Cellular Physiology 2024-25 Patho Schieler PDF

NUR 8901-001 Advanced Human Pathophysiology Katlyn Schieler DNP, CRNA 1  Define the following: Pathology Pathogenesis Etiology Idiopathic Iatrogenic Nosocomial Prognosis Acute Chronic sequelae 2 Cells and Tissues : Outl...

NUR 8901-001 Advanced Human Pathophysiology Katlyn Schieler DNP, CRNA 1  Define the following: Pathology Pathogenesis Etiology Idiopathic Iatrogenic Nosocomial Prognosis Acute Chronic sequelae 2 Cells and Tissues : Outline Prokarytes vs Eukaryotes Cellular structure and function Cellular communication Cellular metabolism Membrane transport Cellular reproduction Tissues Cellular adaptation Cellular Injury Cellular Death Aging 3  prokaryote eukaryote Examples: cyanobacteria, bacteria animals, plants, single- archae cell animals (fungi, most algae) Organelles: none membrane-bound intracellular compartments Nucleus: not encased by well-defined membrane Genetic info: single circular several chromosomes chromosomes 4  What Viruses are not living organisms, can’t reproduce on their own about Replication depends on ability to infect a host cell Basic structure Viruses?? Contain a core DNA or RNA surrounded by a protein shell Highly specific to a particular type of cell Transmission one infected individual to another 5  6 Virus life cycle Viruses aren’t made of cells Can’t reproduce independently Multiply by infecting living/host cells Don’t metabolize materials Don’t maintain homeostasis They do pass on genetic information 7 8 Common viruses 9 10 11 Differentiating viral v. bacterial infection Viral infection disseminated throughout the system (ex: URTI/ LRTI) may affect multiple systems Fever is usually HIGH at onset and settles by D3-4 Bacteria infection Localized to one part of the system (acute tonsillitis does not present with a runny nose or chest symptoms) Fever is generally moderate at the onset and peaks by D3-4 12 13 14 15  Cellular Functions: 1.Movement a. muscle cells generate force 2.Conductivity a. wave of excitation in response to a stimulus 3.Metabolic absorption a. take in and use nutrients from surroundings 4.Secretion a. make new substances 5.Excretion 6.Respiration 7.Reproduction 8.Communication 16  Structure and Function of Cell: Nucleus Organelles Plasma Receptors * regulates cellular Four categories of membranes *define boundaries *recognize and bind activity function ligands * “organs of the cell” 1 7 18 19 20  Organelles 1. Nucleus – is the largest membrane-bound organelle that controls activity of the cell  Contains DNA, RNA and DNA-binding proteins.  Primary job is cell-division and control of genetic information.  Histones regulate activity  Fold into chromosomes  RNA: genetic info is transcribed into RNA and it directs cellular activity in the cytoplasm. Types of RNA: 1. messenger 2. transport 3. ribosomal 21 22 Organelles cont’d 2) Ribosomes and 3) Endoplasmic Reticulum 23 24 Which of the following is a protein? Actin and myosin Hemoglobin Thrombin Insulin The insulin cell membrane receptor Antibodies Na+ and K+ channels Histamine and Bradykinin Enzymes Nicotine and muscarinic receptors 25 2 6  Protein Types Fibrous: – Muscle, tendons, connective tissue, bone Ex: actin & myosin- cardiac contractile cells collagen- skin and connective tissue structure dystrophin – skeletal muscle contractile elastin & keratin – structural 27  Protein types Globular- – More water soluble – Function to transport, catalyze and regulate Ex: albumin, Fibrin, thrombin Factor VIII, XIII, VonWillebrand Factor gamma globulin, hemoglobin, IgA, IgD, IgE, IgG, IgM, myoglobin, 28  Protein types Membrane – relaying signals, allow cells to interact, transport molecules Ex: Receptors estrogen receptor glucose transporter muscarinic and nicotinic Ach receptor, transferases 29 Membrane receptors Enzymes Insulin Nicotinic – sympathetic , motor neurons (skeletal muscle contraction) Muscarinic - parasympathetic Antibodies Na+ and K+ channels Compliment system 30 4. Golgi Complex- *a refining area and directs traffic in the cell. 31 The above drawing shows an actual interface between the ER and the Golgi complex. 32  Organelles (con’t.) 5. Lysosomes- *contain digestive enzymes that work in the intracellular digestive system for normal digestion of cellular nutrients and debris. 33  Organelles (con’t.) 5. Peroxisomes- *(microbodies) contain enzymes that use O2 to remove Hydrogen during oxidative reactions. 