PHARM. 181: Introduction to Human Anatomy & Physiology I PDF

PHARM. 181: INTRODUCTION TO HUMAN ANATOMY & PHYSIOLOGY I Charles Ansah, PhD; FPCPharm; FGHCPharm Professor of Pharmacology & Toxicology/Former Dean & Pro Vice-Chancellor Room C118 Tackie Building Department of Pharmacology Faculty of Pharmacy & Pharmaceutical Sciences College of Health Scienc...

PHARM. 181: INTRODUCTION TO HUMAN ANATOMY & PHYSIOLOGY I Charles Ansah, PhD; FPCPharm; FGHCPharm Professor of Pharmacology & Toxicology/Former Dean & Pro Vice-Chancellor Room C118 Tackie Building Department of Pharmacology Faculty of Pharmacy & Pharmaceutical Sciences College of Health Sciences KNUST  Cellular level of organization Lecture Topic Cellular Level Of Organization Overview of the Cellular Basis of Life The Plasma Membrane: Structure The Plasma Membrane: Functions The Cytoplasm The Nucleus Cell Growth and Reproduction Clinical Applications Objectives Appreciate the cell as the basic functional unit of life Describe the structure of the plasma membrane and explain its functional significance. Describe the structure of the cell nucleus and explain its significance. Describe the structure & function of the cellular organelles in the cytoplasm. Describe the various processes of transport across the cell membrane. Describe the different stages of the cell cycle and list the events that occur in the different phases of mitosis. The Position of the Cell at the Organismal level Cellular Level of Organization The cell: Basic, living, structural and functional unit of life Organismal activity depends on individual and collective activity of cells Biochemical activities dictated by subcellular structure.  General functions of the cell Compartmentalization of biochemical reactions within specialized structures Regulate inflow & outflow of materials Use genetic material to direct cell activities Continuity of life originates from the cell  Cellular Diversity 100 trillion cells in the body -- 200 different types Vary in size and shape related to their function Parts of a cell The cell can be subdivided into 3 parts: 1. Plasma (cell) membrane 2. Cytoplasm Cytosol Organelles 3. Nucleus Chromosomes Genes  A typical cell Not all cells contain all of these organelles.  Plasma membrane (PM): Flexible but sturdy barrier that surround cytoplasm of cell. Fluid Mosaic Model: describes the PM as: Double (Bilayer) layer of lipids with imbedded, dispersed proteins -lipid is barrier to entry or exit of polar substances -proteins are “gatekeepers” -- regulate traffic Bilayer consists of phospholipids, cholesterol, and glycolipids -Glycolipids are lipids with bound carbohydrate -Phospholipids have hydrophobic and  Lipid Bilayer of the Cell Membrane Two back-to-back layers of 3 types of lipid molecules Cholesterol and glycolipids scattered among a double row of phospholipid molecules  Phospholipids Comprises 75% of lipids Phospholipid bilayer = 2 parallel layers of molecules Each molecule is amphipathic (has both a polar & non-polar region) –polar parts (heads) are hydophilic and face on both surfaces a watery environment –nonpolar parts (tails) are hydrophobic and line up next to each other in the interior Glycolipids within the Cell Membrane Comprises 5% of the lipids of the cell membrane Carbohydrate groups form a polar head only on the side of the membrane facing the extracellular fluid  Cholesterol within the Cell Membrane Comprises 20% of cell membrane lipids Interspersed among the other lipids in both layers Stiff steroid rings & hydrocarbon tail are non-polar and hide in the middle of the cell membrane  Types of Membrane Proteins Integral proteins Extend into or completely across cell membrane -if extend completely across = transmembrane proteins Glycoproteins have the sugar portion facing the extracellular fluid to form a glycocalyx –gives cell “uniqueness”, creates a stickiness to hold it to other cells or so it can hold a fluid layer creating a slippery surface Peripheral proteins –attached to either inner or outer surface of cell membrane and are easily removed from it Membrane Proteins Integral versus Peripheral Proteins Functions of Membrane Proteins (I)  Summary of functions of membrane proteins (I) Formation of Channel -passageway to allow specific substance to pass through Transporter Proteins -bind a specific substance, change their shape & move it across membrane Receptor Proteins -cellular recognition site -- bind to substance  Functions of Membrane Proteins (2)  Summary of functions of membrane proteins (2) Cell Identity Marker –allow cell to recognize other similar cells Linker –anchor proteins in cell membrane or to other cells –allow cell movement –cell shape & structure Act as Enzyme –speed up reactions  Membrane Fluidity Membranes are fluid structures (oil layer) –self-sealing if