract, while contraction of the hamstrings muscle is inhibited", "▪", "Interneurons and the two efferent neurons to the quadriceps and hamstrings muscles", "are multipolar cells:", "o Dendrites emanate from the cell body", "o The multipolar neurons have an axon whose axon terminals terminate in the", "muscle, affecting activity of the muscle"] }, { heading: "Lecture 2 recording 4: The Resting Membrane Potential", id: "lecture-2-recording-4--the-resting-membrane-potential", items: ["•", "•", "•", "•", "Membrane Structure:", "▪ Neuron plasma membrane:", "o Phospholipid bilayer", "o Contains protein pumps and channels:", "➢ Which set resting membrane potential of the cell (the neuron)", "➢ Which allow and control movement of ions into and out of the cell", "➢ Pumps – active transport; use an energy source to pump ions across the", "membrane", "➢ Ion channels – do not use an energy source and are not active transport;", "allow ions to flow through down an electrochemical gradient", "❖ Passive channels – these are leak channels; always open and", "selective for a given ion", "❖ Gated channels – require a stimulus to open the channel and", "allow ions to flow through", "✓Ligand-gated and voltage-gated channels", "Resting Membrane Potential (Em)", "▪ Resting membrane potential – a measure of the electrical potential difference between", "the intracellular environment and the extracellular environment", "o Charge separation between the inside and outside of the cell", "o At steady state, this charge separation is the resting membrane potential", "▪ Resting membrane potential is ~ -70 mV (not the same for every cell!)", "o Most important ions involved in setting the resting membrane potential: sodium", "(Na+) and potassium (K+)", "➢ Chloride and organic anions play a minor role", "o Pumps/channels involved in setting resting membrane potential: Na+/K+ pump,", "Na+ leak channels, K+ leak channels", "➢ Chloride pump plays minor role", "Resting Membrane Potential (Em)", "▪ Na+/K+ pump – active transporter involved in setting resting membrane potential", "Net Negative Charge is Set by the Na+/K+ pump", "▪ Na+/K+ pump", "o Electrogenic :", "➢ Moves charge across the membrane", "➢ 3 positively charged Na+ ions are pumped out of the cell for every 2", "positively charged K+ ions brought into the cell, moving a net of 1", "positively charged ion out of the cell for every cycle of the Na+/K+ pump,", "resulting in a net negative charge inside the cell", "•", "o Uses energy from ATP hydrolysis/breakdown (ATP → ADP + Pi)", "Na /K Pump Creates Gradients", "▪ Within a cell there are:", "o Chemical gradients for Na+ and K+", "o Electrical gradients (inside cell more negative than outside)", "▪ Na+/K+ pump", "o Creates the Na+ and K+ chemical gradients", "o Na+ outside cell > Na+ inside cell (Na+ wants to diffuse into cell and Na+ pumped", "out by Na+/K+ pump)", "o K+ inside cell > K+ outside cell (K+ wants to diffuse out of cell and 2 K+ pumped in", "by Na+/K+ pump)", "▪ Electrical gradient", "o Due to electrogenic nature of Na+/K+ pump, inside of cell more negative than", "outside", "+", "+"] }, { heading: "Lecture 2 recording 5: How is the Resting Membrane Potential Set?", id: "lecture-2-recording-5--how-is-the-resting-membrane-potential", items: ["•", "•", "•", "•", "Resting Membrane Potential (Em):", "▪ Na+/K+ pump sets up an unequal distribution of Na+ and K+ ions across the cell", "membrane.", "▪ Na+ and K+ ions will try to achieve a state of equilibrium through the leak channels", "Em is Set by Leak Channels:", "▪ Leak channels:", "o Always open", "o Allow the passive flow of ions into/out of neuron", "o Selective for an ion", "o Ions move through based on electrical and chemical gradients", "Em is Set by Leak Channels:", "▪ K+ concentration inside cell > K+ concentration outside cell (concentration gradient set", "by Na+/K+ pump)", "▪ Chemical force pushes K+ out of the cell through K+ leak channels", "▪ Electrical force pushes K+ into the cell through K+ leak channels", "▪ Chemical and electrical forces act on K+ at the same time in opposite directions", "▪ Equilibrium potential → the electrical potential at which K+ is completely at equilibrium", "o Equilibrium potential for K+ = -90 mV", "▪ Remember: resting membrane potential is -70 mV", "o What will K+ be doing at the resting potential?", "o K+ will move out of the cell, taking with it positive charge, to try to move the", "resting membrane potential towards its equilibrium potential of -90 mV", "Em is Set by Leak Channels:", "▪ Na+ concentration outside cell > Na+ concentration inside cell (concentration gradient", "set by Na+/K+ pump)", "▪ Chemical force pushes Na+ into the cell through Na+ leak channels", "▪ Electrical force pushes Na+ into the cell through Na+ leak channels", "▪ Chemical and electrical forces act on Na+ at the same time", "▪", "•", "•", "Equilibrium potential → the electrical potential at which Na+ is completely at", "equilibrium", "o Equilibrium potential for Na+ = +55 mV", "▪ Remember: resting membrane potential is -70 mV", "o What will Na+ be doing at the resting potential?", "o Na+ will move into the cell, taking with it positive charge, to try to move the", "resting membrane potential towards its equilibrium potential of +55 mV", "Em is Set by Leak Channels:", "▪ In an actual nerve cell, both Na+ and K+ are present", "▪ How is the resting membrane potential of -70mV achieved?", "o The more permeable the membrane is to a given ion, the closer the resting", "membrane potential of that cell will be to that given ion’s equilibrium potential", "Em is Set by Leak Channels:", "▪ The more permeant the ion, the greater its ability to force Em towards its own", "equilibrium potential", "o How is a membrane more permeable to an ion? By having more channels for", "that ion:", "❖ There are more leak channels for K+ than there are for Na+ in the", "membrane and the membrane is therefore more permeable to K+", "✓ The resting membrane potential (Em) is closer to the equilibrium", "potential for K+ than for Na+ as there are more K+ leak channels", "in the membrane compared to Na+ leak channels", "▪ Why do different cells have different resting membrane potentials? Cells have different", "ratios of K+ leak channels to Na+ leak channels"] }, { heading: "Lecture 2 recording 6: Review of the Resting Membrane Potential", id: "lecture-2-recording-6--review-of-the-resting-membrane-potent", items: ["•", "Review of Resting Membrane Potential (Em):", "▪ Activity of the Na+/K+ pump creates an intracellular environment that is more negatively", "charged with respect to the extracellular environment", "▪ Leak channels allow diffusion of ions down their electrical and chemical concentration", "gradients in an attempt to reach their own equilibrium potentials", "▪ K +:", "o The electrical force pushes K+ into the cell while the chemical force pushes K+", "out of the cell", "o K+ will move to try to achieve a membrane potential closer to its equilibrium", "potential of -90mV", "o If the