Electrical Activity Of The Heart PDF

BIOL2220 –Systems Physiology Electrical Activity of the Heart BIOL2220 –Systems Physiology Lecture 2: Homeostasis BIOL2220 Systems Physiology COMPLEX SYSTEMS Homeostasis A CENTRAL ORGANISING PRINCIPLE OF PHYSIOLOGY Lecture 2: Homeostasis LEARNING OBJECTIVES On successful c...

BIOL2220 –Systems Physiology Electrical Activity of the Heart BIOL2220 –Systems Physiology Lecture 2: Homeostasis BIOL2220 Systems Physiology COMPLEX SYSTEMS Homeostasis A CENTRAL ORGANISING PRINCIPLE OF PHYSIOLOGY Lecture 2: Homeostasis LEARNING OBJECTIVES On successful completion of this lecture, you will be able to: Define homeostasis Explain the significance of homeostasis to the function of the body Describe the role of positive and negative feedback loops 4 Lecture 2: Homeostasis LEARNING OBJECTIVES On successful completion of this lecture, you will be able to: Define homeostasis Explain the significance of homeostasis to the function of the body Describe the role of positive and negative feedback loops 5 Homeostasis A CENTRAL ORGANISING PRINCIPLE OF PHYSIOLOGY Homeostasis A CENTRAL ORGANISING PRINCIPLE OF PHYSIOLOGY The maintenance of relatively constant conditions in the internal environment is known as homeostasis In fact, nine of the ten organ systems function to maintain homeostasis Disruption of homeostasis can lead to disease, yet the body is also capable of adapting to mild stressors that disrupts homeostasis Regulated variables need to remain constant under normal conditions Composition Temperature Volume Homeostasis A CENTRAL ORGANISING PRINCIPLE OF PHYSIOLOGY Homeostasis A CENTRAL ORGANISING PRINCIPLE OF PHYSIOLOGY Lecture 2: Homeostasis LEARNING OBJECTIVES On successful completion of this lecture, you will be able to: Define homeostasis Explain the significance of homeostasis to the function of the body Describe the role of positive and negative feedback loops 10 Homeostasis FEEDBACK LOOPS Any deviation of a regulated variable away from its normal (set) value stimulates responses which seek to reduce deviation Negative feedback Positive feedback loops Homeostasis FEEDBACK LOOPS Any deviation of a regulated variable away from its normal (set) value stimulates responses which seek to reduce deviation Negative feedback Homeostasis NEGATIVE FEEDBACK LOOPS Any deviation of a regulated variable away from its normal (set) value stimulates responses which seek to reduce deviation Negative feedback Homeostasis POSITIVE FEEDBACK LOOPS A few positive feed-back systems are important in physiology The response of the system goes in the same direction as the change that sets it in motion https://www.youtube.com/watch?v=bfuOljRU1nk&t=290s BIOL2220 –Systems Physiology Lecture 3: Cell Communication Cell Communication CELL SIGNALLING Cell Communication CELL SIGNALLING Direct Gap junctions Indirect Nervous System Endocrine System wired connections wireless connections Lecture 3: Cell Communication LEARNING OBJECTIVES On successful completion of this lecture, you will be able to: Describe the different types of cellular signalling and the processes involved in them Explain the primary mechanisms that cells use to communicate to regulate tissue function Describe the role of hormones as signals in the human body Understand the concept of endocrine axes and the negative feedback in maintaining homeostasis 4 Lecture 3: Cell Communication LEARNING OBJECTIVES On successful completion of this lecture, you will be able to: Describe the different types of cellular signalling and the processes involved in them Explain the primary mechanisms that cells use to communicate to regulate tissue function Describe the role of hormones as signals in the human body Understand the concept of endocrine axes and the negative feedback in maintaining homeostasis 5 Cell Signalling and Hormones CELL COMMUNICATION Specialised cells combine to form tissues and tissues to form organs with complex functions Communication between multiple specialised cells is needed to allow