34  Organelles (con’t.) 6. Mitochondria- *generate most of the cell’s ATP. 35 7. Vaults- cytoplasmic ribonucleoproteins that are octagonal shaped to carry RNA from the nucleus to ribosomes. 8. Cytosol- semiliquid portion of cell. Functions to synthesize ribosomal proteins, store CHO, fats and secretory vesicles, and where intermediate metabolism occurs. 36 9. Cytoskeleton- A. maintains the cell’s shape and internal organization. Allows for external movements (cilia or flagella). B. internal protein filaments: A. microtubules- add strength to cell B. actin filaments- occur in bundles for cellular locomotion and shape. 37 Plasma Membrane s Control the composition of the space (cell). Role in cell-to-cell recognition, allow entry to cell (or not). Functions: 1. Transport molecules in and out of cell 2. catalyze membrane rxns 3. receive messages- act as receptors 4. create structural linkages between the outside and 38 inside. Cell membrane 39 Note the hydrophobic and hydrophilic regions 40  Cellular Receptors Protein molecules found: *cell membrane * in the cytoplasm * in the nucleus *Recognize and bind with specific molecules (called ligands) ligand = molecule or substance. Ex. bicarb types: 1. channel-linked: rapid signaling between electrically excitable cells. 2. catalytic: function directly as enzymes once activated 3. G-protein linked: indirectly activate 41 enzyme or ion channel 42 43  Involved in information transfer (signal transduction) from G outside cell to inside cell Protein Vision, taste, smell, sympath Channel Responsible for every aspect of etic, parasym pathetic, Recepto metaboli human biology sm, immune regulatio rs n, reproduct ion (GPCRs) *45% of all pharmaceuticals known to target GPCRs* 44 45 4 6 Cell-to-cell adhesions- how are cells held together to form tissues and organs? 47 48  Connective tissues 1. Collagen- fibers that provide tensile strength (resists being pulled apart) 2. Elastin- rubber like protein--- stretches 3. Fibronectin- promotes cell- adhesion and anchorage (a lack is found with certain cancers- lets the cells travel.) 49 Cellular communication Signal transduction First messenger- chemical that stimulates membrane receptor to cause an opening or closing of a channel OR the transfer of a signal to an intracellular messenger [EXTRAcellular] Second messenger- internal messenger that stimulates a cascade of biochemical events. [INTRAcellular] 50 51  Extra cellular Messengers and Channel Regulation occurs by binding of a ligand, changes in electric current in plasma membrane or stretching or chemical deformation of the channel. Cellular Communication 5 2 Cellular Communication (con’t.) 3. Second Messengers types-  cyclic AMP- ligand binds cell- membrane receptor and activates adenylyl cyclase via a G-protein ( GTP or GDP)  Ca+ ligand binds cell- membrane receptor and activates enzyme phospholipase C (via a G-protein) which mobilizes the Ca stored within organelles.  Ca activates calmodulin that 53 54 55 56 57 58 59 60 61  Cellular metabolism 1. Maintaining cellular functions Energy using: anabolism Energy-releasing: catabolism 2. Role of ATP (adenosine triphosphate)- form of energy stored and transferred by cells and when glucose is broken down to form H2O and CO2 3. Food and production of cellular energy- digestion = catabolism of fats, proteins and CHOs 62  Phases of catabolism (digestion) 63 64 The net yield of ATP in glycolysis is 2 for each glucose molecule (2 are used but 4 are produced). 65  Glycolysis= glyco(sugar) Goal: break glucose down to form two pyruvates Who: all life on earth performs glyclolysis Where: the cytoplasm Glycolysis produces 4 ATP's and 2 NADH, but uses 2 ATP's in the process for a net of 2 ATP and 2 NADH NOTE: this process does not require O2 and does not yield much energy 66 67  Kreb’s cycle 68 Citric acid cycle = kreb’s cycle A series of chemical reactions used by all aerobic organisms to generate energy through the oxidization of acetate derived from carbohydrates, fats and proteins into carbon dioxide. Oxidative Phosphorylation: the process of releasing ATP by oxidating the byproducts of the citric acid cycle (NAD – a coenzyme and succinate 69  3 phases of digestion (catabolism of nutrients) First: digestion of large macromolecules to simple subunits proteins- amino acids CHO- simple sugars fats- fatty acids Phase 1: Digestion Occur outside cell within intestines or within cell activated by enzymes Phase 2: Glycolysis and oxidation Glycolysis-splitting of 1 glucose into 2 pyruvate ATP NADH produced through oxidation Phase 3: citric acid cycle Most ATP generated in this phase