resting membrane potential of cell is not at -90 mV, K+ will leave the cell", "to try to bring the resting membrane potential closer to -90 mV.", "+", "▪ Na :", "o The electrical force and the chemical force push Na+ into the cell.", "o Na+ will move to try to achieve a membrane potential closer to its equilibrium", "potential of +55mV", "o At a resting membrane potential of -70 mV, Na+ will move into the cell, trying to", "bring the cell closer to +55 mV", "•", "•", "Review of Resting Membrane Potential (Em):", "▪ At resting membrane potential passive ionic fluxes are balanced so that there is charge", "separation and Em remains constant", "▪ Value of resting membrane potential (-70 mV) is closest to equilibrium potential of ion", "with greatest membrane permeability: this ion is always K+", "Events at the Neuron Cell Membrane", "▪ Resting membrane potential is -70mV due to Na+/K+ pump and leak channels", "▪ At a constant or resting membrane potential we do have the movement of ions, Na+ and", "K+, across the cell membrane. K+ is being pumped in by the Na+/K+ pump and is leaving", "through the K+ leak channels. Na+ is being pumped out by the Na+/K+ pump and coming", "back into the cell through the Na+ leak channels."] }, { heading: "Lecture 3 recording 7: How is the Action Potential Generated?", id: "lecture-3-recording-7--how-is-the-action-potential-generated", items: ["•", "The Stretch Reflex:", "This section discusses how stretch of the quadriceps muscle results in generation of an", "action potential in the afferent neuron", "•", "Action Potentials:", "▪ The resting membrane potential is a steady-state condition determined by the relative", "permeability of the membrane to K+ and Na+", "o When the patellar tendon is tapped, all the neurons in the stretch reflex", "(afferents, efferents and interneurons) are at resting membrane potential", "▪ Specific stimuli disrupts the steady state-by causing ion selective channels in the", "membrane to open", "o In the stretch reflex, the physical stimuli is a stretching of the quadriceps muscle", "▪ 2 main types of ion channels (other than the leak channels) in a neuron:", "o Voltage-gated ion channels", "❖ Opened at a specific membrane voltage", "o Ligand-gated ion channels", "❖ Involved in neurotransmitter release and synaptic transmission", "▪ An electrical signal, known as an action potential, is generated due to the activity of", "voltage-gated Na+ and voltage-gated K+ channels", "▪ Action potential → large change of membrane potential from the resting membrane", "potential of ~ -70 mV and to ~ +30mV, approaching the equilibrium potential of Na+", "(ENa= +55mV)", "o Membrane potential does not quiet reach the Na+ equilibrium potential", "o Membrane potential then falls back to the resting membrane potential of", "-70mV over a period of a few milliseconds (~2 to 3 milliseconds)", "▪ Resting Membrane Potential (Em):", "o Neurons are surrounded by a phospholipid bilayer", "o Within bilayer are the pumps and ion channels (passive and gated channels)", "▪ How Are Afferents Activated?:", "o Afferent neuron embedded in the quadriceps muscle has a sensory receptor", "❖ Senses muscle stretch", "▪", "o Muscle stretch (stretch reflex) or other sensory stimuli results in increased", "opening of specialized Na+ receptors, entry of Na+ into afferent fiber and", "depolarization of afferent neuron", "❖ Muscle stretch = enlargement of sensory receptor and movement of Na+", "ions through pores in the sensory receptor", "❖ Slight depolarization of the membrane potential occurs due to the", "inward movement of positively charged Na+", "o There is a value of membrane potential in the cell which is called ‘threshold’;", "this value is the threshold for the opening of the voltage-gated Na+ channels and", "the threshold for firing of an action potential", "❖ Threshold is typically 10 to 15 mV more depolarized than resting", "membrane potential (we will use -50mV as threshold)", "❖ If Na+ entry is sufficient to depolarize the neuron to its threshold (~-50", "mV) the result is the opening of voltage-gated Na+ channels and an", "action potential", "✓ When voltage-gated Na+ channels open, permeability of the cell", "to Na+ increases greatly (ie. LOTS of Na+ moves through the", "voltage-gated Na+ channels very quickly)", "Voltage-gated Ion Channels:", "o Note: Leak channels are open at resting membrane potential but voltage-gated", "Na+ channels and voltage-gated K+ channels are closed at rest", "o At rest, the outside of the cell is positively charged with respect to the inside (ie.", "the inside is negatively charged at rest)", "o Tap of patellar tendon → stretches quadriceps muscle → Na+ enters cell", "following stretch of the sensory receptor → slight depolarization of the cell due", "to Na+ moving into cell (membrane potential becomes more positive) → if", "threshold is reached (-50mV) voltage-gated Na+ channels open → at threshold,", "the activation gate is removed allowing Na+ to flow into cell → influx of Na+ into", "cell brings membrane potential closer to Na+ equilibrium potential → internal", "compartment of cell changes from negatively charged to positively charged", "(+30mV) → around +30mV the inactivation gate closes Na+ channel and Na+", "cannot enter cell → activation gate of voltage-gated K+ channel is removed and", "K+ leaves cell removing positive charge → efflux of K+ moves cell closer to the K+", "equilibrium potential and the cell repolarizes", "o Open conformation of the voltage-gated Na+ channels is only maintained for a", "few ms"] }, { heading: "Lecture 3 recording 8: Phases of the Action Potential", id: "lecture-3-recording-8--phases-of-the-action-potential", items: ["•", "The Action Potential (2 slides):", "Understand the phases of the action potential and the events that occur during each phase", "(ie. which channels are involved, which ions are involved, what is the permeability to the", "ions or are the ion channels open or closed; see powerpoint file “Summary of Nerve-muscle", "Action Potential)", "▪", "•", "The membrane potential of the cell is the result of the relative permeability of that cell", "to Na+ and K+.", "o The resting membrane potential is entirely determined by the leak channels; at", "rest the membrane is more permeable to K+ than Na+", "o During the action potential, voltage-gated Na+ channels and voltage-gated K+", "channels open and close during the different phases", "▪ Voltage-gated Na+ channels:", "o Can be closed (or in “resting state”), open or inactivated", "o In the inactivated state the Na+ channel is closed and cannot be opened, even", "with stronger stimuli. In order to open the Na+ channel, it must return to the", "‘closed’ state again.", "▪ Refractory period – absolute refractory period and relative refractory period", "o Absolute refractory period – time during which an excitable membrane cannot", "generate an action potential in response to any stimulus; due to inactivation of", "voltage-gated Na+ channels", "o Relative refractory period - time during when an excitable membrane will", "generate an action potential but only to a stimulus of greater strength than the", "usual threshold strength", "Membrane Conductance:", "▪ Conductance (g) – rate of ion travel through a channel", "▪ Depolarization phase – Na+ conductance increases due to opening of voltage-gated Na+", "channels; conductance decreases as voltage-gated Na+ channels inactivate", "▪ Repolarization phase – K+ conductance increases due to the opening of the voltagegated K+ channels; conductance decreases as voltage-gated K+ channels close"] }, { heading: "Lecture 3 recording 9: Action Potentials: Transmission", id: "lecture-3-recording-9--action-potentials--transmission", items: ["•", "•", "The Stretch Reflex:", "▪ The movement of an action potential along a neuron is related to the relative", "permeabilities of Na+ and K+", "Action Potentials: Transmission (3 slides):", "▪ At rest inside the cell/neuron - negatively charged; outside the cell - positively charged.", "▪ Step 1: Axon at resting membrane potential:", "o -70 mV", "o Voltage-gated Na+ channels are closed", "▪ Step 2: Activation results in opening of voltage-gated Na+ channels:", "o Activation of the stretch receptor results in a small amount of Na+ entering the", "axon; this will bring this segment of the axon to threshold, resulting in the", "opening of the voltage-gated Na+ channels and the generation of an action", "potential, where the inside of the axon reaches ~+30 mV", "▪ Step 3: Local depolarization of membrane causes adjacent voltage-gated Na+ channels", "to activate", "o The opening of the voltage-gated Na+ channels causes a local depolarization in a", "segment of the axon", "▪ Step 4: New action potential is generate in adjacent membrane", "•", "•", "o The action potential is transmitted from segment to segment along the axon by", "local depolarization of the neighboring membrane", "▪ Step 5: Action potential only travels in one direction due to refractory period", "Action Potentials: An Animation:", "▪ During an action potential the inside of the cell membrane becomes positive with", "respect to the outside", "▪ An action potential generates local currents which depolarize the membrane", "immediately adjacent to the action potential", "▪ When depolarization caused by the local currents reaches threshold, a new action", "potential is produced adjacent to the original one", "▪ Action potential propagation occurs in one direction only due to refractory period", "Electrotonic Conduction:", "▪ Electrotonic conduction → spread of current inside axon", "▪ Summary:", "o Patellar tendon tap activates the stretch receptor located within the muscle", "o Na+. enters the cell through stretch receptors, bringing it to threshold and", "generating an action potential", "o AP initiated at one point in membrane", "o Current spreads electrotonically to adjacent membrane", "o Adjacent membrane depolarizes to threshold", "o New AP generated in adjacent membrane", "▪ Electrotonic conduction proceeds in one direction only due to refractory period", "o Following an action potential the voltage-gated Na+ channels which opened for", "the action potential will inactivate and must recover from this inactivation", "before they can open again"] }, { heading: "Lecture 4 recording 10: Electrotonic Conduction and Myelination", id: "lecture-4-recording-10--electrotonic-conduction-and-myelinat", items: ["•", "•", "•", "•", "Electrotonic Conduction:", "(Review of electrotonic conduction)", "Electrotonic Conduction:", "▪ The process of electrotonic conduction involves many steps, but an action potential", "would have to be regenerated at every point on the membrane for an impulse to travel", "from point A to point B along a neuron", "▪ How can the speed of action potential propagation (electrotonic conduction) be", "increased?", "o Myelination", "Cells of the Nervous System:", "▪ Glia include oligodendrocytes and Schwann cells", "▪ Myelin:", "o Made by oligodendrocytes in the central nervous system and Schwann cell in", "the peripheral nervous system", "Myelination:", "▪ Lipid-protein mix", "▪ An axon is wrapped with myelin, a process called ensheathing the axon", "▪", "Acts as an insulator and does not allow ions to move across axon where the myelin is", "present"] }, { heading: "Lecture 4 recording 11: Nodes of Ranvier", id: "lecture-4-recording-11--nodes-of-ranvier", items: ["•", "•", "Nodes of Ranvier:", "▪ Axon is the only part of a neuron that is myelinated (no myelin on cell body or", "dendrites; myelin stops just before axon terminals)", "▪ Nodes of Ranvier:", "o Regions of a myelinated axon which are unmyelinated", "o Myelination is discontinuous along the axon", "o Contain the voltage-gated Na+ channels (ie. voltage-gated Na+ channels are not", "found along the axon in the myelinated regions)", "❖ Voltage-gated Na+ channels are also found clustered at the axon hillock,", "which is unmyelinated", "Nodes of Ranvier:", "▪ In the peripheral nervous system: a single Schwann cell myelinates one segment of the", "axon", "▪ In the central nervous system: a single oligodendrocyte myelinates several axons and", "several regions within a given axon"] }, { heading: "Lecture 4 recording 12: Saltatory Conduction and Speed of Propagation", id: "lecture-4-recording-12--saltatory-conduction-and-speed-of-pr", items: ["•", "•", "Saltatory Conduction:", "▪ Propagation of action potentials along a myelinated axon such that the action potentials", "jump from one node of Ranvier in the myelin sheath to the next", "▪ Is electrotonic conduction at the node of Ranvier", "▪ Due to the presence of myelin, the neighbouring tissue is not depolarized at every point", "along an axon", "o The action potential is generated at the first node of Ranvier and then passes to", "the second node of Ranvier, where the process of depolarizing the neighboring", "tissue will then occur. The action potential can pass undiminished in size from", "node of Ranvier to node of Ranvier.", "o It is only at the nodes of Ranvier that depolarization of the neighbouring tissue", "and the opening of the voltage-gated sodium channels occurs", "Classification of Afferent Fiber Type:", "(You do not need to memorize the 4 types of fibers and diameters and speeds of conduction", "for the Nerve/muscle/synapse section. The key points for this slide are listed below:)", "▪", "•", "2 factors which determine the speed at which an axon propagates along axon potential", "from point A to point B:", "o Size of the axon: the thicker the axon is in diameter, the faster it can propagate", "an action potential", "o Myelination: myelinated axons propagate action potentials faster than", "unmyelinated axons", "Speed of Propagation:", "▪", "▪", "By the time the absolute refractory period of any neuron, whether myelinated or", "unmyelinated, has been completed, the action potential has travelled far enough down", "the axon that there will not be depolarization of the neighbouring tissues ‘upstream’", "The axon potential