EHS 202 Week 1 Homeostasis 2023-2024 PDF

EHS 202 Pharmacology for EMS Week 2: Introduction to Homeostasis Objectives of this lecture: Describe the concept of homeostasis and the transport mechanisms used to maintain normal cellular function; Discuss the properties of hydrophilic and hydrophobic substances; Describ...

EHS 202 Pharmacology for EMS Week 2: Introduction to Homeostasis Objectives of this lecture: Describe the concept of homeostasis and the transport mechanisms used to maintain normal cellular function; Discuss the properties of hydrophilic and hydrophobic substances; Describe the general principles of protein synthesis and the role of proteins in the body; Describe the role and function of enzymes; Describe and give examples of positive and negative feedback mechanisms used throughout the body. 2 To effectively treat patients, the paramedic needs to understand normal & abnormal physiology. When a patient is sick or injured their normal physiological response is altered which affects the movement of drugs through the body (pharmacokinetics) and the body’s biological response to the drug (pharmacodynamics). The principles of pharmacokinetics and pharmacokinetics are discussed in next weeks lectures. 3 Homeostasis What is homeostasis????? 4 When we administer drugs to a patient, we are effectively saying that the body’s homeostatic and feedback mechanism are not functioning correctly. We are trying to exogenously (from outside the body) intervene. 5  Homeostasis Cells have specific requirements or a ‘normal range’ to maintain normal cellular function including glucose, oxygen, sodium and other salts, pH, waste products and temperature. Temperature 36.5 – 37.5 pH 7.35 - 7.45 6  Homeostasis The concept of homeostasis is simply maintaining a constant internal environment with a balance of physiological variables despite external conditions and stressors. Homeostasis is a dynamic process and no physiological processes are constant over long periods of time (temperature, pH, glucose levels). Homeostasis must be considered individually for each physiological variable and are described as being in a state of dynamic constancy. Homeostatic failure of one variable can result in a series of changes in others. Homeostasis is regulated by control systems including feedback mechanisms, reflexes, hormones, chemical messengers and biological rhythms. 7 Homeostasis Homeostasis of the individual components results in differences in concentration between the ECF and ICF for each component. Normal cellular homeostasis and equilibrium also results in an electrochemical potential difference between the ECF and ICF. Despite constant movement of ions and electrochemical potential there is a state of dynamic equilibrium. 8  Diffusion All molecules are in a constant state of movement or vibration. The greater the energy state, the greater the movement and at certain points will determine the state of the substance (solid, liquid, gas). The random thermal motion of molecules in a liquid or gas will eventually result in even distribution of that molecule within a container. Diffusion results in the movement of solute from high concentration to low concentration until uniformly distributed. The rate of diffusion is related to the magnitude of the concentration difference between two compartments. 9 Diffusion All processes in living organisms are influenced by the continuing process of diffusion including the diffusion of oxygen, carbon dioxide, salts and ions and glucose. The most complicated pathology or drug at a molecular level is normally associated with an alteration or impairment of either concentration gradients or diffusion. 10  Diffusion across a semi-permeable membrane Osmosis is the diffusion of water from low solute concentration to high solute concentration. Water is able to easily move across the semi- permeable membrane while the solute can not. An equilibrium is achieved when the competing forces of concentration (osmotic) gradient and hydrostatic pressure are balanced. 11  Diffusion across a semi-permeable membrane An additional consideration for equilibrium is the electrochemical potential concentration difference. Most molecules in solution are polar and are either positively or negatively charged. + ++ + + + + + + Electrochemical + + potential + Electrochemical potential + 12 Transport Cells maintain the electrical and chemical difference between the intra-cellular and extra-cellular environment to allow them to react and interact. In order to maintain these concentration gradients cells face a constant battle against diffusion. Some molecules pass through the cell membrane easily, others are ‘assisted’ or ‘facilitated’ while others are actively transported against their concentration gradient. 