tissues and organs to perform their function and maintain homeostasis Cells communicate by sending and receiving chemical signals (transmitters) To detect and respond to cues in their environment For example: signalling molecules relay positional information during development Involves gap junctions and cell-to-cell interactions FMHS | Macquarie MD Cell Communication RECEPTORS Cells communicate by sending and receiving chemical signals (transmitters) Neurotransmitters Growth factors Metabolites Hormones Extracellular matrix components Ions Cells use receptors that bind these signalling molecules and initiate a physiological response. Receptors can be either on the cell surface or inside the cell Receptors transmit the signal through a sequence of molecular switches to Image: Different types of cell communication signalling pathways. Image modified from "Signaling molecules and cellular receptors: Figure 1," by OpenStax College, Biology (CC BY 3.0). FMHS | Macquarie MD Cell Communication TYPES OF CELLULAR COMMUNICATION Cells communicate by sending and receiving chemical signals (transmitters) Juxtracrine Direct contact between cells Gap junctions Paracrine Short distance, immediate cellular environment Local coordination (proliferation and differentiation) Autocrine Cell signals to self Self-stimulation (immune system) or self-identity (development) Image: Different types of cell communication Endocrine Image modified from "Signaling molecules and cellular receptors: Figure 1," by OpenStax College, Biology (CC BY 3.0). To distant sites, via hormones in the blood stream Development and physiology FMHS | Macquarie MD  Cell Communication SPECIALISED JUNCTIONS Gap junctions are formed when two connexons (comprised of connexin proteins) on adjacent cells come together to form a narrow pore between the cells. This allows small molecules and ions to move from one cell to another providing metabolic and electrical coupling between cells. Example: cardiac tissue has extensive gap junctions, and the rapid movement of ions through these junctions helps the Image: Gap junctions are clusters of channels that form tunnels of aqueous connectivity between cells. tissue beat in rhythm. © 2010 Nature Education All rights reserved. FMHS | Macquarie MD Cell Communication TYPES OF CELLULAR COMMUNICATION Cells communicate by sending and receiving chemical signals (transmitters) Juxtracrine Direct contact between cells Gap junctions Paracrine Short distance, immediate cellular environment Local coordination (proliferation and differentiation) Autocrine Cell signals to self Self-stimulation (immune system) or self-identity (development) Endocrine Image: Different types of cell communication Image modified from "Signaling molecules and cellular receptors: To distant sites, via hormones in the blood stream Figure 1," by OpenStax College, Biology (CC BY 3.0). Development and physiology FMHS | Macquarie MD  DR LUCINDA MCROBB FMHS | Macquarie MD  DR LUCINDA MCROBB FMHS | Macquarie MD  DR LUCINDA MCROBB FMHS | Macquarie MD Lecture 3: Cell Communication LEARNING OBJECTIVES On successful completion of this lecture, you will be able to: Describe the different types of cellular signalling and the processes involved in them Explain the primary mechanisms that cells use to communicate to regulate tissue function Describe the role of hormones as signals in the human body Understand the concept of endocrine axes and the negative feedback in maintaining homeostasis 14 Endocrine signalling CLASSICAL DEFINITION OF A HORMONE Hormones (signals/ligands) Produced in specialised cells/organs, travel via the blood to distal targets Endocrine glands (transmitters) Have specialised cells that produce hormones and release into blood Target organs/tissues (reception) Target cells must have specific receptors Circulating hormones will contact all cells via the blood – but only some will respond to these signals 9 DR LUCINDA MCROBB  Hormones as signals HORMONES ARE CLASSIFIED ACCORDING TO BIOCHEMISTRY Classical hormones classified according to their basic biochemistry Solubility (polar/non-polar) affects many characteristics (production/transport/receptors) Steroid Peptide-Protein hormones Amine hormones hormones Derived from the Long chains of amino acids, or Modified amino lipid cholesterol Short chains of linked amino acids acids Peptide Eg oxytocin Protein Eg Growth hormone Eg testosterone Eg norepinephrine Anatomy & Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/, Jun 19, 2013. 