will always travel down the axon to the synaptic terminals or the", "axon terminals"] }, { heading: "Lecture 4 recording 13: Synaptic Transmission", id: "lecture-4-recording-13--synaptic-transmission", items: ["•", "•", "Synaptic Transmission:", "▪ The process whereby one neuron (nerve cell) communicates with other neurons or", "effectors, such as a muscle cell, at a synapse", "▪ Stretch reflex:", "o Afferent neuron:", "❖ Myelinated – action potential travels by saltatory and electrotonic", "conduction to spinal cord along afferent neuron", "o Afferent neuron activates the efferent neuron (to the quadriceps) and the", "inhibitory interneuron (inhibits efferent neuron to hamstrings) via chemical", "synaptic transmission", "Synaptic Transmission:", "(Shows figures for chemical and electrical synaptic transmission)", "•", "•", "•", "Electrical Synapses:", "▪ Electrical synapse", "o Physical connection between 2 cells which are very close together, allowing the", "passage of ions and small molecules", "o Connexin:", "❖ Protein channel connecting the 2 cells; each connexin made up of 6", "connexin subunits", "❖ Can be open or closed", "o Bidirectional", "o Fast communication between 2 cells", "Chemical Synapses:", "▪ Involves a presynaptic cell and a post-synaptic cell with no physical connection", "▪ Do not have bidirectional transmission – transmission from presynaptic cell to", "postsynaptic cell only", "Chemical Synapses:", "▪ Definitive gap called the synaptic cleft or the synaptic gap between the presynaptic cell", "and the postsynaptic cell", "o As there is no physical connection between the presynaptic and postsynaptic", "cell, the presynaptic cell excites or inhibits the postsynaptic cell by release of a", "neurotransmitter", "▪ Neurotransmitter is stored in the presynaptic terminal in synaptic vesicles", "▪ Neurotransmitter is released from the vesicles and enters into the synaptic gap and", "binds to receptors on the postsynaptic cell", "▪", "Binding of neurotransmitter to receptors on the postsynaptic cell opens ion channels on", "the postsynaptic membrane, resulting in depolarization or hyperpolarization", "o Depolarization or hyperpolarization of the postsynaptic cell is based on which", "neurotransmitter is in the synaptic vesicles", "❖ Neurotransmitters are inhibitory or excitatory"] }, { heading: "Lecture 5 recording 14: More on Chemical Synapses", id: "lecture-5-recording-14--more-on-chemical-synapses", items: ["•", "•", "•", "Chemical Synapses:", "▪ Neurotransmitter is located inside vesicles in the presynaptic terminals", "▪ Receptors for this neurotransmitter are found on the postsynaptic cell", "Resting Membrane Potential (Em)", "▪ Neurotransmitter binds to ligand-gated ion channels at the chemical synapse", "o 2 types of chemical synaptic transmission: directly gated and indirectly gated", "synaptic transmission", "Chemical Synapses: Directly Gated", "▪ Neurotransmitters:", "o Excitatory – glutamate; released by excitatory neurons", "o Inhibitory – glycine or GABA; released by inhibitory neurons", "▪ Neuron is either excitatory or inhibitory; it cannot be both", "▪ Directly-gated chemical synaptic transmission:", "o Neurotransmitter (NT) is released from vesicles in the presynaptic terminal", "o Neurotransmitter crosses the synaptic cleft/gap (~40 nanometers) and binds to", "receptors on the postsynaptic membrane", "o In directly gated chemical transmission the receptor is located on an ion channel", "❖ Neurotransmitter binding to its receptor opens the ion channel", "❖ Ions pass through the channel", "❖ Glutamate is an excitatory neurotransmitter that opens a Na+ channel", "when it binds to a receptor on the postsynaptic cell", "✓ Na+ will flow down its gradient into the cell, making the cell", "more positively charged (the equilibrium potential for Na+ is +55", "mV). This will result in a depolarization of the membrane in the", "postsynaptic cell.", "❖ GABA and glycine are inhibitory neurotransmitters that open a chloride", "channel or a potassium channel when they bind to their receptor on the", "postsynaptic cell.", "✓ When a chloride channel or potassium channel opens this will", "make the inside of the cell more negative. This will result in a", "hyperpolarization of the membrane in the postsynaptic cell.", "i. If potassium channels have opened, potassium will", "leave the cell, taking with it positive charge", "ii. If chloride channels have opened, chloride will enter the", "cell, bringing with it negative charge", "o An action potential is not generated in the postsynaptic cell as threshold not", "reached:", "•", "•", "❖ Excitatory NT → depolarizes postsynaptic membrane → EPSP", "❖ Inhibitory NT → hyperpolarizes postsynaptic membrane → IPSP", "o Effects are fast in onset and short lasting (msec) receptor and the effecter are", "the same molecule", "❖ Receptor is located directly on the ion channel", "Chemical Synapses: Indirectly Gated", "▪ Receptor and the effecter are not the same protein", "▪ Neurotransmitter binds to receptor and activates 2nd messenger system in the", "postsynaptic cell (via G-proteins; GTP activates adenylyl cyclase which converts ATP into", "cAMP, the 2nd messenger)", "▪ cAMP activates protein kinases which phosphorylate a channel and cause it to open or", "close, causing changes in membrane permeability", "o Ions flow, resulting in depolarization or hyperpolarization", "▪ Slow onset and long lasting", "Chemical Synapses versus Electrical Synapses", "▪ Electrical synapses:", "o Inflexible", "o Coordinate the firing of many neurons at the same time", "o Are always excitatory", "▪ Chemical synapses:", "o Provide flexibility", "o Only synapses which can generate inhibition (use inhibitory neurotransmitters", "GABA and glycine)", "o Specific neurotransmitters have specific effects on the postsynaptic membrane", "o Complexity can vary as synaptic transmission can be directly-gated or indirectlygated", "o Time course can vary", "o Plasticity - refers to the process of indirectly-gated chemical synaptic", "transmission where long term changes in neurons are seen"] }, { heading: "Lecture 5 recording 15: Synaptic Transmission: Excitatory versus Inhibitory", id: "lecture-5-recording-15--synaptic-transmission--excitatory-ve", items: ["•", "•", "Neuron Structure and Polarity:", "▪ Directly gated chemical synaptic transmission: direction of information flow is from", "presynaptic cell to postsynaptic cell", "Synaptic Transmission:", "▪ An action potential is generated in the presynaptic neuron and travels down the neuron", "via electronic saltatory conduction (myelinated axon)", "▪ When the action potential arrives at the presynaptic terminal, the presynaptic terminal", "depolarizes", "o The cell changes from negatively charged inside to positively charged inside", "▪ Voltage-gated calcium channels in the presynaptic membrane open due to", "depolarization of the presynaptic membrane", "▪ Calcium enters the cell through the voltage-gated calcium channels and causes vesicles", "containing