Paramedicine – Medical Physiology I Lecture 4 F2024 PDF

PAR3623 Paramedicine – Medical Physiology I F2024 Lecture 4 Bioelectricity I and Cells of the Nervous System  Copyright / Intellectual Property Notice Materials posted to courses are subject to Intellectual Property and Copyright protection, and as such...

PAR3623 Paramedicine – Medical Physiology I F2024 Lecture 4 Bioelectricity I and Cells of the Nervous System  Copyright / Intellectual Property Notice Materials posted to courses are subject to Intellectual Property and Copyright protection, and as such cannot be used and posted for public dissemination without prior permission from the College. For clarity, these protections are automatic once a work is created, and applies whether or not a copyright statement appears on the material. Students are bound by College policies, including AA 34 - Copyright, and SA 07 - Student Code of Conduct, and any student found to be using or posting course materials for public dissemination without permission is in breach of these policies and may be sanctioned.  Channel structure and polarity Concept of the concentration gradient Active transport - recap ATPase Form of a cell vs. its function Cell types – recap There were a few others but if you’re stuck or worried, please see me! Dr. Pasan Fernando  Concentration Gradient Create a pictorial that illustrates the concept of a concentration gradient. The pictorial does not have to related to cell biology or the membrane. The most interesting ones are those that exemplify everyday life. § See the video on concentration gradients in BS Dr. Pasan Fernando 4  Aquaporin – Atomic structure § The atomic structure of aquaporin (AQP1) § Three features give specificity for water through AQP1 § Size restriction Ø 8 to 2.8 angstrom variance § Electrostatic forces Ø AA residue Argenine 195 creates a barrier to cations including H3O+ § Water dipole Ø Shape at the midpoint of the channel causes water molecules to reorient – gives further size and charge specificity Dr. Pasan Fernando Kozono et al. J Clin Invest 2002 109(11): 1395-1399 5  Active Transport What is the difference between passive and active transport Identify the two main types of active transport Dr. Pasan Fernando 6  § ATPases – family of enzymes § Can form or break ATP to help ions move (transport) across membranes Dr. Pasan Fernando 7  Cell Form vs. Cell Function Dr. Pasan Fernando 8  Overview Of Major Cell Types In Body § 35 trillion cells Skeletal muscle cell § >200 cell types Smooth muscle cells Cardiac muscle cells § Four major classes: Ø Neurons Muscle cells Blood cells Ø Muscle cells Basement Ø Epithelial cells membrane Bone cells Basement Ø Connective cells Lumen membrane Dr. Pasan Fernando Basement membrane Fibroblasts Epithelial cells (in skin and other tissues) Connective tissue cells 9  Cell Junctions Some cells are “free” (not bound to any other cells) § Examples: blood cells, sperm cells Most cells are bound together to form tissues and organs Three ways (for us to consider) that cells can be bound to each other § Tight junctions § Desmosomes § Gap junctions Dr. Pasan Fernando § Hemidesmosomes § Adherens junctions  Cellular Responses to Stress Objectives: ü Describe the cellular responses to stress ü Identify the differences between apoptosis and necrosis ü Relate the concepts of cellular stress in normal tissue function Dr. Pasan Fernando 11  Cellular Response to Stress - Adaptation § A normal cell has a narrow range of function § Physiologic adaptations can be metabolic or structural but are reversible. § Adaptative response: hypertrophy and elevated function, hyperplasia, atrophy, metaplasia Dr. Pasan Fernando  Cellular Response to Stress - Injury § Injury results when the cells are not able to adapt § Stimulus or stress pushes the cell to operate outside of its normal range § Stimulus persists, causing changes to critical cellular components needed for cell function. § Changes in the cell occur in progressive stages Dr. Pasan Fernando 13  Cell Death § Cells are constantly under stress; causing homeostatic imbalance § If a cell cannot recover quickly from a stressful insult, it will eliminate itself – programmed cell death § An overwhelming insult will cause the cell to rupture and undergo uncontrolled cell death – necrosis Ø Most trauma incidents will invoke cellular necrosis Ø A common response to necrosis is inflammation § Cells in the stomach and small intestine – constantly die and new cells are made § Cells in the heart (myocytes) do not readily die but if so, they do not easily renew Dr. Pasan Fernando Ø Renewal in the heart is limited – implications for heart disease 14  Apoptosis § Proteins are continually cycled throughout the lifespan of a cell § Proteins can be marked for degradation § When a cell can no longer maintain homeostasis, its proteins become marked to trigger a cell death response § Controlled elimination of a cell is called programmed cell death or apoptosis § In some instances, the cell does not have time or is unable to 'quietly' kill itself § It undergoes an uncontrolled death response (lysis, cell disruption, cell damage Ø Called cellular necrosis Dr. Pasan Fernando 15  Apoptosis vs. Necrosis Apoptosis Necrosis membrane blebbing, but still intact membrane integrity lost shrinkage: chromatin aggregate, swelling: cytoplasm and mitochondria cytoplasm shrinks, nucleus condenses, leaky mitochondria cells fragment into smaller bodies cells undergo lysis (apoptotic bodies) Dr. Pasan Fernando  Apoptosis vs. Necrosis Apoptosis Necrosis energy dependent passive process, no energy required regulated DNA fragmentation-laddering random DNA digestion-smearing specific enzyme cascades are activated nonspecific, uncoordinated enzymatic activation affects individual cells affects groups/sheets of cells induced by physiological stimuli (growth non-physiological stimuli factors, hormones, cellular environment) (lytic viruses, hypoxia, ischemia) Dr. Pasan Fernando no inflammatory response inflammatory response  Stress and Tissue Function - Example Asthma induced allergic reaction § Chronic allergic responses cause long term remodeling of the airways Stenosis of the trachea or bronchioles is common - lumen narrows § Which of the following cellular adaptive responses are occurring? Explain Ø hypertrophy, elevated function, hyperplasia, metaplasia, atrophy Dr. Pasan Fernando 18  Lecture 4 Review the concentration gradient and now consider the influence of charge – electrical gradients Principles of bioelectricity – what do we need to know before we begin? Electrochemical gradients Overview of the nervous system Dr. Pasan Fernando Overview of the cells of the nervous system 19  Selective permeability Permeability § Ability to cross the membrane Impermeable § Not able to cross the membrane Plasma membrane § Selectively permeable Ø Some things can cross while others cannot Dr. Pasan Fernando  Selective permeability Dr. Pasan Fernando  Gradients across the plasma membrane Objective: § Distinguish between a concentration gradient and an electrical gradient. Dr. Pasan Fernando  Concentration gradient § Difference in the concentration of a chemical from one place to another, such as from the inside to the outside of the plasma membrane. Dr. Pasan Fernando  Electrical gradient § Every cell has a distribution of positive and negative charges along its membrane § A difference in electrical charges between two regions, such as across the plasma membrane is the electrical gradient § Some cells can use the electrical gradient to function (neurons, all muscle cells) – excitable cells § Other cells do not use the electrical gradient; they just maintain the gradient (epithelial cell, erythrocyte, Dr. Pasan Fernando hepatocyte, renal, splanchnic, etc.)  Principles of Bioelectricity Some basic concepts to set the stage: Extracellular fluid § Collection of charges on either side of the Cl- membrane (ECF/ICF) Na+ § Opposite charges are attracted to each other Plasma membrane § Energy is needed to keep opposite charges separated across a membrane K+ § Energy is liberated when charges move toward Cytosol Pr -one another Protein Protein Ø When opposite charges are separated, system Protein has potential energy Ø Potential energy across a membrane can be measured by a voltage meter and gives the Dr. Pasan Fernando voltage at the membrane, ex. -70 mV 25  Electrochemical gradients § Both electrical and chemical forces act on ions Ex. Na+ § Na+ has a chemical (concentration) gradient that drives Na+ into the cell § Na+ has a smaller electrical gradient that also drives Na+ into the cell § Together, they form a large Na+ electrochemical gradient Ex. K+ § K+ has a chemical (concentration) gradient that drives K+ out of the cell § K+ is attracted to the negative charge inside the cell – this is the K+ electrical gradient that pulls K+ back into Dr. Pasan Fernando the cell § Together, the K+ electrochemical gradient works to drive K+ out of the cell – but it is weaker vs. Na+ Copyright © 2019 John Wiley & Sons, Inc. All rights reserved. Which of the following statements regarding the selective permeability of the lipid bilayer portion of the plasma membrane is FALSE? A. The permeability of the lipid bilayer to different substances varies. B. The lipid bilayer component of the plasma membrane is highly permeable to nonpolar molecules, such as oxygen (O2). C. The lipid bilayer component of the plasma membrane is moderately permeable to ions and large, uncharged polar molecules, such as glucose. Dr. Pasan Fernando D. The more hydrophobic or lipid-soluble a substance is, the greater the lipid bilayer’s permeability to that substance. 27 Copyright © 2019 John Wiley & Sons, Inc. All rights reserved. Which of the following statements regarding gradients across the plasma membrane is true? A. A difference in electrical charges between two regions constitutes a concentration gradient. B. Substances with similar charges are attracted to each other, while oppositely charged substances are repelled. C. An electrical gradient is a difference in the concentration of a chemical from one place to another. D. An electrochemical gradient is the combined influence of the concentration and electrical gradients on the movement of a particular ion. Dr. Pasan Fernando 28  Dr. Pasan Fernando 29  Overview of the nervous system Objectives § Describe the organization of the nervous system § Explain the functions of the nervous system Dr. Pasan Fernando  Organization of the nervous system Think of the CNS and PNS as anatomical differences Functionally, the CNS and PNS are similar Dr. Pasan Fernando  Organization of the nervous system Dr. Pasan