punctured with needle –membrane molecules can rotate & move freely difficult for hydrophilic parts to pass through hydrophobic core of bilipid layer –fluidity is reduced by presence of cholesterol increases stiffness of membrane as it forms hydrogen bonds with neighboring phospholipid heads  Selective Permeability of Membrane Lipid bilayer –permeable to non-polar, uncharged molecules -- oxygen, CO2, steroids –permeable to water which flows through gaps that form in hydrophobic core of membrane as phospholipids move about Transmembrane proteins act as specific channels –small and medium polar & charged particles Macromolecules unable to pass through the membrane –vesicular transport Gradients Across the Plasma Membrane Membrane can maintain difference in concentration of a substance inside versus outside of the membrane (concentration gradient) –more O2 & Na+ outside of cell membrane –more CO2 and K+ inside of cell membrane Membrane can maintain a difference in charged ions between inside & outside of membrane (electrical gradient or membrane potential) Together, these gradients make up an electrochemical gradient Thus, substances move down their concentration gradient and towards the oppositely charged area  Gradients Across Membrane Concentration gradient Electrical gradient Transport Across the Plasma Membrane Transport processes that move substances across the cell membrane are: Passive processes Simple diffusion Facilitated diffusion Osmosis Active processes Active transport Vesicular transport  Transport across membranes: –Mediated transport moves materials with the help of a transporter protein –Non-mediated transport does not use a transporter protein –active transport uses ATP to drive substances against their concentration gradients –passive transport moves substances down their concentration gradient with only their kinetic energy –vesicular transport move materials across membranes in small vesicles -- either by exocytosis or endocytosis  Diffusion Through the Lipid Bilayer Important for absorption of nutrients -- excretion of wastes Non-polar, hydrophobic molecules –oxygen, carbon dioxide, nitrogen, fatty acids, steroids, small alcohols, –ammonia and fat-soluble vitamins (A, E, D and K)  Diffusion Through Membrane Channels Each membrane channel specific for particular ion (K+, Cl-, Na+ or Ca2+) Slower than diffusion through membrane but still 1million K+ through a channel in one second Channels may be open all the time or gated (closed randomly or as ordered)  Transport Processes Interactions Animation: ▪ Transport Across the Plasma Membrane You must be connected to the Internet and in Slide show Mode to run this animation. Passive Processes  Simple Diffusion Crystal of dye placed in a cylinder of water Net diffusion from the higher dye concentration to the region of lower dye Equilibrium has been reached in the far right cylinder Diffusion is influenced by: 1. Steepness of the concentration gradient 2. Temperature 3. Mass of diffusion substance 4. Surface area 5. Diffusion distance  Principles of Diffusion Random mixing of particles in a solution as a result of the particle’s kinetic energy –more molecules move away from an area of high concentration to an area of low concentration the greater the difference in concentration between the 2 sides of the membrane, the faster the rate of diffusion the higher the temperature, the faster the rate of diffusion the larger the size of the diffusing substance, the slower the rate of diffusion an increase in surface area, increases the rate of diffusion increasing diffusion distance, slows rate of diffusion When the molecules are evenly distributed, equilibrium has been reached  Facilitated Diffusion Transmembrane proteins help solutes that are too polar or too highly charged move through the lipid bilayer The processes involved are: Channel mediated facilitated diffusion Carrier mediated facilitated diffusion  Facilitated Diffusion Substance binds to specific transporter protein Transporter protein conformational change moves substance across cell membrane Facilitated diffusion occurs down concentration gradient only –if no concentration difference exists, no net movement across membrane occurs Rate of movement depends upon –steepness of concentration gradient –number of transporter proteins (transport maximum)  Facilitated Diffusion of Glucose Glucose binds to transport protein Transport protein changes shape Glucose moves across cell membrane (but only down the concentration gradient) Kinase enzyme reduces glucose concentration inside the cell by transforming glucose into glucose-6-phosphate Transporter proteins always bring glucose into cell Channel Mediated Facilitated Diffusion Carrier Mediated Facilitated Diffusion Diffusion: A Comparison  Osmosis Net movement of water through a