neurotransmitter to move to and fuse with the presynaptic membrane", "▪", "•", "•", "Neurotransmitter is relealed into the synaptic gap or synaptic cleft by exocytosis from", "the vesicles once they have fused with the presynaptic membrane", "▪ Neurotransmitter diffuses across the synaptic cleft to bind to a ligand-gated ion channel", "(neurotransmitter binds to receptors which are located directly on ion channels in the", "postsynaptic membrane)", "▪ If it is an excitatory neurotransmitter (ie glutamate), the channels would be Na+", "channels", "o The binding of glutamate opens the Na+ channels and Na+ flows through to", "depolarize the postsynaptic cell", "o An EPSP, or excitatory post-synaptic potential, is generated", "▪ If it is an inhibitory neurotransmitter (ie GABA, glycine), the channels would be K+ or Clchannels", "o The binding of GABA or glycine opens the ion channels. Ions (K+ or Cl-) move to", "hyperpolarize the cell", "o If it is a K+ channel, K+ leaves the cell. If it is a Cl- channel, Cl- enters the cell.", "o An IPSP, or an inhibitory post-synaptic potential, is generated", "▪ Neurotransmitter is released from its receptor and is either recycled or degraded", "Presynaptic Neuron Can Be Excitatory:", "▪ Glutamate binds to receptor and opens ligand-gated Na+ channels", "▪ Na+ enters postsynaptic cell and results in small depolarization known as excitatory", "postsynaptic potential (EPSP)", "▪ EPSPs are subthreshold – it will move membrane potential towards threshold but one", "EPSP alone is not enough to generate and action potential", "Presynaptic Neuron Can Be Inhibitory:", "▪ Inhibitory transmitters (GABA, glycine) bind to receptor and opens ligand-gated Clchannels (may also be K+ channel)", "▪ Cl- enters postsynaptic cell (K+ would leave the cell) and results in small", "hyperpolarization known as inhibitory postsynaptic potential (IPSP) and prevents", "generation of action potentials by moving cell away from threshold"] }, { heading: "Lecture 5 recording 16: Synaptic Integration", id: "lecture-5-recording-16--synaptic-integration", items: ["•", "•", "Neuron Structure and Polarity:", "▪ How do EPSPs and IPSPs result in an action potential in the post-synaptic cell? This", "process is called synaptic integration", "Synaptic Potentials Decay with Distance:", "▪ Synaptic potentials are largest at the synapse where they originate", "▪ Synaptic potentials (both EPSPs and IPSPs) decay as they travel away from the synapse", "along the neuronal membrane (decay with distance); they can only travel short", "distances as a result", "o Action potentials do not decay with distance", "▪ Dendrites are not myelinated and have no voltage-gated Na+ channels", "▪ When an EPSP is generated in the post-synaptic membrane, depolarization of", "neighboring tissue can occur in both directions, both away from the cell body and", "•", "•", "towards the cell body. The main point of depolarization is at the synapse between the", "pre-synaptic terminal and the post-synaptic cell.", "Chemical Synapses:", "▪ Synaptic potentials (EPSPs and IPSPs) ~ 0.2mV in magnitude and decay as they travel", "away from the synapse", "PSPs Summate:", "▪ How do the synaptic potentials generate enough depolarization to bring the cell to", "threshold and generate an action potential as they are only 0.2mV in magnitude each", "and decay as they travel?", "o Answer: Summation of postsynaptic potentials or synaptic integration", "▪ Many post-synaptic potentials are generated at any given time and they are additive", "▪ 2 types of summation: temporal summation and spatial summation", "o Temporal summation – occurs when multiple postsynaptic potentials from a", "single presynaptic neuron arrive at the cell body at a given point in time (single", "presynaptic neuron fires many times in succession)", "o Spatial summation – occurs when multiple postsynaptic potentials from", "different presynaptic neurons arrive at the cell body at the same time (different", "locations at the same time)", "▪ A cell body may receive both excitatory and inhibitory presynaptic terminals", "o EPSPs and IPSPs may be generated on the cell body at the same time- they will", "add together and may cancel each other out (EPSPs are positive and IPSPs are", "negative)"] }, { heading: "Lecture 5 recording 17: Synaptic Integration", id: "lecture-5-recording-17--synaptic-integration", items: ["•", "•", "More On Synaptic Integration:", "▪ Integration: process of summing together all the inputs into a pattern of action potential", "output in the postsynaptic cell", "▪ The axon hillock constantly calculates the total amount of excitation and the total", "amount of inhibition; it integrates all the inputs", "o If the integrated number is high enough, the cell will be brought to threshold,", "and the voltage-gated Na+ channels will open and the cell will fire an action", "potential. The action potential will then travel down the axon to the synaptic", "terminals.", "o If the integrated number is not high enough, the cell will not reach threshold", "and an action potential will not occur", "▪ All of the inputs, both excitatory or inhibitory reaching the axon hillock at any given", "time, determine whether the cell hits threshold", "PSPs Summate (2 slides):", "(These slides go through an integration problem. Key is that all the PSPs, either EPSPs or", "IPSPs, summate. This determines the change in membrane potential and whether a cell", "reaches threshold or not. EPSPs bring cells closer to threshold and IPSPs move cells further", "from threshold)", "•", "Complexity of Behavior:", "▪", "▪", "•", "Synaptic integration increases complexity of behavior", "The exact same stimulus in two different situations can generate two completely", "different responses; the reason for this is either an increase or decrease of inhibition of", "excitation of the different neurons within a pathway", "Comparison of PSPs and APs:", "▪ It compares post-synaptic potentials and action potentials.", "▪ Amplitude:", "o Post-synaptic potentials: small, depolarizing or hyperpolarizing", "o Action potentials: always the same size, only depolarizing (they are never", "hyperpolarizing), all-or-none (if the strength of the stimulus exceeds the", "threshold potential, the nerve will give a complete response; there is no", "response if threshold is not exceeded)", "▪ Duration:", "o Postsynaptic potentials have a longer duration than action potentials (Action", "potentials ~ 2 to 3 milliseconds; Postsynaptic potentials ~ 10-20 milliseconds to", "a few seconds in duration)", "▪ Location:", "o Postsynaptic potentials are mostly evoked on dendrites or the soma as this is", "where the synapse is located between the presynaptic neuron and the", "postsynaptic neuron", "o Action potentials are initiated at the axon hillock or the initial segment of the", "axon and transmitted down the axon to the synaptic terminals", "▪ Conduction:", "o Postsynaptic potentials are passive, travel short distances and decrease in", "amplitude as they