13 DR LUCINDA MCROBB  Biochemistry and hormone actions The biochemical differences in these hormone classes determines how each group of hormones are: Synthesised and released (stored in vesicles or released as synthesised) Transported in the blood (protein bound or unbound) Received at the cell (intracellular, extracellular) Elicit cell actions and responses (rapid, slow, sustained, cyclical, pulsatile) 14 DR LUCINDA MCROBB Steroid hormones – cell reception and signal transduction Classical genomic signalling Non-genomic signalling Lipophilic nature means they can In recent years, extracellular diffuse across the plasma receptors (GPCRs) for steroid membrane and interact with hormones have been identified– receptors inside the cell although exact contributions not as well understood DR LUCINDA MCROBB Peptide hormones – cell reception and signal transduction CELL RECEPTION As they are soluble (hydrophilic) they cannot cross the plasma membrane Must interact with extracellular receptors at cell surface Use of intracellular signalling cascades (kinase, second messengers) Rapid mechanism of signalling, amplification of very small signal in blood Hormones THREE MAJOR CLASSES OF RECEPTORS G-protein-coupled receptors, ion channel receptors, G-protein-coupled receptors and enzyme-linked receptors Membrane receptors interact with both extracellular signals and molecules within the cell. This permits signalling molecules to affect cell function without actually entering the cell. Ion channel receptors acetylcholine receptor Image: Examples of two classes of receptors © 2010 Nature Education All rights reserved. FMHS | Macquarie MD Receptors can be ligand-gated channels Eg post-synaptic ionotropic glutamate receptors (note this is not a mechanism per se for classical hormone receptors) 21 Enzyme linked receptors; direct activation of protein kinases Insulin Prolactin 22  G-proteins and signal transduction G protein; signal tranduction cAMP; second messenger system With no hormone on the receptor, guanosine diphosphate (GDP) is bound to the α subunit of the G protein When hormone attaches to the receptor the “regulatory” components (β & γ) detach from the α subunit and the GDP bound to the α subunit is exchanged for GPT This activated α subunit alters the function of another membrane protein usually a channel or an enzyme (adenylate cyclase, phospholipase C) 23  Multiple steps from hormone binding to effects in the cell allows for the control of many functions and amplification of the signal As well as amplification, each hormone can produce many different functions in the one cell and in different cells 24 Peptide-like amine hormones Hormones CHEMICAL CLASSIFICATION FMHS | Macquarie MD Lecture 3: Cell Communication LEARNING OBJECTIVES On successful completion of this lecture, you will be able to: Describe the different types of cellular signalling and the processes involved in them Explain the primary mechanisms that cells use to communicate to regulate tissue function Describe the role of hormones as signals in the human body Understand the concept of endocrine axes and the negative feedback in maintaining homeostasis 27  Endocrinology ENDOCRINE ORGANS Primary endocrine organs include the pituitary gland (which is divided into anterior and posterior lobes), pineal gland, thyroid gland, parathyroid glands, thymus, pancreas, and gonads. Secretion by the anterior pituitary is regulated by tropic hormones secreted by neurosecretory cells in the hypothalamus. Secretion of these