selectively permeable membrane from an area of high water concentration to an area of lower water concentration –diffusion through lipid bilayer –aquaporins (transmembrane proteins) that function as water channels Only occurs if membrane is permeable to water but not to certain solutes  Osmosis of Water Through a Membrane Pure water on the left side & a membrane impermeable to the solute Net movement of water is from left to right, until hydrostatic pressure (osmotic pressure ) starts to push water back to the left Tonicity of a solution relates to how the solution influences the shape of body cells Effects of Tonicity on RBCs in Lab Normally the osmotic pressure inside of the cell is equal to the fluid outside the cell –cell volume remains constant (solution is isotonic) Effects of fluids on RBCs in lab –water enters the cell faster than it leaves –water enters & leaves the cell in equal amounts –water leaves the cell  Effects of Tonicity on Cell Membranes Isotonic solution –water concentration the same inside & outside of cell results in no net movement of water across cell membrane Hypotonic solution –higher concentration of water outside of cell results in hemolysis Hypertonic solution –lower concentration of water outside of cell causes crenation Active Processes  Active Transport Movement of polar or charged substances against their concentration gradient –energy-requiring process energy from hydrolysis of ATP (primary active transport) energy stored in an ionic concentration gradient (secondary active transport) Exhibits transport maximums and saturation Na+, K+, H+, Ca2+, I- and Cl-, amino acids and monosaccharides Primary Active Transport Energy derived from ATP changes the shape of a transporter protein which pumps a substance across a plasma membrane against its concentration gradient  Primary Active Transport Transporter protein called a pump –works against concentration gradient –requires 40% of cellular ATP Na+/K+ ATPase pump most common example –all cells have 1000s of them –maintains low concentration of Na+ and a high concentration of K+ in the cytosol –operates continually Maintenance of osmotic pressure across membrane –cells neither shrink nor swell due to osmosis & osmotic pressure sodium continually pumped out as if sodium could not enter the cell (factor in osmotic pressure of extracellular fluid) K+ inside the cell contributes to osmotic pressure of cytosol  Na+/K+ Pump & ATP As Its Energy Source 1. Na+ Binding 2. ATP split, 3Na+ ions pushed out 3. Na+ ions removed from cell as 2 K + brought into cell. 4. K+ binding 5. Phosphate release 6. K+ is pushed in  Secondary Active Transport Uses energy stored in an ion concentration gradient to move other substances against their own concentration gradient Na+/K+ pump maintains low concentration of Na+ inside of cells –provide route for Na+ to leak back in and use energy of motion to transport other substances –Na+ symporter proteins glucose or amino acids rush inward with Na+ ions –Na+ antiporters protein as Na+ ions rush inward, Ca2+ or H+ pushed out Secondary Active Transport Energy stored (in a hydrogen or sodium concentration gradient) is used to drive other substances against their own concentration gradients Antiporters and Symporters One in & one out. Both going in  Digitalis Slows the sodium pump, which lets more Na+ accumulate in heart muscle cells. Less Na+ concentration gradient across the membrane Na+/Ca2+ antiporters slow down so more Ca2+ remains inside the cardiac cells Strengthening the force of contraction Balance between concentration of Na+ and Ca2+ in cytosol & extracellular fluid is important Vesicular Transport of Particles Exocytosis = release something from cell Vesicles form inside cell, fuse to cell membrane Release their contents –digestive enzymes, hormones, neurotransmitters or waste products  Vesicular Transport of Particles Endocytosis = bringing something into cell –phagocytosis = cell eating by macrophages & WBCs particle binds to receptor protein whole bacteria or viruses are engulfed & later digested –pinocytosis = cell drinking no receptor proteins –receptor-mediated endocytosis = selective input mechanism by which HIV virus enters cells Active Transport in Vesicles: Receptor- mediated Endocytosis Mechanism for uptake of specific substances -- ligands Desired substance binds to receptor protein in clathrin- coated pit region of cell membrane causing membrane to fold inward Vesicles become uncoated & combine with endosome Receptor proteins separate from ligands and return to surface Ligands are digested by lysosomal enzymes Active Transport in Vesicles: Phagocytosis Active Transport in Vesicles: Bulk Phase Endocytosis (Pinocytosis)  Pinocytosis and Phagocytosis No pseudopods form Pseudopods extend to Nonselective drinking of form phagosome