travel", "o Action potentials are active, travel long distances and are regenerated at every", "point. In a myelinated axon, the action potentials are regenerated at every", "node of Ranvier back to their initial amplitude. In an unmyelinated axon, they", "remain at their initial amplitude due to the opening of the voltage-gated Na+", "and K+ channels.", "▪ Function:", "o Postsynaptic potentials function to change the electrical potential of the", "postsynaptic neuron,", "❖ A depolarizing synapse with an excitatory neurotransmitter", "(glutamate)moves the potential closer to threshold", "❖ A hyperpolarizing synapse with an inhibitory neurotransmitter (GABA or", "glycine) moves the potential further away from threshold", "❖ Postsynaptic potentials trigger action potentials when the axon hillock is", "depolarized to the threshold value.", "o Action potentials are simply generated if threshold is reached and will travel to", "the synaptic terminals to initiate neurotransmitter release"] }, { heading: "Lecture 6 recording 18: Muscle", id: "lecture-6-recording-18--muscle", items: ["•", "•", "Neuron Structure and Integrity:", "▪ This section looks at the efferent neuron, or motor neuron, of the quadriceps muscle", "and how an action potential travels down, releases neurotransmitter at the synaptic", "terminals and results in an actual physical muscle contraction", "3 Types of Muscle (2 slides):", "(Only need to know the properties of skeletal muscle for this section. Other sections will", "look at cardiac muscle and smooth muscle)", "▪", "▪", "•", "3 types of muscle: skeletal muscle, cardiac muscle and smooth muscle", "Skeletal muscle:", "o Muscle attached to the skeleton", "o Also called striated muscle", "o Contraction is under voluntary control", "Skeletal Muscle:", "▪ Each muscle consists of a number of muscle cells or muscle fibers which run lengthwise", "along the muscle", "▪ Each muscle cell is surrounded by endomysium ( a membrane that sits over each muscle", "cell and electrically isolates the muscle cells from one another)"] }, { heading: "Lecture 6 recording 19: The Motor Neuron and the Neuromuscular Junction", id: "lecture-6-recording-19--the-motor-neuron-and-the-neuromuscul", items: ["•", "•", "Role of the Motorneuron:", "▪ An efferent neuron, also called a motor neuron, innervates the quadriceps muscle", "▪ Neurotransmitter is released at the synaptic terminals and results in muscle contraction", "▪ Motor unit → the motor neuron, its axon and all the muscle fibers it activates", "o The motor unit is the functional unit of the motor system and represents the", "smallest increment of force that can be generated in a muscle.", "▪ Each muscle fiber only has one synapse, called the neuromuscular junction", "o Comparison: In the nervous system there are 10,000 to 40,000 synaptic inputs", "onto any post-synaptic cell. In the case of the motor neuron innervating muscle,", "the postsynaptic cell is the muscle fiber, and each muscle fiber has only one", "synapse", "Neuromuscular Junction:", "▪ Neuromuscular junction (NMJ) → synapse between the efferent/motor neuron and the", "muscle fiber; do not directly make contact at the neuromuscular junction, but are", "separated by a small space, called the synaptic cleft or the synapse.", "o Muscle cell/muscle fiber is the postsynaptic cell", "▪ Directly-gated chemical synaptic transmission occurs at the NMJ", "▪ Motor end plate → region of the muscle fiber plasma membrane that lies directly under", "the terminal portion of the axon", "▪ An action potential travels down the efferent neuron to the presynaptic terminal", "resulting in depolarization and the opening of voltage-gated calcium channels", "▪", "•", "Calcium enters into the pre-synaptic terminal and causes the synaptic vesicles to fuse", "with the presynaptic membrane, releasing neurotransmitter into the synaptic cleft", "▪ Acetylcholine (ACH) is the neurotransmitter released by the efferent or motor neuron", "o An excitatory neurotransmitter", "▪ ACH binds to nicotinic receptors located on the postsynaptic membrane", "o Ionotropic receptors -receptors that form ion channels following the binding of", "a ligand; ligand-gated ion channels", "▪ Following the binding of ACH, the nicotinic receptors open and allow Na+ to enter the", "postsynaptic cell (the muscle cell)", "o Na+ moving into the cell causes a local depolarization", "o Muscle cells also have voltage-gated Na+ channels along the membrane close to", "the synaptic terminals.", "❖ The local depolarization will bring the muscle cell to threshold and open", "the voltage-gated Na+ channels, producing an action potential in the", "muscle", "Neuromuscular Junction:", "▪ Differences between synaptic transmission at NMJ and a central synapse:", "o One AP in motor neuron generates one AP in muscle cell (summation is required", "in the CNS)", "o Each muscle fiber (cell) is only innervated by one presynaptic axon", "o No inhibitory transmitters are released at NMJ (Acetylcholine = excitatory)"] }, { heading: "Lecture 6 recording 20: Events at the Neuromuscular Junction", id: "lecture-6-recording-20--events-at-the-neuromuscular-junction", items: ["•", "Role of the Motorneuron (9 slides):", "▪ Muscle cell = postsynaptic cell", "▪ One axon terminal/synaptic terminal synapses with one muscle cell/muscle fiber", "▪ Axon terminals contain vesicles filled with neurotransmitter (ACH)", "▪ At rest, muscle fiber is negatively inside with respect to extracellular space", "o Transverse tubule (T-tubule) is extracellular space and is positively charged with", "respect to the intracellular space", "▪ An action potential travels down to the presynaptic terminal, causing the release of ACH", "by exocytosis into the synaptic cleft", "▪ ACH binds to nicotinic receptors on the postsynaptic membrane, or the muscle cell, and", "Na+ enters into the cell", "o The muscle cell/fiber is depolarized in the region under the synaptic terminal", "(motor end plate) due to entry of Na+", "o Current flows between this region and the adjacent membrane, which is", "currently at rest, depolarizing the adjacent membrane to threshold and opening", "voltage-gated Na+ channels", "▪ An action potential is generated due to Na+ entry through the voltage-gated Na+", "channels", "▪ The action potential propagates or travels along the surface of the muscle fiber,", "travelling outward in both directions toward the ends of the muscle fiber and down the", "transverse tubules (T-tubules)"] }, { heading: "Lecture 6 recording 21: Excitation-contraction Coupling and Muscle Structure", id: "lecture-6-recording-21--excitation-contraction-coupling-and", items: ["•", "•", "•", "•", "Excitation-contraction Coupling:", "▪ Calcium:", "o Important for calcium release", "o Stored in the sarcoplasmic reticulum", "▪ How does an action potential travelling down the T-tubule result in the release of", "calcium needed for muscle contraction?", "o An action potential travels down the T- tubule and activates a voltage-gated Ca2+", "channel called