and other hormones is regulated by negative feedback. A secondary endocrine organ secretes a hormone in addition to carrying out another primary function. Secondary endocrine organs include the heart, liver, and kidneys. FMHS | Macquarie MD Primary endocrine organs Endocrine Hormone examples gland/tissue Hypothalamus TRH, CRH, GHRH, GnRH, dopamine (PIH), somatostatin (GHIH) Pituitary Gland Anterior - GH, TSH, ACTH, FSH, MSH, LH, Prolactin Posterior - oxytocin, vasopressin/ADH Pineal Gland Melatonin Thyroid and T3, T4, Calcitonin, parathyroid PTH Adrenal glands Mineralocorticoids, glucocorticoids, sex (cortex and hormones (androgens, estrogens) medulla) corticosteroids or catecholamines (adrenaline, noradrenaline, dopamine) Pancreas Insulin, glucagon, somatostatin Ovary Estrogens, progesterone Testes Androgens, estradiol Placenta hCG Classical endocrine organs 10 DR LUCINDA MCROBB Secondary endocrine functions Other organs have secondary endocrine functions (ie their primary function is not hormone production) Endocrine Hormone examples gland/tissue Kidney Calcitriol, renin, erythropoietin Uterus Prolactin, relaxin Liver Insulin-like growth factor (IGF-1), Thrombopoietin (THPO) Stomach Gastrin, ghrelin, histamine, somatostatin, neuropeptide Y Small intestine Cholecystokinin, secretin, somatostatin Thymus Thymopoietin Heart Atrial natriuretic peptide 11 DR LUCINDA MCROBB  Endocrinology ENDOCRINE HORMONES A trophic hormone is a hormone that controls the secretion of other hormones Hypothalamus, anterior pituitary (thyroid) A stimulating hormone increases the secretion of another hormone An inhibiting hormone decreases the secretion of another hormone The hypothalamus releases a tropic hormone that effects the release of another tropic hormone from the anterior pituitary; this tropic hormone FMHS | Macquarie MD  Endocrinology ENDOCRINE AXES The hypothalamus releases a tropic hormone that effects the release of another tropic hormone from the anterior pituitary This tropic hormone then effects the release of a third hormone from another endocrine gland, and this third hormone exerts effects on target cells through-out the body. FMHS | Macquarie MD  Endocrinology ENDOCRINE AXES FMHS | Macquarie MD  Hypothalamus-pituitary-thyroid axis (HPT axis) Silverthorn, Human Physiology 6th ed 34  Negative feedback loop for cortisol via the hypothalamic-pituitary- adrenal (HPA) pathway paraventricular nucleus (PVN) CRH; corticotrophin releasing hormone Portal hyophyseal blood vessels ACTH; adrenocorticotrophic hormone Silverthorn, Human Physiology 6th ed 35 Lecture 1 Nervous System Overview KEVIN DANASTAS BIOL2230 Neurophysiology Readings Stanfield (2017) Principles of Human Physiology. 6th Edition. Pearson. ▪ Chapter 7: 7.1 – 7.2 2 Learning objectives LO1: Describe the different functional types of neurons in the CNS LO2: Describe the different functional types of glial cells in the CNS and PNS LO3: Describe the structural organisation of neurons in the nervous system 3 Vertebrate Nervous System CNS: Brain, cranial nerve (CN) II (optic nerve), spinal cord PNS: CN I, III – XII, spinal nerves (31), peripheral nerves & neuromuscular junctions 4  Composition of the Nervous System Neural tissue is comprised of two main cell types: ▪ Neurons ▪ Neuroglia (or simply ‘glia’) – non-neuronal cells that support neuronal function Neurons are made up of: ▪ Cell body (soma) – contains dendrites nucleus, mitochondria, endoplasmic reticulum, Golgi apparatus etc. cell body ▪ Dendrites – receive information (soma) from other neurons or cells ▪ Axon – sends information to another destination axon Copyright © 2011 Pearson Education, Inc., publishing as Benjamin Cummings. 