extracellular fluid Lysosome joins it Active Transport in Vesicles: Exocytosis & Transcytosis Exocytosis – membrane-enclosed secretory vesicles fuse with the plasma membrane and release their contents into the extracellular fluid Transcytosis – a combination of endocytosis and exocytosis used to move substances from one side of a cell, across it, and out the other side A Comparison of Transport Types A Comparison of Transport Types Cell organelles  Cell Organelles Nonmembranous organelles lack membranes & are indirect contact with cytoplasm Membranous organelles surrounded by one or two lipid bilayer membranes Cytoplasm Cytosol is also known as the intracellular fluid portion of the cytoplasm Organelles are the specialized structures that have specific shapes and perform specific functions Cytosol = Intracellular fluid 55% of cell volume 75-90% water with other components – large organic molecules (proteins, carbos & lipids) suspended by electrical charges –small organic molecules (simple sugars) & ions dissolved –inclusions (large aggregates of one material) lipid droplets glycogen granules Site of many important chemical reactions –production of ATP, synthesis of building blocks Cytoskeleton Network of protein filaments throughout the cytosol Functions –cell support and shape –organization of chemical reactions –cell & organelle movement Continually reorganized Cytoskeleton The Cytoskeletonal Filaments Microfilaments –thinnest filaments (actin) –locomotion & division –support microvilli Intermediate filaments –several different proteins –anchor organelles Microtubules –large cylindrical structures (composed of tubulin) –flagella, cilia & centrosomes  Centrosome Found near nucleus Pericentriolar area –formation site for mitotic spindle and microtubules Centrosome –2 centrioles(90 degrees to each other) –9 clusters of 3 microtubules –role in formation of cilia & flagella  Ribosomes Free ribosomes are loose in cytosol –synthesize proteins found inside the cell Membrane-bound ribosomes –attached to endoplasmic reticulum or nuclear membrane –synthesize proteins needed for plasma membrane or for export –10 to 20 together form a polyribosome Inside mitochondria, synthesize mitochondrial proteins Ribosomal Subunits Large + small subunits –made in the nucleolus –assembled in the cytoplasm Endoplasmic Reticulum Network of membranes forming flattened sacs or tubules called cisterns –half of membranous surfaces within cytoplasm Rough ER –continuous with nuclear envelope & covered with attached ribosomes –synthesizes, processes & packages proteins for export –free ribosomes synthesize proteins for local use Smooth ER -- no attached ribosomes –synthesizes phospholipids, steroids and fats –detoxifies harmful substances (alcohol) Rough ER is covered with fixed ribosomes. Golgi Complex 3-20 flattened, curved membranous sacs called cisterns Convex side faces ER & concave side faces cell membrane Processes & packages proteins produced by rough ER  Packaging by Golgi Complex Proteins pass from rough ER to golgi complex in transport vesicles Processed proteins pass from entry cistern to medial cistern to exit cistern in transfer vesicle Finished proteins exit golgi as secretory, membrane or storage vesicle (lysosome)  Cystic Fibrosis Deadly inherited disorder Chloride ion pump protein is not properly secreted from the golgi or rough ER Result is an imbalance in the transport of fluid and ions across the plasma membrane –buildup of thick mucus outside of certain cells respiratory and digestive problems Lysosomes Membranous vesicles –formed in Golgi complex –filled with digestive enzymes –pumps in H+ ions until internal pH reaches 5.0 Functions –digest foreign substances recycles own organelles –autolysis lysosomal damage after death  Tay-Sachs Disorder Affects children of eastern European- descent –seizures, muscle rigidity, blind, demented and dead before the age of 5 Genetic disorder caused by absence of single lysosomal enzyme –enzyme normally breaks down glycolipid commonly found in nerve cells –as glycolipid accumulates, nerve cells lose functionality –chromosome testing now available  Peroxisomes Membranous vesicles –smaller than lysosomes –form by division of preexisting peroxisomes –contain enzymes that oxidize organic material Function –part of normal metabolic breakdown of amino acids and fatty acids –oxidizes toxic substances such as alcohol and formaldehyde –contains catalase which decomposes H 2O2 Mitochondria Double membrane organelle –central cavity known as matrix –inner membrane folds known as crista surface area for chemical reactions of cellular respiration Function –generation of ATP –powerhouse of cell Mitochondria self-replicate –increases with need for ATP  Nucleus Large organelle with double membrane nuclear envelope –outer membrane continuous