the dihydropyridine or DHP receptor", "❖ Main role of the DHP receptor: act as a voltage sensor, responding to", "changes in the membrane potential", "❖ The DHP receptor is physically coupled to the ryanodine receptor", "through a foot process", "✓ Ryanodine receptor is a large molecule that includes the foot", "process and also forms a calcium channel which is inserted in", "the membrane of the sarcoplasmic reticulum", "✓ When the action potential travels down the T-tubule, it causes a", "conformational change in the DHP receptor. This", "conformational change acts through the foot process to open", "the ryanodine receptor channel located in the sarcoplasmic", "reticulum.", "✓ Calcium rushes out of the sarcoplasmic reticulum into the", "cytosol of the muscle cell through the ryanodine receptor", "✓ Calcium interacts with the contractile elements of the muscle", "cell underneath the sarcoplasmic reticulum", "Excitation-contraction Coupling: A Comparison", "▪ In the heart: the mechanism differs from that in skeletal muscle. There is no physical", "coupling in cardiac muscle but instead calcium-induced calcium release (more in", "cardiovascular section)", "Structure of a Muscle Cell:", "▪ Muscle cell/fiber:", "o Has myofibrils comprised of the contractile elements, or the myofilaments, actin", "and myosin.", "❖ Actin and myosin are protein filaments", "Structure of a Muscle Cell:", "▪ Sarcomere:", "o A structural unit of a myofibril in striated muscle", "o Bound on either side by Z-lines (interconnecting networks of proteins)", "o Contractile elements are the myofilaments, which include the thick filaments", "and the thin filaments", "o Thick filaments are made of the protein myosin", "o Thin filaments are made primarily of the protein actin", "❖ Thick filaments and thin filaments interact with each other and result in", "the actual shortening, or contraction, of the muscle", "•", "•", "Multiple Myofilaments:", "▪ Although the sarcomere shortens, the length of each myofilament does not change; the", "width of the H zone changes", "Sarcomere Contraction: An Animation:", "(This is an animation showing sarcomere shortening. Important point: During muscle", "contraction the sarcomere shortens and the H zone becomes narrower)"] }, { heading: "Lecture 7 recording 22: Molecular Participants in Skeletal Muscle Contraction", id: "lecture-7-recording-22--molecular-participants-in-skeletal-m", items: ["•", "•", "•", "•", "Molecular Participants:", "▪ Sliding Filament Theory: describes how a skeletal muscle contracts; involves 5 different", "molecules and calcium", "o Myosin → forms thick filaments", "o Actin → primary protein in thin filaments", "o Tropomyosin → regulatory protein binds to actin", "o Troponin → binds actin and tropomyosin, site of calcium binding", "o ATP → energy source to power muscle contraction", "o Calcium ions → released from the sarcoplasmic reticulum", "Myosin:", "▪ Myofibril are made of sarcomeres, which are composed of the myofilaments, the thick", "and thin filaments", "▪ Sarcomeres extend between two adjacent Z-lines", "▪ In skeletal muscle cells, the myosin molecules are bundled together to form the thick", "filaments", "o Myosin molecules have a long tail with 2 globular heads attached to the tails", "❖ The globular heads are called cross-bridges", "❖ The heads (cross-bridges) have the ability to move back and forth", "❖ The flexing movement of the head provides the “power stroke” for", "muscle contraction", "Myosin:", "▪ The cross-bridge has two binding sites", "o One site binds ATP and the other site binds actin.", "❖ The binding site for actin is on the top of the globular head and the", "binding site for ATP is at the base of the globular head", "▪ The myosin molecule can exist in two different states, a low energy state and a high", "energy state", "o In the low energy state the head of the myosin molecule is bent and myosin is", "bound to ATP", "o The myosin molecule switches between the low energy state to the high energy", "state by hydrolyzing a molecule of ATP", "o In the high energy state the head of myosin is bound to ADP and inorganic", "phosphate, and the position of the head has changed; the myosin head is now", "flat", "Thin Filament:", "▪", "▪", "•", "Actin is the major component of the thin filament and has a binding site for myosin", "2 other molecules are associated with the thin filaments are tropomyosin and troponin", "o Tropomyosin is a regulatory protein that is a double helical shaped strand which", "wraps itself around the actin filament and it covers up all of the myosin binding", "sites on the actin molecules", "❖ In the unstimulated muscle, the position of the tropomyosin covers the", "binding sites on the actin subunits, preventing myosin cross-bridges", "from interacting with or binding with actin", "Thin Filament:", "▪ Troponin is attached to the tropomyosin molecule at regular intervals", "o Troponin has a binding site for calcium", "o To expose the binding sites for myosin on actin, tropomyosin must be moved", "aside; this is facilitated by troponin", "❖ Calcium is released from the sarcoplasmic reticulum after an action", "potential and binds to its binding site on troponin. Troponin moves", "tropomyosin away from blocking the myosin binding sites on the actin", "molecule."] }, { heading: "Lecture 7 recording 23: Cross-bridge Cycling", id: "lecture-7-recording-23--cross-bridge-cycling", items: ["•", "Six Step of Cross-bridge Cycling:", "▪ Cross-bridge cycling is the cycle whereby myosin reaches up and grabs actin and causes", "the muscle to contract", "▪ Muscle action potential propagated through the T-tubule system, causing the release of", "calcium from the sarcoplasmic reticulum into the cytosol. Calcium is released due to", "coupling of the dihydropyridine receptor (the voltage-gated Ca2+ channel) with the", "ryanodine receptor.", "▪ Six steps of cross-bridge cycling:", "(We will go over theses in detail in this section. This slide is a quick summary of", "the steps)", "•", "Cross-bridge Cycling Overview:", "(We will look at the steps of cross-bridge cycling in more detail)", "•", "Cross-bridge Cycling", "▪ Step 1:", "o Exposure of the binding sites on the actin molecule. An action potential causes", "the release of calcium from the sarcoplasmic reticulum. Calcium floods into the", "cytosol of the muscle fiber. Calcium binds to troponin molecules on the thin", "filament and causes a conformational change in the troponin-tropomyosin", "complex, causing the tropomyosin to be dragged away from the myosin binding", "sites on actin, exposing the myosin binding sites on actin.", "o Myosin must be in its high energy state to bind to its binding site on actin. In the", "high energy state, ATP has been hydrolyzed into adenosine diphosphate, or", "ADP, and inorganic phosphate; the energy from the hydrolysis of ATP puts the", "myosin head into its high energy state, a condition that prepares it for binding", "to actin.", "▪", "▪", "▪", "▪", "▪", "▪", "Step 2:", "o The