Basic Understanding of Pathophysiology & Cellular Mechanisms and Regulation PDF

Basic Understanding of Pathophysiology & Cellular Mechanisms and Regulation Course content provided by Dr. Rae Marceau, modified by Leanne Boudreau Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reser...

Basic Understanding of Pathophysiology & Cellular Mechanisms and Regulation Course content provided by Dr. Rae Marceau, modified by Leanne Boudreau Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. Pathophysiology Terms Pathophysiology: the study of the underlying changes in body physiology that result from disease or injury Etiology: the study of the cause of disease Idiopathic: diseases that have no identifiable cause Acute Disease: sudden appearance of signs and symptoms that only last a short time Chronic Disease: slowly develops and signs and symptoms last for a long time (potentially a lifetime) Remissions: periods where symptoms disappear or diminish significantly Exacerbations: periods with the symptoms become worse or more severe Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. Pathophysiology Terms Clinical Manifestations: signs and symptoms or evidence of the disease Signs: objective alterations that can be observed or measured Symptoms: subjective experiences reported by the person with disease Syndrome: a group of symptoms that occur together, and may be caused by several interrelated problems Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. What is a cell? The smallest unit of life and the building block of all living organisms What are the 2 Types of Cells? Prokaryotic- single-cell organisms; bacterias and some algae Eukaryotic- makeup more complex organisms, have a membrane bound nucleus Cell Structure Review https://www.youtube.com/watch?v=HBvfBB_oSTc Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. Prokaryotes ➔ No distinct nucleus (single, circular chromosome) ➔ No organelles ➔ Cyanobacteria, bacteria, and rickettsiae Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. Eukaryotes ➔ Complex cellular organization ➔ Membrane-bound organelles ➔ Well-defined nucleus with several chromosomes ➔ Higher animals, plants, fungi, and protozoa Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. Cell Structure ➔ Plasma membrane: outer membrane ➔ Cytoplasm: fluid “filling”, the cell would shrink without this ➔ Organelles: “organs” of the cell ◆ Nucleus ◆ Nucleolus ◆ Lysosome ◆ Mitochondria ◆ Ribosomes ◆ Endoplasmic Reticulum ◆ Golgi Complex Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. Eukaryotic Cell Structure Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. 8 Organelles: the Nucleus Nucleus – DNA – nuclear envelope ○ Largest membrane-bound organelle Replicates - Cell division Genetic information – chromosomes Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. Organelles: Ribosomes Ribosomes ○ RNA protein complexes ○ Synthesized in nucleolus ○ Sites for cellular protein synthesis ○ Important for cell replication Organelles: Endoplasmic Reticulum Endoplasmic reticulum ○ Cisternae ○ Synthesis and transport of protein and lipids Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. Organelles: Golgi Complex Golgi complex ○ Processing and packaging of proteins ○ Secretory vesicles (release protein packages to neighbouring cells if necessary) Organelles: Lysosomes Lysosomes ○ Originate from the Golgi ○ Contain enzymes for digestion- digestive organ cell ○ Cellular injury causes enzyme release that leads to cellular self-destruction, and then autodigestion of the cell Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. Organelles: Mitochondria Mitochondria ○ Cellular energy metabolism AKA “the power house of the cell” ATP generation ○ Has role in: Osmotic regulation, pH control, calcium homeostasis & cell signalling Organelles: Peroxisomes Perioxisomes ○ participates in oxidation. Oxidation in organelles – this is why we take antioxidants - to try and and bind up the extra oxidative enzymes in the body. ○ Contain oxidative enzymes which break cellular waste down into harmless products Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. Organelles: Cytoskeleton Cytoskeleton ○ “Bones and muscles” of cell shape ○ Composed of protein filaments ○ Forms cell extensions Organelles: Vaults ⬤ Vaults Cytoplasmic ribonucleoproteins, shaped like octagonal barrels Cellular trucks Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. Biochemical Activity in Eukaryotic Cells ➔ Protein synthesis ➔ Enzyme content ➔ Transport across outer cell membrane Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. The Cell Membrane Plasma Membrane AKA Phospholipid Bilayer ○ Allows selective passage of certain substances into and out of cells Phospolipid Bilayer Composition ○ Hydrophylic head & hydrophobic tails Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. Lipids & Carbohydrates and the Cell Lipids ○ Function as essential structural components of membranes, as signalling molecules, as chemical identifiers of specific membranes and as energy storage molecules. Carbohydrates ○ Supply energy to all the cells in the body Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. Functions of Cell Membrane Cell-to-cell Recognition ○ how the body knows the difference between normal and cancerous cells Membrane Potential ○ via potassium and sodium channels ○ membrane potential; electrical energy Movement of Molecules ○ Endocytosis – bringing things into the cell – liquids and molecules ○ Exocytosis - cellular excretion waste – or secretion of hormones ○ Cell Receptor – on the surface of the cell. Can shut on and off cell permeability. ○ Cell Adhesion – one cell hooks up with another cell to hold an organ together. Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. Proteins in the Cell Membrane ⬤ Major workhorses of the cell Functions Receptors Surface markers Transport Cell adhesion molecules channels/carriers (CAMs) Enzymes Catalysts Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. Proteins: Cell Surface Receptor ⬤ Cellular receptors are proteins either inside a cell or on its surface, which receive a signal. ⬤ Ligands Bind with cellular receptors to activate or inhibit the receptor’s associated signaling or biochemical pathway ⬤ Plasma membrane receptors Determine response to binding A cell receptor is a protein molecule to which substances like hormones, drugs, and antigens can bind Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. Cell-to-Cell Adhesion Represents the mechanism behind how cells interact with each other, based on molecule reactions at the surface of both cells. *Cell adhesion is a dynamic process that is particularly evident where nonadhesive cells rapidly become adhesive, for example, leukocytes in inflammation and platelets in blood clotting* Held together by: Extracellular membrane Cell adhesion molecules (protein) Specialized cell junctions Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. Cell-to-Cell Adhesion: Extracellular Membrane Extracellular matrix—secreted by cell itself Fibrous proteins in gel substance Produced by fibroblasts Diffusion of water, nutrients Composed of: Collagen Elastin Fibronectin Regulates cell growth, movement, and differentiation Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. Cell-to-Cell Adhesion: Cell Junctions ⬤ Cell junctions Symmetrical Desmosomes – hold our cells together – like a belt Unite cells Tight junctions – desmosomes gluing cells together Barriers Gap junctions – cell signaling Communication Asymmetrical Hemidesmosomes -Hemidesmosomes are very small stud-like structures found in keratinocytes of the epidermis of skin that attach to the extracellular matrix. ⬤ Gating Enables uninjured cells to protect themselves from injured neighbours Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. Cellular Functions 1. Movement - muscles 2. Conductivity - nerve cells, heart cells, muscle cells 3. Metabolic absorption - absorb nutrients 4. Secretion - hormones 5. Excretion - use nutrients and excrete them 6. Respiration - process of using O2 7. Reproduction - replication 8. Communication - between cells *Specialized through differentiation or maturation* Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. Cellular Functions: Communication ⬤ Communication with other cells Think of the heart. Heart generates a membrane potential in one cell which communications and generates an electrical impulse. ⬤ Sensing signals External cells: temperature regulation, skins cells Internal cells: change in pH causes cells to adapt and respond ⬤ Chemical signaling Paracrine – hormones have effect on target cells next to it. Autocrine – cell secretes hormone to target self Hormonal – cell releases hormone goes through bloodstream. Neurohormonal – neurons in the brain secret hormone into the bloodstream – fight or flight Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. Cellular Cemical Signaling Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. 25 Signal Transduction ⬤ We are moving communication from cell to cell in the body. ⬤ Cells communicate via receptor protein Signals molecules to activate protein kinases Instructs cells to grow and reproduce, die, survive, or differentiate Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. 26 Cellular Communication Gone Wrong 1. Losing the Signal The food that you eat is broken down into sugar, which enters the bloodstream. Normally, cells in the pancreas release a signal, called insulin, that tells your liver, muscle and fat cells to store this sugar for later use. In type I diabetes, the pancreatic cells that produce insulin are lost. Consequently, the insulin signal is also lost. As a result, sugar accumulates to toxic levels in the blood. Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. 27 Cellular Communication Gone Wrong 2. Signal Doesn’t Reach it’s Target Multiple sclerosis is a disease in which the protective wrappings around nerve cells in the brain and spinal cord are destroyed. The affected nerve cells can no longer transmit signals from one area of the brain to another. The nerve damage caused by multiple sclerosis leads to many problems, including muscle weakness, blurred or double vision, difficulty with balance, uncontrolled movements, and depression. Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. 28 Cellular Communication Gone Wrong 3. When the Target Ignores the Signal Type I and type II diabetes have very similar symptoms, but they have different causes. While people who have type I diabetes are unable to produce the insulin signal, those with type II diabetes do produce insulin. However, the cells of type II diabetics have lost the ability to respond to insulin. The end result is the same: blood sugar levels become dangerously high. Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. 29 Cellular Communication Gone Wrong 4. Multiple Breakdowns Cell growth and division is such an important process that it is under tight control with many checks and balances. But even so, cell communication can break down. The result is uncontrolled cell growth, often leading to cancer. Cancer can occur in many ways, but it always requires multiple signaling breakdowns. Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. 30 Cellular Communication Gone Wrong 5. Too Much Signal A stroke occurs when a blockage forms in a blood vessel, cutting off blood flow to part of the brain. The immediate result is the death of nearby brain cells. But the most catastrophic event comes later, when the dying cells release large amounts of the signaling molecule glutamate. Low concentrations of glutamate control many actions in the brain, but at high concentrations it is toxic to cells. Through a process called excitotoxicity, glutamate spreads through the brain and kills cells that were not affected by the blockage, often leading to widespread brain damage. Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. 31 Cellular Fuction: Metabolism ⬤ Metabolism Chemical tasks of maintaining essential cellular functions Anabolism= Energy using Catabolism= Energy releasing ⬤ Digestion Extracellular breakdown of proteins, fats, polysaccharides into subunits ⬤ Glycolysis Intracellular breakdown of subunits to pyruvate, then to acetyl CoA Anaerobic Limited ATP produced Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. 32 Cellular Energy Definitions ⬤ Adenosine Triphosphate (ATP): fuel for cell survival ⬤ Citric Acid (Krebs Cycle): ATP produced via oxidative phosphorylation if oxygen present – produces energy from metabolism from fats, CHO’s and lipids ⬤ Anaerobic Glycolysis: if oxygen is not available, glucose is converted to pyruvic acid (pyruvate) in cytoplasm with production of two ATP molecules, which is insufficient for energy needs; pyruvate then converted to lactic acid *reverses itself once O2 available again* ⬤ Oxidative phosphorylation: occurs in the mitochondria, mechanism producing energy from fats, CHO, proteins Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. 33 Cell Membrane Transport ⬤ Cellular intake and output Cells continually take in nutrients, fluids, and chemical messengers from the extracellular environment and expel metabolites, or the products of metabolism, and end products of lysosomal digestion. Transporters allow movement of ions that fit the unique binding sites on the protein. Channels allow ions and selective molecules to diffuse across the membrane. Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. 34 Cell Membrane Transport ⬤ Passive transport Molecules move easily from region of high concentration to region of low concentration Requires no energy Driven by osmosis, hydrostatic pressure, and diffusion ⬤ Active transport Flows “uphill” Requires energy Transporter pumps Endocytosis = taking into cell Exocytosis = expelling from cell Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. 35 Cell Membrane Transport ⬤ Electrolytes Account for ~95% of solutes in body fluids Electrically charged Needs to be balanced at all times – take in too much (ie take too much energy drinks) – body will excrete it. Cations – positively charged Anions - negatively Measured in milliequivalents per litre (mEq/L) or millimoles per litre (mmol/L) Different charges – some have one charge monovalent sodium. Calcium is divalent – two charges. Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. 36 Cell Membrane Transport ⬤ Diffusion –passive transport – no energy or ATP needed Movement of solutes from area of greater concentration to area of lesser concentration Rate of diffusion influenced by difference of electrical potential across the membrane Also influenced by size of molecules and lipid solubility think of a coffee filter and water (and coffee) running through the filter Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. 37 Cell Membrane Transport ⬤ Filtration –Movement of water and solutes through a membrane because of greater force on one side than on the other Hydrostatic pressure – the pressure in the blood vessel the higher the pressure the more fluid that gets moved out. Eg. Blood pressure Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. 38 Cell Membrane Transport ⬤ Osmosis Movement of water down a concentration gradient Membrane must be more permeable to water than solutes Concentration of solutes on one side greater than the other Controls the distribution of water between body compartments Osmotic pressure Oncotic pressure or colloid osmotic pressure Tonicity – osmolarity and osmolality Fluid is going to move from less electrolyte to more electrolyte Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. 39 Cell Membrane Transport ⬤ Osmolality Measures the number of milliosmoles per kilogram (mOsm/kg) of water Concentration of molecules per weight of water To balance the concentration of water ⬤ Osmolarity Measures the number of milliosmoles per litre of solution Concentration of molecules per volume of solution Think of concentration of water when you see these two terms Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. 