Paramedicine – Medical Physiology I Lecture 3 PDF

PAR3623 Paramedicine – Medical Physiology I F2024 Lecture 3 Cellular basis of physiological function – Part III  Copyright / Intellectual Property Notice Materials posted to courses are subject to Intellectual Property and Copyright p...

PAR3623 Paramedicine – Medical Physiology I F2024 Lecture 3 Cellular basis of physiological function – Part III  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. Dr. Pasan Fernando  Lecture 3 Objectives for Lecture 3 § Describe different modes of membrane transport and identify their relevance to cellular function § List and compare the key features of the four major classes of cells in the body. § Describe the diversity in epithelial cells with respect to their structure and function. § Describe the modes of membrane transport related to epithelial cells. § Describe the cellular responses to stress § Distinguish between apoptosis and necrosis and describe the role of the plasma membrane in this process. Dr. Pasan Fernando 4  Membrane Transport Objectives: 1. Describe the principle of passive diffusion 2. Describe the principles of facilitated diffusion 3. Describe the processes of osmosis and the factors that affect osmosis Dr. Pasan Fernando 5  How do substances move across the plasma membrane? Plasma membranes are selectively permeable § Some molecules pass through easily; some do not Two ways substances cross membrane § Passive processes: no energy required – like pedaling downhill on a bicycle § Active processes: energy (ATP) required – like pedaling uphill on a bicycle Dr. Pasan Fernando  Passive Membrane Transport Passive transport requires no energy Two types of passive transport § Diffusion Ø Simple diffusion Ø Carrier- and channel-mediated facilitated diffusion Ø Osmosis (movement of a solvent (water in living systems) through a selectively permeable membrane i.e. directly across by simple diffusion or through a water channel by facilitated diffusion § Filtration Ø Type of transport that usually occurs across capillary walls Dr. Pasan Fernando 8  Diffusion § Collisions between molecules in areas of high concentration cause them to be scattered into areas with less concentration Ø Difference is called a concentration gradient Ø Diffusion is the movement of molecules down their concentration gradients (from high to low) – Energy is not required (but energy is often released) § Speed of diffusion is influenced by size of molecule and temperature § Molecules have natural drive to diffuse down concentration gradients that exist between extracellular and intracellular areas § Plasma membranes stop diffusion and create concentration gradients by acting as selectively permeable barriers Dr. Pasan Fernando Dye pellet Diffusion occurring Dye evenly distributed 9  Simple Diffusion Simple diffusion § Nonpolar lipid-soluble (hydrophobic) substances diffuse directly through phospholipid bilayer § Examples: oxygen, carbon dioxide, fat-soluble vitamins Dr. Pasan Fernando 10  Facilitated Diffusion Facilitated diffusion § Certain hydrophobic molecules (e.g., glucose, amino acids, and ions) are transported passively down their concentration gradient by: Ø Carrier-mediated facilitated diffusion – Substances bind to protein carriers Ø Channel-mediated facilitated diffusion – Substances move through water-filled channels Dr. Pasan Fernando 11  Facilitated Diffusion Carrier-mediated facilitated diffusion § Carriers are transmembrane integral proteins § Carriers transport specific polar molecules, such as sugars and amino acids, that are too large for membrane channels Ø Example of specificity: glucose carriers will carry only glucose molecules, nothing else § Binding of molecule causes carrier to change shape, moving molecule in process § Binding is limited by number of carriers present Ø Carriers are saturated when all are bound to molecules and are busy transporting Dr. Pasan Fernando 12  Facilitated Diffusion Channel-mediated facilitated diffusion Small lipid- § Channels with aqueous-filled cores are formed by insoluble transmembrane proteins solutes § Channels transport molecules such as ions or water (osmosis) down their concentration gradient Ø Specificity based on pore size and/or charge Ø Water channels are called aquaporins § Two types: Ø Leak channels – Always open Ø Gated channels – Controlled by chemical or electrical signals Dr. Pasan Fernando 13 Channel-mediated facilitated diffusion through a channel protein; mostly ions selected on basis of size and charge  Diffusion - Osmosis