Begins with citric acid cycle ends with oxidative phosphorylation 70  All organisms produce ATP by releasing energy stored in glucose and other sugars. Aerobic respiration: chemical reaction: C6H12O6 + 6O2 >> 6CO2 + 6H2O This reaction takes place over the course of three major reaction pathways Glycolysis The Krebs Cycle Electron Transport Phosphorylation (chemiosmosis) 71  Glycolysis: 2 ATP Net Engergy Productio Krebs Cycle: 2 ATP n from Aerobic Electron Transport Phosphorylation: 32 Respirati ATP on Net Energy Production: 36 ATP! 72 73 74 Anaerobic metabolism Goal: to reduce pyruvate, thus generating NAD+ Where: the cytoplasm Why: in the absence of oxygen, it is the only way to generate N AD+ (the co-enz needed for phosporylation) Alcohol Fermentation - occurs in yeasts in many bacteria 75  Lactic acid fermentation: anaeorbic – The product of Lactic Acid fermentation, lactic acid, is toxic to mammals – This is the "burn" felt when undergoing strenuous activity 76 77 Anaerobic metabolism The only goal of fermentation reactions is to convert NADH to NAD+ (to use in glycolysis). No energy is gained anaerobic respiration = 2 ATP's produced (from glycolysis) aerobic respiration - 36 ATP's produced (from glycolysis, Krebs cycle, and Oxidative Phosphorylation) an oxygen-rich atmosphere 78 facilitates the aerobic respiration 79 Phases of catabolism (digestion) 80 8 1 ATP Created from the chemical energy contained within organic molecules Used in synthesis of organic molecules, muscle contraction, and active transport 82  Deficit of ATP Na build-up inside the cell Cell membrane permeability increases Intracellular enzyme leakage Cell death Example: – in MI: no cell ATP in cardiac cells CPK leaks into ECF 83  Deficit of O2 Glycolysis is Glycolysis occurs in anaerobic cytoplasm 84 If O2 is available, the citric acid and If no O2, glycolysis is phosphorylation only option for ATP steps continue to (energy production) product much more phase 2 ATP (phase 3) Membrane Transport: the intake of nutrients and the export of metabolites Movement of water and solutes Transport by Vesicle Formation Movement of Electrical Impulses: Membrane Potentials 85 Movement of water and solutes Passive transport: water and small electrically uncharged particles easily move through pores in the lipid bilayer of the plasma membrane. Driven by osmosis, diffusion and hydrostatic pressure No energy expended 86  Solutes: Dissolved substances Movement through membranes dependent on: size, solubility, electrical properties, concentration 1. Electrolytes- dissociate (separate) into ions in a solution Ions- atoms cations- positively charged K+ is intracellular, Na+ is extracellular anions-negatively charged 2. Non-electrolytes 87  Diffusion Depends on concentration gradient The rate of diffusion is influenced by the size of the solute and its lipid solubility. O2, CO2 and steroid hormones are lipophilic (hydrophobic) and diffuse quickly – nonpolar 88 Diffusion: The movement of molecules from a region of higher concentrati on to a region of 89  Filtration Movement of water and solutes through a membrane because of a greater pushing force on one side of the membrane. Hydrostatic pressure: mechanical force of water pushing against cellular membranes. – ex. blood pressure In capillary bed hydrostatic pressure 25-30 mmHg – balanced by osmotic pressure 90 9 1 92  Osmosis The movement of water down a concentration gradient Osmolality- refers to the concentration of molecules per weight of water. Normal 280-295 mOsm/kg Osmolarity refers to the concentration of molecules per volume of water. Plasma has many particles so less of the plasma weight is water. Osmolality is the preferred measure of osmotic activity in people. 93  Osmosis The movement of water across a semi permeable membrane. Osmosis is the movement of water (red dots) through a semipermeable membrane to a higher concentration of solutes (blue dots). 94  Oncotic pressure = colloid osmotic pressure overall osmotic effect of colloids, such as plasma proteins. proteins have a negative charge proteins are large and non-diffusable Therefore, anions are driven out of the cell and cations are attracted. anion= ?? cation= ?? what pathophysiology does this explain?? 95 Tonicity = osmolality Isotonic solution- same concentration of particles as ICF or ECF ex. ?? Hypotonic solution- more dilute (less particles) then bldy fluids. ex. ?? Hypertonic solution- less dilute (more particles) then body fluids. ex. ?? 