5 http://oerpub.github.io/epubjs-demo-book/content/m46509.xhtml  What are neurons? Excitable cells – electrically active cells that can (rapidly) alter the voltage across their cell membrane in order to: ▪ transduce and transfer information ▪ communicate with other cells ▪ bring about physiological changes in the body https://www.geekwire.com/2016/scientists-trace-the-myriad-connections-in-a-tiny-tangle-of-mouse-neurons/ https://fellerlab.squarespace.com/research/ 6 What are neurons? Highly diverse, but fall into 3 broad functional categories: Sensory (afferent) neurons and receptors ▪ detect and transduce stimuli arising from outside (e.g. light, sound) or inside (e.g. blood pressure, muscle stretch) the body and transmit the resulting (afferent) neural signals to the CNS for processing Motor (efferent) neurons ▪ carry efferent signals from the CNS to effector organs to bring about a change, e.g. contraction of muscle tissue, release of substances from a gland Interneurons ▪ connect neurons to one another in the CNS, allow the CNS to communicate with sensory and motor neurons, form circuits for processing neural information 7  Types of neurons Huge morphological and physiological diversity Reflects functional differences Copyright © 2011 Pearson Education, Inc., publishing as Benjamin Cummings. 8  Neuronal communication Neurons communicate with each other through synapses Copyright © 2011 Pearson Education, Inc., publishing as 9 Benjamin Cummings.  Neuronal communication Axons range in length from 1 millimetre (eg. interneurons in the brain) to 1 meter (eg. sciatic nerve) Nucleus and most organelles are located in the cell body, but proteins (eg. neurotransmitters) need to be transported to the axon termini Neurons have specialised axonal transport mechanisms ▪ Anterograde transport: from the cell body to the axon termini ▪ Retrograde transport: from the axon termini to the cell body Axons are (mostly) made up of microtubules, which act as ‘train tracks’ to transport cargo up and down the axon Copyright © 2011 Pearson Education, Inc., publishing as 10 Benjamin Cummings. Learning objectives LO1: Describe the different functional types of neurons in the CNS LO2: Describe the different functional types of glial cells in the CNS and PNS LO3: Describe the structural organisation of neurons in the nervous system 11 Neuroglia (‘glia’) Non-neuronal cells that are critical to the function of neurons Main functions: 1. Physical support for neurons 2. Supply nutrients and oxygen to neurons 3. Electrical insulation of neurons 4. Destroy pathogens and remove dead neurons 5. Information processing & more… Main types: 1. Astrocytes 2. Oligodendrocytes & Schwann cells 3. Microglia 4. Ependymal cells 12  Astrocytes (CNS) Transport nutrients (e.g. glucose) from blood vessels to neurons Remove neurotransmitters (glutamate and GABA) released by neurons during synaptic transmission Regulate extracellular potassium concentrations Guide developing neurons, and their axons to influence synaptic connectivity Synthesise and store important molecules that are used by neurons https://labs.mcdb.ucsb.edu/fisher/steven/images.html 13  Oligodendrocytes (CNS) and Schwann cells (PNS) Generate the myelin sheaths that surrounds the axons of many neurons. Myelin is: ▪ a greatly extended and modified portion of the cell membrane that wraps around the axon in a spiral fashion ▪ rich in lipid → provides effective electrical insulation of the axon Copyright © 2011 Pearson Education, Inc., publishing as Benjamin Cummings. 14  Microglia (CNS) Immune effector cells of the CNS Phagocytose cell debris following injury or pathogens in the case of infection Brain development and homeostasis Promote regrowth and remapping of damaged neural circuitry Involved in neuronal and synaptic plasticity Salter and Stevens (2017) Microglia emerge as central players in brain disease. Nature Medicine 23: 1018-1027 DOI: 10.1038/nm.4397 15  Ependymal cells (CNS) Line ventricles (fluid-filled cavities) in the brain and the central canal of spinal cord Assist in production of cerebrospinal fluid (CSF) CSF cushions and supplies nutrients to the brain Microvilli beat in a coordinated fashion to circulate CSF Copyright © The McGraw-Hill Companies, Inc. 16  Glial cells in the nervous system Copyright © The McGraw-Hill Companies, Inc. 