Osmosis Water § Movement of solvent, such as water, across a selectively molecules permeable membrane § Water diffuses through plasma membranes Ø Through lipid bilayer (even though water is polar, it is so small that some molecules can sneak past nonpolar phospholipid tails) Ø Through specific water channels called aquaporins Lipid (AQPs) bilayer § Flow occurs when water concentration (from the suspended solvents) is different on the two sides of a membrane Dr. Pasan Fernando Aquaporin 14 Osmosis, diffusion of a solvent such as water through a specific channel protein (aquaporin) or through the lipid bilayer  Diffusion - Osmosis § Osmolarity: measure of total concentration of solute particles § Water concentration varies with number of solute particles because solute particles displace water molecules Ø When solute concentration goes up, water concentration goes down, and vice versa § Water moves by osmosis from areas of low solute (high water) concentration to high areas of solute (low water) concentration Dr. Pasan Fernando 15  Diffusion - Osmosis When solutions of different osmolarity are separated by a membrane permeable to all molecules, both solutes and water cross membrane Membrane permeable to both solutes and water until equilibrium Solute is andreached water molecules move down their concentration gradients in opposite directions. Fluid volume remains the same in both compartments. § Equilibrium: Same concentration Right of solutes and water molecules on both sides, Left with equal volume on both sides compartment: compartment: Solution with Solution with Both solutions have the lower osmolarity greater osmolarity same osmolarity: volume unchanged H2O Solute Dr. Pasan Fernando Freely Solute permeable molecules membrane (sugar) 16  Diffusion - Osmosis When solutions of different osmolarity are separated by a membrane that is permeable only to water, not solutes, osmosis will occur until equilibrium isMembrane reached permeable to water, impermeable to solutes § In this instance, water moves Solute molecules across tofrom are prevented balance movingthe butosmolarity water moves orbyconcentration osmosis. of Volume increases particles on each side in the compartment with the higher osmolarity. Both solutions have identical § Same concentration of solutes and water molecules on both osmolarity, sides,ofwith but volume the unequal volumes on Left both sides Right solution on the right is greater because only water is compartment compartment free to move H2O Dr. Pasan Fernando Selectively Solute permeable molecules membrane (sugar) 17  Diffusion - Tonicity Tonicity § Ability of a solution to change the shape or tone of cells by altering the cells’ internal water volume Ø Isotonic solution has same osmolarity as inside the cell, so volume remains unchanged Ø Hypertonic solution has higher osmolarity than inside cell, so water flows out of cell, resulting in cell shrinking – Shrinking is referred to as crenation Ø Hypotonic solution has lower osmolarity than inside cell, so water flows into cell, resulting in cell Isotonic solutions Hypertonic solutions Hypotonic solutions swelling Cells retain their normal size and Cells lose water by osmosis and Cells take on water by osmosis shape in isotonic solutions (same shrink in a hypertonic solution until they become bloated and – Can lead to cell bursting, referred to as lysing solute/water concentration as inside cells; water moves in (contains a higher concentration of nonpenetrating solutes than burst (lyse) in a hypotonic solution (contains a lower and out). are present inside the cells). concentration of nonpenetrating solutes than are present inside cells). Dr. Pasan Fernando 18  The Pensive Paramedic Draw a cell that is surrounded by a hypertonic solution Indicate the direction of water movement What mechanism(s) explain the direction of water movement? Can the solutes in the solution or the cell move? Dr. Pasan Fernando 19  Dr. Pasan Fernando 20  Active Transport Objectives: § Describe how primary active transport occurs. § Provide specific examples of secondary active transport. Dr. Pasan Fernando 21  Active Transport The movement of substances across a membrane against their concentration or electrochemical gradient Primary active transport § Uses ATP Secondary active transport § Uses energy stored in an electrochemical gradient to drive other solutes Dr. Pasan Fernando 22  Primary active transport Energy derived from the hydrolysis of ATP changes the shape of a carrier protein (pump) to move a solute