myosin molecule binds to the myosin binding site on actin. The myosin", "cross-bridge is energized, or in its high energy state.", "Step 3:", "o The power stroke. The myosin head, which is bound to its binding site on actin,", "pivots forward. This pivoting of the head causes the H-zone to shorten, pushing", "the actin molecule to the middle of the sarcomere. In addition, during the", "power stroke the binding of myosin to actin causes a conformational change in", "the cross-bridge, which results in the release of ADP and inorganic phosphate", "from their binding site on the head of the myosin molecule.", "Step 4:", "o The myosin molecule, which is in its low energy state and bent forward, is", "released from the thin filament.", "❖ In order for the myosin head to be released from the thin filament, a", "molecule of ATP must bind to its binding site at the base of the myosin", "head; this causes a conformational change, releasing the myosin head", "from its binding site on actin.", "Step 5:", "o Re-energizing and repositioning of the cross-bridges.", "❖ The myosin head is reset, ready to start a new cycle and generate more", "muscle contractions. ATP has bound to its binding site on the myosin", "head causing the release of the myosin cross-bridge from actin. The", "release of the myosin cross-bridge from actin triggers the hydrolysis of", "ATP into adenosine diphosphate and inorganic phosphate. Energy is", "transferred from ATP to the myosin cross-bridge. The myosin head is", "tilted up, back into its high energy state where it is bound to adenosine", "diphosphate and inorganic phosphate, ready to bind to actin again.", "o ATP is very important for muscle contraction:", "❖ The binding of ATP is essential for the release of the myosin cross-bridge", "from its binding site on actin.", "❖ The hydrolysis of ATP is essential for re-energizing and re-positioning", "the myosin molecule from its low energy state to its high energy state,", "to begin another cross-bridge cycle.", "Step 6:", "o Removal of calcium ions. The calcium ions that are bound to troponin are", "released and would move back into the sarcoplasmic reticulum by the action of", "ion pumps.", "o When the calcium ions are released from troponin, the troponin/tropomyosin", "complex again covers the binding sites on actin", "At the neuromuscular junction, there is no inhibitory neurotransmitter; only", "acetylcholine is released and it is always excitatory. How then does muscle contraction", "stop or why do muscles ever stop contracting?", "o The reason for this is because of the absence of calcium ions"] }, { heading: "Lecture 7 recording 24: More on the Cross-bridge Cycle", id: "lecture-7-recording-24--more-on-the-cross-bridge-cycle", items: ["•", "•", "•", "Multiple Cross-bridge Cycles:", "▪ At any given time, there are a large number of myosin molecules that are in the high", "energy state and ready to bind to actin. Depending on the task that you are doing, and", "depending on the amount of ATP that is present in your body, the number of myosin", "molecules that are ready to participate in contraction can be varied.", "o This will vary the intensity of the muscle contraction and also the duration of", "the muscle contraction", "❖ The more ATP present, the more myosin molecules are energized and as", "a result, the longer the duration and the larger the amplitude of the", "muscle contractions", "❖ The less ATP is present, the less myosin molecules that are in the high", "energy state and as a result, the shorter the duration and the smaller", "the amplitude of the muscle contractions", "▪ During a contraction, all cross-bridges are neither bound nor disconnected at the same", "time", "Calcium Pumps:", "▪ Calcium must move back into the sarcoplasmic reticulum from the cytosol after muscle", "contraction is completed", "o Calcium is taken back up into the sarcoplasmic reticulum via an active transport", "pump present in the membrane of the sarcoplasmic reticulum", "❖ This active transport pump requires ATP for activity", "Role of ATP:", "▪ In the muscle cell the energy molecule ATP plays an important role in:", "o Energizing the power stroke of the myosin cross-bridge", "o Disconnecting the myosin cross-bridge from the binding site on actin at the", "conclusion of a power stroke", "o Pumping Ca2+ back into the sarcoplasmic reticulum"] }, { heading: "Lecture 7 recording 25: Types of Skeletal Muscle Fibers", id: "lecture-7-recording-25--types-of-skeletal-muscle-fibers", items: ["•", "•", "Metabolic Variations of Muscle Fiber Types:", "▪ Two main types of muscle cells/muscle fibers: white muscle fibers and red muscle fibers", "o Differ in size and coloration", "o Differ in mechanisms for synthesizing ATP", "4 slides: Features of White Muscle Fibers, Features of Red Muscle Fibers, Metabolism in White", "Muscle Fibers and Metabolism in Red Muscle Fibers", "▪ Helpful things to know:", "o Myoglobin – the primary oxygen-carrying protein of muscle tissues", "o Capillaries – bring oxygen to the muscle cells", "o Mitochondria – require oxygen brought by blood capillaries to make ATP", "o Glycogen – the storage form of glucose; broken down to release glucose", "o Glycolysis – uses glucose to make ATP in the absence of oxygen (anaerobic)", "This table summarizes the information in the 4 slides (Features of White Muscle Fibers, Features of Red", "Muscle Fibers, Metabolism in White Muscle Fibers and Metabolism in Red Muscle Fibers)", "Characteristic", "Also called:", "Used for:", "Size:", "Myoglobin:", "Blood supply:", "Mitochondria:", "Glycogen Content:", "Process used to make ATP:", "Speed of cross-bridge cycling", "Fatigue", "•", "Red Muscle Fibers", "Slow-twitch fibers", "Long-lasting continuous", "contractions", "Half the diameter of white", "muscle fibers", "Large quantity of myoglobin", "High blood supply (many", "capillaries)", "Numerous mitochondria", "Low glycogen content (do not", "rely solely on glucose to make", "ATP but use aerobic processes)", "Krebs cycle and oxidative", "phosphorylation (aerobic", "processes - require oxygen)", "Cross-bridge cycling occurs", "relatively slowly", "Fatigue resistance and high", "endurance", "White Muscle Fibers", "Fast-twitch fibers", "Intense but short-lasting", "contractions", "Large diameter", "Reduced myoglobin", "Poor blood supply (few", "capillaries)", "Few mitochondria", "High glycogen content", "(glycogen=storage form of", "glucose)", "Glycolysis (anaerobic process does not require oxygen)", "Rapid cross-bridge cycling", "results in fast contractions", "Fatigue rapidly due to build-up", "of lactic acid and glycogen", "Muscle Fiber Types:", "(This slide shows the proportion of red and white muscle fiber types in different people. You", "do not need to memorize this – it is simply for interest only)", "•", "The Stretch Reflex:", "(This slide summarizes the stretch reflex and what we have learned about the neurons and", "the muscles involved)"] }, ], }; Object.assign(window, { SOURCE_SLIDES, SOURCE_NOTES, LECTURE_VIDEOS });