96  Isotonic solution A solution that has the same salt concentration as the normal cells of the body and the blood. When a cell is placed in an isotonic solution, the water diffuses into and out of the cell at the same rate. The fluid that surrounds the body cells is isotonic. 97  Hypotonic solution contains a solution with a lower salt concentration than in normal cells When a cell is placed in a hypotonic solution, the water diffuses into the cell, causing the cell to swell and possibly explode. 98  Hypertonic solution contains a high concentration of solute in relation to the solution within the cell (e.g. the cell's cytoplasm). When a cell is placed in a hypertonic solution, the water diffuses out of the cell, causing the cell to 99 shrivel up. 100  Membrane Transport: the intake of nutrients and the export of metabolites 1. Movement of water and solutes 2. Transport by Vesicle Formation 3. Movement of Electrical Impulses: Membrane Potentials 101  Diffusion Filtration- based on solution / solute concentration (osmosis and osmolality) Mediated transport Passive Active 102 Mediated transport: 1. Passive or Facilitated diffusion- This process does not require ATP but does require cell membrane proteins which are called carrier proteins to carry the molecules across the cell membrane from an area of higher concentration to an area of lower concentration. 103 Active Transport Active Transport requires the cell to use energy, usually in the form of ATP. Active Transport creates a charge gradient in the cell membrane. For example in the mitochondrion, hydrogen ion pumps pump hydrogen ions into the intermembrane space of the organelle as part of making ATP. 104  Protein’s function in transport across a membrane: 1. Transport protein- Binds with a specific solute molecule across the lipid bilayer Each transport protein has a receptor for a specific solute. When all the receptor sites are occupied by a solute molecule, the rate of transport is maximal. Competetive Inhibitor- occupy the same receptor site but do not permit transport of the solute across the lipid membrane. Ex.: beta receptor antagonist (beta 105 blocker) Protein’s function in transport across a membrane: Channel Protein- Creates a “pore” through which specific ions can pass. Ion channels are responsible for the electrical excitability of nerve and muscle cells and play a critical role in membrane potential. 106  Membrane Transport: the intake of nutrients and the export of metabolites 1. Movement of water and solutes 2. Transport by Vesicle Formation 3. Movement of Electrical Impulses: Membrane Potentials 107 Transport by Vesicle Formation- requires the formation of membrane-bound containers. Endocytosis- a section of the plasma membrane forms a pouch that engulfs a macromolecule. 1. pinocytosis 2. phagocytosis Exocytosis- secretion of macromolecules via intracellular vesicles at the cell surface. functions: 1. Replacement of portions of the plasma membrane that have been removed by endocytosis 2. Release of molecules synthesizes by the cells (like insulin) 108  Membrane Transport: the intake of nutrients and the export of metabolites 1. Movement of water and solutes 2. Transport by Vesicle Formation 3. Movement of Electrical Impulses: Membrane Potentials 109  Membrane potentials Movement of electrical impulses T/ F all cells are electrically polarized. Which is more negative? The inside or the outside? Resting membrane potential: ?? Ion in the cell (ICF): Ion outside the cell (ECF): Na+ / K+ pump: which ion which direction? 110  Nerve and muscle cells are excitable and can change their RMP in response to electrochemical stimuli. Changes in RMP convey messages from cell to cell. Action potential: nerve or muscle receives a stimulus that rapidly changes the RMP 111 112 Na/K pump maintains RMP 113 114  Stages of an action potential: Resting: cell at rest, sodium-potassium pump maintaining resting potential (-70 mV). Lots of sodium outside, lots of potassium inside. Ion channels closed so the established ion gradient won't leak. Depolarization: sodium channels open, positive sodium rushes inside, membrane potential shoots up to +30 mV. Lots of sodium inside, lots of potassium inside. Repolarization: potassium channels open, sodium channels close, positive potassium rushes outside, membrane potential drops back down. Lots of sodium inside, lots of potassium outside (opposite of the resting state) Hyperpolarization: potassium channels doesn't close fast enough, so the membrane potential actually drops below the resting