across a plasma membrane against its concentration or electrochemical gradient Dr. Pasan Fernando  Secondary active transport (1 of 2) Energy stored in the electrochemical gradient of an ion is used as energy to drive other solutes across the plasma membrane against their own concentration or electrochemical gradients. Dr. Pasan Fernando  Secondary active transport Dr. Pasan Fernando  Vesicular transport (1 of 2) Objectives: § Describe the different types of endocytosis. § Explain how exocytosis occurs. Dr. Pasan Fernando  Vesicular transport Vesicles are formed § Two types Ø Endocytosis Ø Exocytosis Dr. Pasan Fernando  Receptor mediated endocytosis § Highly selective § Cells take up specific ligands § Ligand binds to a specific plasma membrane receptor and vesicle forms Dr. Pasan Fernando  Phagocytosis § A form of endocytosis in which the cell engulfs large solid particles such as a bacterium Dr. Pasan Fernando  Bulk phase endocytosis Also called pinocytosis § A form of endocytosis where tiny bits of extracellular fluid are taken up Dr. Pasan Fernando  Exocytosis § Used to release materials from a cell. Dr. Pasan Fernando  Dr. Pasan Fernando 32  Cell Types of the Body Objective ü Compare and contrast the four cell types Dr. Pasan Fernando 33  Overview Of Major Cell Types In Body § There are over 200 cell types in the Skeletal muscle cell body Smooth muscle cells Cardiac muscle cells § Four major classes: Muscle cells Ø Neurons Blood cells Ø Muscle cells Ø Epithelial cells Basement Ø Connective cells membrane Bone cells Basement membrane § Together these make the four main Lumen types of tissues in the body Dr. Pasan Fernando Basement membrane Fibroblasts Epithelial cells (in skin and other tissues) Connective tissue cells 34  Neurons and Neural Tissue § Specialized to carry information or instructions NEURAL TISSUE within the body § Two basic types of cells Conducts electrical impulses Carries information 1. Neurons (nerve cells) Neurons Neuroglia – Transmit information in form of electrical impulses 2. Neuroglia (supporting cells) – Isolate and support neurons – Form supporting framework § Two locations within the body 1. Central nervous system – Brain and spinal cord Dr. Pasan Fernando 2. Peripheral nervous system – Nerves connect central nervous system with other tissues and organs 35  Muscle Cells and Muscle Tissue § Contract to generate mechanical force and Skeletal muscle cell movement § Electrical signals à mechanical force Smooth muscle cells Cardiac muscle cells § Voluntary – skeletal muscles (arms, legs) § Non-voluntary – cardiac, smooth muscle Muscle cells (blood vessels) Dr. Pasan Fernando APSUbiology.org 36  Connective cells and connective tissue Blood cells § Most diverse of the four cell types § Has extracellular matrix § Functions to anchor, attach body structures § Bone, tendons, fat, blood Bone cells Fibroblasts Dr. Pasan Fernando (in skin and other tissues) Connective tissue cells 37  Epithelial Cells and Epithelial Tissue § Epithelium – sheet-like layer of cells § Forms lining of internal body surfaces & cavities § Forms lining of hollow organs Ø blood vessels have specialized epithelium called endothelium Ø lumen = interior Basement membrane Major function as a barrier § Provides protection Form glandular tissue Basement membrane § Produce compounds related to body function § Exocrine glands have ducts Lumen Ø Sweat, salivary § Endocrine glands no ducts Basement Dr. Pasan Fernando Ø Pituitary, thyroid, adrenal membrane Epithelial cells 38  Epithelial Cells - Exocrine and Endocrine Glands External environment External environment Epithelium Blood vessel Secretory Duct cells Blood flow Secretory cells Hormone Exocrine gland Endocrine gland Exocrine glands Endocrine glands Dr. Pasan Fernando Products collect and released into duct Direct release into bloodstream Eg. sweat, saliva, tears Pituitary, thyroid, hypothalamus 39  Characteristics of Epithelial Cells Objective: ü Identify and describe the different types of epithelial cells within the body ü Describe the different types of cell attachments and provide examples of where they’re found. Dr. Pasan Fernando 40  Epithelial Cells Naming convention § All epithelial cells have two names § First indicates number of cell layers (simple or stratified) § Second indicates shape (squamous, cuboidal, columnar) § Shape can vary in a stratified layer Two surfaces: § Apical surface faces the external environment § Basal surface faces the internal environment Dr. Pasan Fernando 41  Epithelial Cells - Squamous