17 Learning objectives LO1: Describe the different functional types of neurons in the CNS LO2: Describe the different functional types of glial cells in the CNS and PNS LO3: Describe the structural organisation of neurons in the nervous system 18 Structural organisation of the CNS Grey (gray) matter ▪ Cell bodies and dendrites of CNS neurons and some glia ▪ Greyish-pink colour due to Nissl bodies (rough ER; organelles of protein synthesis) in cells and blood in the capillaries ▪ Location of synaptic connections between neurons White matter ▪ Axons of CNS neurons ▪ Myelin sheath (oligodendrocytes) gives white appearance due to high lipid content 19  Neurons are commonly organised in two ways: Brain: outer grey matter, inner white matter Spinal cord: inner grey matter, outer white matter Grey matter (cerebral cortex) White matter Grey matter Grey matter White matter (subcortical) 20 L: Stanfield (2014) Principles of Human Physiology; 5th Edition. Pearson  Neurons are commonly organised in two ways: Layers (laminae) Compact clusters of neuronal cell bodies: ▪ ‘Nuclei’ in the CNS ▪ ‘Ganglia’ in the PNS Grey matter (cerebral cortex) Ganglia White matter Grey matter Grey matter White matter (subcortical) 21 L: Stanfield (2014) Principles of Human Physiology; 5th Edition. Pearson R: Copyright (c) The McGraw-Hill Companies, Inc. Neural circuits Neurons do not function in isolation – they are organised into circuits Circuits vary widely in complexity, connectivity and function A ‘simple’ circuit such as the myotactic or ‘knee-jerk’ spinal reflex loop involves relatively little neuronal processing: 22  Neural circuits An example of a more complex circuit in the brain, one that governs our perception and interpretation of painful stimuli – the so called ‘pain matrix’ Comprises multiple brain areas which also have many other (non-pain) functions Includes areas responsible for immediate the physical response (pain detection, discrimination and avoidance) as well as pain-related mood and emotion (anger, depression, anxiety, stress) Monroe et al. (2015) Sex differences in psychophysical and neurophysiological responses to pain in older adults: a cross-sectional study. Biol. Sex Diff. 6: 25. DOI: 10.1186/s13293-015- 23 0041-y Lecture 3 Resting Membrane Potential KEVIN DANASTAS BIOL2230 Neurophysiology Readings Stanfield (2017) Principles of Human Physiology. 6th Edition. Pearson. ▪ Chapters 4 – especially 4.1 and 4.2 (very important!) ▪ Chapter 7 – especially 7.1 – 7.3 2 Learning objectives LO1: Explain how the selective permeability of the cell membrane and related differences in ionic composition of the ECF and ICF give rise to electrochemical gradients across the membrane LO2: Explain the role of ion channels, leak channels and ion pumps and how they help maintain chemical gradients across the membrane LO3: Describe the principals of equimolality and electrical neutrality and the effects this has on ionic gradients LO4: Understand how the Nernst equation can be used to calculate the equilibrium potential for a given ion and thus predict how that ion will behave when the membrane potential changes LO5: Understand how the relative permeability of the membrane to different ions gives rise to, and influences, the resting membrane potential 3  Body fluid compartments Conceptually, body fluid can be divided into 2 compartments separated by the cell membrane: Solids ▪ Intracellular fluid (ICF) = cytosol ♂ 40% ▪ Extracellular fluid (ECF) ♀ 45% Plasma (7.5%) 45% Functional Extracellular Interstitial fluid (20% ) ECF Fluid (ECF) 2:1 ratio Fluids Bone/dense CT; transcellular fluid1 (17.5%) 42 litres ♂ 60% ♀ 55% 55% Intracellular ICF Fluid (ICF) 1 CT – connective tissue; transcellular fluids include: saliva, CSF, gastro-intestinal fluids, synovial fluid, bladder urine, aqueous humour, etc. 4  Typical composition of ICF and ECF Intracellular (mM) Extracellular (mM) Potassium (K+) 140.0 4.0 Sodium (Na+) 15.0 145.0 Chloride (Cl-) 4.0 115.0 Magnesium (Mg2+) 0.8 1.5 Calcium (Ca2+)