Fernando  Functions of the nervous system Sensory § Sensory receptors detect external or internal stimuli, and relay sensory information to the brain and spinal cord for integration. Integration § CNS analyzes sensory information, and makes decisions for appropriate responses. Motor § Motor information is conveyed from the CNS through cranial and spinal nerves of the PNS to appropriate effectors (muscles and glands). Dr. Pasan Fernando  Cells of the nervous system Objectives § Discuss the structure and function of neurons § List the roles of neuroglia § Explain the importance of myelination § Describe the ability to repair neurons of the CNS and PNS Dr. Pasan Fernando  Components of a Neuron Dendrites Dendrites Presynaptic cell § Reception of incoming information Postsynaptic cell § Branch to junctions called synapses Cell body (soma) Axon Nucleus terminals Soma Axon hillock Direction of signal § Contains nucleus and most organelles Axon Axon hillock Presynaptic neuron § Where axon originates Synapse Dendrites § Where potentials are initiated Axon Axon terminal Postsynaptic neuron Neurotransmitter (after release) § Transmits electrical impulses called action Axon potentials terminals Axon Dr. Pasan Fernando Axon terminal (telodendria) Collateral § Releases neurotransmitter axon 35  Neuron Cell Body Dendrites Cell body § Also called the perikaryon or soma (receptive (biosynthetic center regions) and receptive region) § Biosynthetic center of neuron Ø Synthesizes proteins, membranes, chemicals Ø Rough ER (chromatophilic substance, or Nissl bodies) § Contains spherical nucleus with nucleolus Nucleus § In most neurons, plasma membrane is part of receptive region that receives input info from other neurons § Most neuron cell bodies are located in CNS Axon Nucleolus (impulse-generating Mye Ø Nuclei: clusters of neuron cell bodies in CNS Chromatophilic and conducting (nod Dr. Pasan Fernando region) substance (rough Ø Ganglia: clusters of neuron cell bodies in PNS endoplasmic reticulum) Axon Schwann hillock Impulse cell direction Term 36 branc  Neuron Processes - Axon Dendrites The axon: functional characteristics § Axon is the conducting region of neuron Cell body (soma) Axon Nucleus terminals § Generates nerve impulses and transmits them Direction of signal along axolemma (neuron cell membrane) to axon Axon hillock terminal Presynaptic neuron Axon Ø Terminal: region that secretes neurotransmitters, Synapse which are released into extracellular space Dendrites Ø Can excite or inhibit neurons it contacts Axon terminal § Carries on many conversations with different Neurotransmitter Postsynaptic neuron neurons at same time (after release) Axon § Axons rely on cell bodies to renew proteins and terminals Axon Dr. Pasan Fernando membranes Collateral axon 37  Neuron Processes - Axon Synaptic vesicle Kinesin § Axons have efficient internal transport mechanisms protein Microtubule Axon terminals Molecules and organelles are moved along axons by Smooth Golgi apparatus Ø endoplasmic reticulum Synaptic vesicle Nucleus (empty) motor proteins and cytoskeletal elements Rough endoplasmic reticulum § Movement occurs in both directions Transport Microtubule vesicles Synaptic vesicle (with neurotransmitters) Ø Anterograde: away from cell body – Examples: mitochondria, cytoskeletal elements, membrane components, enzymes Ø Retrograde: toward cell body – Examples: organelles to be degraded, signal molecules, viruses, and bacterial toxins Dr. Pasan Fernando 38  Cellular Products Need to Move in Neurons Neuron length 1 mm to > 1m Entire cell must be 'satisfied' as a cellular entity Energy, waste products need to be transported between cell body and axon terminals § Anterograde and retrograde transport § Slow axonal transport § Fast axonal transport § Rely on network of microtubule transport Dr. Pasan Fernando Ø See Lecture 3 – cellular components - cytoskeleton 39  Neuroglia Astrocytes § Most numerous § Help maintain blood-brain barrier § Maintain extracellular chemical environment § Guide neurons during development § Play role in synapse formation Oligodendrocytes § Form and maintain myelin sheath in CNS Microglia § Phagocytes Dr. Pasan Fernando Ø Remove: debris, damaged cells, and pathogens Ependymal cells § Produce and assist in the circulation of CSF  Neuroglia: PNS Schwann cell § Form and maintain myelin sheath in PNS § Participate in PNS axon regeneration Dr. Pasan Fernando  Myelination and Functions of the Myelin Sheath Electrical insulation § Increases speed of conduction of action potentials Found in both CNS and PNS § Schwann cell = PNS § Oligodendrocyte = CNS Nodes of Ranvier § Gaps in the myelination Makes up white matter Dr. Pasan Fernando  Neuron repair Plasticity vs. repair Plasticity § Ability to change throughout life Repair § Regeneration after damage Dr. Pasan Fernando  Regeneration: PNS Occurs if… § Cell body is still intact § Schwann cell remains active Schwann cells form regeneration tube § Guides and stimulates regrowth of the axon Dr. Pasan Fernando  Regeneration: CNS Little to none can occur § Possible reasons why Ø Inhibitory proteins released by neuroglia Ø Absence of growth stimulating cues Ø Scar tissue formation CNS damage tends to be permanent – although research now shows that CNS can repair in some instances Dr. Pasan Fernando  Dr. Pasan Fernando 46