Simple epithelia § Important in absorption, secretion, filtration Simple squamous epithelium § Cells flatten laterally, thin cytoplasm § Important where rapid diffusion of cellular material is needed, E.g. lungs, kidney Two types of simple squamous epithelia are named based on location § Endothelium – lining of vessels, lines heart § Mesothelium – lines serous membranes in ventral body cavity Ø Parietal mesothelium lines body walls Dr. Pasan Fernando Ø Mesothelium lining internal organs is the visceral mesothelium 42  Epithelial Cells - Cuboidal Simple cuboidal epithelium Description: Single layer of cubelike cells with large, spherical central nuclei. Simple cuboidal epithelial cells Simple cuboidal epithelium Nucleus § Single layer of cells § Involved in secretion and Function: Secretion and absorption. Basement absorption membrane § Forms walls of smallest ducts of Location: Kidney tubules; glands and many kidney tubules ducts and secretory portions Connective of small glands; ovary surface. tissue Photomicrograph: Simple cuboidal epithelium in kidney tubules (430 ). Dr. Pasan Fernando 43  Epithelial Cells - Columnar Simple columnar epithelium Simple columnar epithelium Description: Single layer of tall cells with round to oval nuclei; many cells bear microvilli, some bear cilia; § Single layer of tall, closely packed cells layer may contain mucus-secreting unicellular glands (goblet cells). Microvilli Ø Some cells have microvilli, and some have cilia Simple columnar Ø Some layers contain mucus-secreting epithelial cell goblet cells Function: Absorption; secretion Mucus of of mucus, enzymes, and other § Involved in absorption and secretion of substances; ciliated type propels mucus (or reproductive cells) by goblet cell mucus, enzymes, and other substances ciliary action. Location: Nonciliated type lines Ø Ciliated cells move mucus most of the digestive tract (stomach to rectum), gallbladder, and excretory Photomicrograph: Simple columnar § Found in digestive tract, gallbladder, ducts of some glands; ciliated variety lines small bronchi, uterine tubes, epithelium of the small intestine mucosa ducts of some glands, bronchi, and and some regions of the uterus. (640 ). uterine tubes Dr. Pasan Fernando © 2017 Pearson Education, Inc. 44  Epithelial Cells - Pseudostratified Pseudostratified columnar epithelium Description: Single layer of cells of differing heights, some not Goblet cell (contains Pseudostratified columnar reaching the free surface; nuclei seen at different levels; may mucus) contain mucus-secreting cells and Cilia epithelium bear cilia. § Cells vary in height Pseudo- stratified § Appear multi-layered but is actually a epithelial layer single layered simple epithelium Function: Secrete substances, particularly mucus; propulsion of mucus by ciliary action. § Cells are often ciliated Location: Nonciliated type in Basement males’ sperm-carrying ducts and § Involved in secretion, movement via ducts of large glands; ciliated variety lines the trachea, most of Photomicrograph: Pseudostratified ciliated membrane the upper respiratory tract. columnar epithelium lining the human trachea ciliary action (780 ). § Found in upper respiratory tract, ducts Trachea of large glands Dr. Pasan Fernando 45  Epithelial Cells - Stratified Stratified squamous epithelium Stratified epithelial tissues Description: Thick membrane composed of several cell layers; § Consist of two or more layers of cells basal cells are cuboidal or columnar and metabolically active; surface § New cells regenerate from the basal cells are flattened (squamous); in the keratinized type, the surface cells are surface, migrate toward apical surface full of keratin and dead; basal cells are active in mitosis and produce the Stratified cells of the more superficial layers. squamous § More durable than simple epithelium epithelia…..function is….?? Stratified squamous epithelium Nuclei Function: Protects underlying Basement § Most common type of stratified epithelia tissues in areas subjected to membrane abrasion. Connective § Apical surface is squamous, deeper layers Location: Nonkeratinized type forms the moist linings of the esophagus, tissue are cuboidal or columnar mouth, and vagina; keratinized variety forms the epidermis of the skin, a dry Photomicrograph: Stratified squamous epithelium lining the esophagus (285 ). membrane. § Found in tissues prone to wear and tear (e.g. skin) Dr. Pasan Fernando 46  Epithelial Cells – Transitional Transitional epithelium Description: Resembles both stratified squamous