40 Cell Membrane Failures ⬤ Aging Process ⬤ Cardiac muscle contraction and acute injury (such as ischaemia–reperfusion injury); ⬤ Neuronal Diseases – Alzheimers ⬤ Lack of O2 see above ischemia ⬤ Viruses and Bacteria ⬤ Medications that we ingest Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. 41 Passive Mediated Transport and Active Transport ⬤ Passive – no energy or ATP – having specific channels to allow the electrolytes to pass into the cell. Ie. protein transporter ⬤ Active is the Transport system for Na+ and K+ ⬤ Uses direct energy of ATP ATPase Process leads to electrical potential Sodium potassium pump in and out of the cell Endocytosis – vesicle formation Exocytosis moving substances out of the cell. Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. 42 Transport by Vesicle Formation ⬤ Transport of macromolecules Endocytosis Vesicle formed and moves into cell Pinocytosis—ingestion of fluids Phagocytosis—ingestion of large particles Waste products of endocytosis are excreted Exocytosis Replaces plasma membrane removed by endocytosis Releases synthesized molecules into extracellular matrix Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. 43 Membrane Potential ⬤ Resting membrane potential is what is going to allow the cell to be able to create electrical energy. More charge on one side of the membrane than the other. Making the cell capable of electrical discharge ⬤ Think of the heart cells and an ECG ⬤ Action potential Depolarization – more energy in the cell – heart muscle contracts. It can’t contract all day long. It needs to contract. Reaches the threshold. Now it needs to repolarize. Sodium potassium is going to pump sodium back in and potassium back out. Threshold potential Hyperpolarized versus hypopolarized Repolarization Refractory period Absolute and relative Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. 44 Sodium–Potassium Pump and Propagation of an Action Potential Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. 45 The Cell Cycle ⬤ The cell cycle is an ordered series of events involving cell growth and cell division that produces two new daughter cells. Cells on the path to cell division proceed through a series of precisely timed and carefully regulated stages of growth, DNA replication, and division that produce two genetically identical cells. ⬤ The cell cycle has two major phases: interphase and the mitotic phase. During interphase, the cell grows and DNA is replicated. During the mitotic phase, the replicated DNA and cytoplasmic contents are separated and the cell divides. Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. 46 The Cell Cycle – Cell Growth and Division ⬤ Mitosis versus cytokinesis ⬤ Both are part of cell division ⬤ Mitosis is based on the need for a cell to grow and regenerate. Mitosis lies behind the propagation and continuation of all living forms. ⬤ Mitosis is a process by which the duplicated genome in a cell is separated into halves that are identical in nature. ⬤ Cytokinesis is the process where the cytoplasm of the cell divides to form two 'daughter’ ⬤ Cytokinesis ensures that the chromosome numbers are maintained in cells. Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. 47 Four Phases of the Cell Cycle https://www.youtube.com/watch?v=e6N9_RhD10Q Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. 48 Four Phases of the Cell Cycle ⬤ Gap 1 or G1 phase, where the cell grows in size, and checks that everything is OK for it to divide. ⬤ Synthesis or the S phase, where the cell copies its DNA. ⬤ Gap 2 or G2 phase, where the cells check that all its DNA has been correctly copied. ⬤ Mitosis or M phase, where the cell finally divides in two. Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. 49 Cells Stop Growing ⬤ Normal growth and healing is well ordered and precise. The cells know when: there are enough new cells to heal a cut a structure such as a finger is fully grown ⬤ Cells send chemical messages to each other so that they stop growing and dividing when growth or healing is complete. The diagram below shows this happening. Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. 50 Influences on the Cell Cycle ⬤ Cellular division rates depend on: Protein growth factors Genetic factors - mutations Epigenetic factor Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. 51 Tissue Formation ⬤ Intercellular recognition and communication, adhesion, and memory ⬤ Specialized patterns of gene expression ⬤ Terminally differentiated cells ⬤ Stem cells ⬤ Cells, the smallest structural and functional unit in the human body, form tissues, which assemble into organs, which finally group into organ systems Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. 52 Types of Tissue ⬤ Nerve Highly specialized cells (neurons) ⬤ Epithelial Covers most of internal and external body surfaces ⬤ Connective Binds tissues and organs together Dense, elastic, connecting things together ⬤ Muscle Composed of myocytes, enables movement Smooth, striated (skeletal), cardiac Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. 53 Overview of Learning Objectives 1. Define pathophysiology 2. Explain the role of pathophysiology in the development of disease 3. Understand cellular mechanisms Copyright © 2019, Elsevier Canada, a division of Reed Elsevier Canada, Ltd. All rights reserved. 54