potential for a bit. Refractory period: the sodium-potassium pump works to re- establish the original resting state (more potassium inside, sodium outside). Until this is done, the neuron can't generate another action potential. Absolute refractory period = from depolarization to the cell having re-established the original resting state. Relative 115 refractory period = After hyperpolarization till resting state re-  summary RMP Depolarization Repolarization Return to resting potential 116  117 Phases of mitosis and cytokinesis Cellular Reproduc Rates of tion cellular division the cell cycle Growth factors Basic terms: Meosis- reproduction through gametes (sperm and egg) Mitosis- nuclear cell division Cytokinesis- cytoplasmic division 118  Rates of cellular division: very varied Nerves, lens of the eye Epithelial cells (intestine, The difference in and muscle cells lose the skin, lung) divide replication speed is the ability to replicate and continuously and rapidly time spent in G1- the gap divide (1 layer cell shape Squamous- flat and thin Cuboidal-appear square Columnar- rectangular 121  Simple sqaumous Simple cuboidal epithelium epithelium Simple columnar epithelium Ciliated columnar122 epithelium Glandular epithelium 123 Connective Tissue The framework on which epithelial cells cluster to form organs. binding organs and tissues together Functions: supporting tissues storage sites for nutrients Produce fibers Collagenous (white) Elastic (yellow)- long fibers that (fibroblasts)- strong allow stretching Reticular- short, branching that and elastic provide structure 124 Types of Cartilage. 125 Structure of long bone with enlargement of a section of compact bone. 12 6 Composition of Blood 127 Muscle Tissue Myocytes- long, thin, highly contractile cells Cardiac smooth skeletal 128 129  Neural tissue Neurons that receive and transmit electrical impulses very rapidly Synapses- where neurons contact one another Neuron- contain cell body, single axon and > 1 dendrite 130 131  Maximal Life span of humans??? http://www.worldlifeexpectancy.co m/world-life-expectancy-map Life Expectancy- avg # of years of life remaining at a given age. Insulin & insulin-like Growth factor-1 (IGF-1) signaling pathway is an endocrine regulator of aging. Necessary for homeostasis, growth and survival 132 Aging process- many theories: Aging process- many theories: 1. Cellular damage 2. Molecular disorder 3. Degenerative extracellular changes  Cellular aging Atrophy – Physiologic or pathologic Compensatory mechanisms: hypertrophy hyperplasia Altered: receptor function, nutrient pathways, secretion of cellular products, neuroendocrine control mechanisms 134 Cellular aging Decreased capacity for DNA repair When the mitochondrial DNA can not be repaired, the cell can be deprived of ATP. 135  Tissue and systemic aging Every physiologic process functions less efficiently with age Progressive stiffness: arterial, pulmonary, musculoskeletal system Endocrine: thymus atrophy- occurs at puberty, decreased immune response to T-dependent antigens Reproductive: loses ova in women and spermatogenesis in men GI- decreased gastric emptying (increased time) Neuromuscular: sarcopenia Integumentary: loss of elasticity and wrinkling 136  Total body Changes seen with Aging: Decreased bond density and mass: Decreased stature (height) Widening of the pelvis osteoporosis and osteoarthritis Tissue atrophy: Decreased circumference of neck, thighs and arms Lengthening of the nose and ears Body Composition: decreased free-fat mass, decreased weight 137 decreased total body water  Frailty Wasting syndrome of aging Prone to falls, functional decline, disease and death Decreased protein synthesis, sarcopenia (decreased lean body mass), neuroendocrine and muscular decline, immune dysfunction Cognitive impairment, anemia, ostesopenia 138  Gender differences in Frailty Men: higher muscle mass testosterone and GH support muscle mass alterations in immune fxn and immune responsiveness to sex steroids make men more vulnerable to sepsis Women: cortisol is more dysregulated in older women lower activity levels and caloric intake may increase susceptibility for139  LAST SLIDE!!!!  Somatic Death Death of the entire person Postmortem changes: cessation of respiration and circulation skin pallor temperature drop 1-1.5 deg F/hour (algor mortis) pupil dilation (decreased BP to retina) blood pooling- liver mortis rigor mortis- within 6 hrs, acids accumulate small muscles affected first putrefaction- decay after 24-48 hours 140