with rough ER –perforated by water-filled nuclear pores Nucleolus –spherical, dark bodies within the nucleus (no membrane) –site of ribosome assembly Function of Nucleus 46 human DNA chromosomes –genes found on chromosomes –gene directs synthesis for a specific protein Non-dividing cells contain nuclear chromatin – loosely packed DNA Dividing cells contain chromosomes –tightly packed DNA –it doubles (copied itself) before condensing  Protein Synthesis Instructions for making specific proteins is found in the DNA (your genes) –transcribe that information onto a messenger RNA molecule each sequence of 3 nucleotides in DNA is called base triplet each base triplet is transcribed as 3 RNA nucleotides (codon) –translate the “message” into a sequence of amino acids in order to build a protein molecule  Transcription DNA sense strand is template for the creation of messenger RNA strand Translation Process where mRNA, rRNA & tRNA are used to form a specific protein  Normal Cell Division Mitosis (somatic cell division) –one parent cell gives rise to 2 identical daughter cells mitosis is nuclear division cytokinesis is cytoplasmic division –occurs in billions of cells each day –needed for tissue repair and growth Meiosis (reproductive cell division) –egg and sperm cell production –in testes and ovary only  The Cell Cycle in Somatic Cells Process where cell duplicates its contents & divides in two –23 homologous pairs of chromosomes must be duplicated –genes must be passed on correctly to the next generation of cells Nuclear division = mitosis –continuous process divided into 4 stages –prophase, metaphase, anaphase & telophase Cytoplasmic division = cytokinesis  Interphase Stage of Cell Cycle Doubling of DNA and centrosome Phases of interphase stage -- G1, S, and G2 –G1 = cytoplasmic increase (G0 if never divides again) –S = replication of chromosomes –G2 = cytoplasmic growth  Replication of Chromosomes Doubling of genetic material during interphase. (S phase) DNA molecules unzip Mirror copy is formed along each old strand. Nitrogenous bases pick up complementary base 2 complete identical DNA molecules formed Stages of Nuclear Division:Mitosis Prophase Metaphase Anaphase Telophase  Prophase Chromatin condenses into visible chromosomes –pair of identical chromatids held together by a centromere Nucleolus & nuclear envelope disappear Each centrosome moves to opposite ends of cell –forms a mitotic spindle with 3 types of microtubules those that bind to kinetochore protein on centromere those that radiate outward those that extend between the 2 centrosomes –spindle is responsible for the separation of chromatids to each new daughter cell Metaphase Chromatid pairs line up across the middle of cell at the metaphase plate Anaphase Chromatids (daughter chromosomes) move toward opposite poles of cell –movement is due to shortening of microtubules Chromosomes appear V-shaped as they are dragged towards the poles of the cell –pull is at centromere region Telophase Chromosomes stop moving & appear as dark, condensed bundle Chromosomes uncoil & revert to chromatin Nucleoli and nuclear membrane reappear Mitotic spindle breaks up Cytokinesis Division of cytoplasm and organelles Begins in late anaphase with formation of cleavage furrow –indentation of cell membrane by actin microfilaments just inside plasma membrane –furrow always perpendicular to the mitotic spindle so chromosomes will be separated properly Ends with 2 daughter cells in interphase  Control of Cell Destiny Cell destiny is either to remain alive & functioning, to grow & divide or to die Homeostasis must maintain balance between cell multiplication & cell death The protein cyclin builds up during interphase and triggers mitosis Programmed cell death (apoptosis) occurs if a triggering agent turns on suicide enzymes that kills the cell Necrosis is cell death caused by injury or infection  Aging Age alters the body’s ability to adapt to changes in the environment Theories to explain aging –cells have a limited number of divisions –glucose bonds irreversibly with proteins – free radical theory---electrically charged molecules with an unpaired electron cause cell damage –autoimmune responses due to changes in cell identity markers Evidence of aging –damaged skin, hardened arteries, stiff joints Cancer = out of control cell division Hyperplasia = increased number of cell divisions –benign tumor does not metatasize or spread –malignant---spreads due to cells that detach from tumor and enter blood or lymph Causes -- carcinogens, x-rays, viruses –every cell has genes that regulate growth & development –mutation in those genes due to radiation or chemical agents causes excess production of growth factors Carcinogenesis –multistep process that takes years and many different mutations that need to occur THE END