and stratified cuboidal; basal cells § Forms lining of hollow urinary cuboidal or columnar; surface cells dome shaped or organs squamouslike, depending on degree of organ stretch. § E.g. bladder, ureters, urethra § Has basal layer of cuboidal or columnar cells Transitional epithelium § Cells can change shape when stretched – accommodates Function: Stretches readily, Basement tissue function permits stored urine to distend membrane urinary organ. § E.g. bladder expansion Location: Lines the ureters, Photomicrograph: Transitional epithelium Connective tissue bladder, and part of the urethra. lining the bladder, relaxed state (360 ); note the bulbous, or rounded, appearance of the cells at the surface; these cells flatten and Dr. Pasan Fernando elongate when the bladder fills with urine. 47  Dr. Pasan Fernando 48  Transepithelial transport Objectives § Define transepithelial transport. § Describe the difference between absorption and secretion. § Explain how transcytosis occurs. Dr. Pasan Fernando  Overview of transepithelial transport § Movement of solutes across epithelial cells. Dr. Pasan Fernando  Epithelial cell - Absorption vs. secretion Absorption § When a solute moves from the lumen of an organ into the bloodstream Secretion § When a solute moves from the bloodstream into the lumen of an organ Dr. Pasan Fernando  Epithelial cell - Transcytosis § Transport using vesicles to move a substance successively into, across, and out of a cell Dr. Pasan Fernando  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 cells can be bound to each other § Tight junctions § Desmosomes § Gap junctions Dr. Pasan Fernando  Cell Junctions – Tight junctions Plasma membranes Microvilli of adjacent cells Tight junctions Intercellular § Integral proteins on adjacent space cells fuse to form an impermeable junction that encircles whole cell § Prevent fluids and most Basement membrane molecules from moving in between cells Interlocking Dr. Pasan Fernando junctional proteins Intercellular space 54 Tight junctions: Impermeable junctions that form continuous seals around the cells prevent molecules from passing through the intercellular space.  Cell Junctions - Desmosomes Plasma membranes Microvilli of adjacent cells Desmosomes § Rivet-like cell junction formed when linker Intercellular space proteins (cadherins) of neighboring cells interlock like the teeth of a zipper § Linker protein is anchored to its cell through thickened “button-like” areas on inside of plasma membrane called plaques Basement membrane § Keratin filaments connect plaques Intercellular space intercellularly for added anchoring strength Plaque § Desmosomes allow “give” between cells, reducing the possibility of tearing under tension Dr. Pasan Fernando § Where might these be useful in body? Linker proteins Intermediate (cadherins) filament (keratin) Desmosomes: Anchoring junctions 55 that bind adjacent cells together act like molecular “Velcro” and also help form an internal tension-reducing network of fibers.  Cell Junctions – Gap junctions Plasma membranes Microvilli of adjacent cells Gap junctions Intercellular space § Transmembrane proteins (connexons) form tunnels that allow small molecules to pass from cell to cell § Used to spread ions, simple sugars, or other small molecules between cells Basement membrane § Allows electrical signals to be passed quickly from one cell to next cell Intercellular space Ø Used in cardiac and smooth muscle cells Channel between cells (formed by connexons) Dr. Pasan Fernando Gap junctions: Communicating 56 junctions that allow ions and small molecules to pass are particularly important for communication in heart cells and embryonic cells.  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 57  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 59  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 60  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 61  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 64  Which membrane proteins are necessary for cellular communication? Compare the advantages and disadvantages of simple squamous epithelium What types of tissues/organs or locations in the body require a stratified epithelial layer of cells? Describe the components of cell adhesions. Why are they needed in tissues? Identify the tissues where they are found. Describe their role in supporting cellular homeostasis. Dr. Pasan Fernando Contrast between apoptosis and necrosis. Which type of cell death supports homeostasis. Explain your thinking. 65  Dr. Pasan Fernando 66