13 Equilibrium Cells maintain an osmolarity and electrochemical equilibrium between the ECF and ICF with no net movement of water or molecules (under normal resting conditions). Cells maintain a difference in ion concentration and an electrochemical charge due to the active transport of ions into and out of the cell. 14  Osmolarity Human cells have an ICF concentration of approximately 280 mOsmol/L. Penetrating solutes do not contribute to osmolality. Administration of either hypertonic or hypotonic solutions can cause cellular damage, particularly at the site of administration. RBC’s placed into an isotonic solution will neither swell or shrink. RBC’s placed into a hypotonic RBC’s placed into a hypertonic solution may swell and lyse. solution may shrivel and lyse. 15 *Osmolarity is also known as osmotic pressure – measure of solute concentration. Enzymes What are enzymes????? Write your answer down to share with the class 16  Chemical Reactions Chemical reactions involve the breaking of chemical bonds, followed by the formation of new chemical bonds to form the product molecules. Most chemical CO2 + H2O ⇋ H2CO3 ⇋ H+ + HCO3 - reactions are reversible and in a carbon water carbonic acid bicarbonate constant state of dioxide flux. The rate of chemical reactions are affected by: Reactant concentration (higher concentration: faster reaction), Activation energy (higher activation energy: slower reaction rate), Temperature (higher temperature: faster reaction rate) and The presence of a catalyst (presence of a catalyst: faster reaction rate). 17  Enzymes Enzymes are protein (predominantly) catalysts in the body that lower the activation energy required for chemical reactions to proceed. S+E Substrate Enzyme ⇋ ES Enzyme-Substrate ⇋ P+E Product Enzyme complex Enzymes are not consumed by the reaction and at the end of the reaction are able to undergo the same reaction with additional substrate molecules. Due to the nature of the enzyme binding or active site they are subject to specificity, affinity, competition and saturation. Enzymes accelerate either the forward, reverse or both forward and reverse chemical reactions but do not cause a reaction to occur that would not occur 18 otherwise Enzymes The rate of enzyme-related reactions depends on the substrate concentration (diffusion) and the concentration and activity of the enzyme. The majority of drugs, chemical messengers and mediators are metabolised or modified by enzymes. Enzyme induction, inhibition or altered kinetics are common sites of drug action. More on this in the next two weeks! 19 Proteins Some proteins are enzymes. Proteins are involved in all physiological processes. Receptors of enzymes are able to be regulated. The structure of a protein is not static and changes in structure alter the properties of the protein. 20 Proteins Protein structure can be very complicated despite the representation of a simplistic model for ease of understanding. The complex structure of proteins makes them particularly vulnerable to either temporary or permanent structural alteration by heat and extremes of pH. Permanent alteration of protein structure by acid 21 Proteins Permanent alteration of protein structure by heat 22 Hydrogen Ions, pH & Acidity 23 Hydrogen Ions, Acidity and pH The acidity of a solution refers to the free or unbound hydrogen ion concentration in solution; where the higher the hydrogen ion concentration, the greater the acidity. pH = -log [H+] Hydrogen ion concentration is expressed as a negative log; the higher the concentration of hydrogen ions, the lower the pH. Pure water has a hydrogen ion concentration of 10-7 mol/L (pH = 7.0). A solution with a hydrogen ion concentration of 10-6 mol/L (pH = 6.0) has a higher concentration of hydrogen ions and is said to be acidic. The normal value of the ICF is pH 7.0 - 7.2 while the ECF is pH 7.35 - 7.45. 24  Hydrogen Ions, Acidity and pH A hydrogen ion (H+) is a single free proton caused by the loss of an electron. Molecules that release protons in solution are referred to as acids, molecules that accept protons are referred to as bases. H2CO3 ⇋ carbonic acid H+ + HCO3- bicarbonate Proton acceptor Proton donor (Base) (Acid) The amount of separation and ionisation of a molecule in solution is indicated by whether a molecule is a weak acid (lactic acid) where only a fraction of the molecules release hydrogen, or a strong acid (HCl) where the majority of the atoms separate. 25  Hydrogen Ions, Acidity and pH Molecules including amino acids and proteins are slightly ionised and will react to the presence of other positively or negatively charged ions. If the electric charge of a molecule is altered, the way in which it interacts with other molecules (or even within the same molecule) changes leading to changes in functional characteristics. Small changes in hydrogen ion concentration can produce large changes in molecular interactions. Enzymes in particular operate within very narrow ranges of pH. 26 Hydrophobic & Hydrophillic Substances 27  Hydrophilic and Hydrophobic substances In order to dissolve in water a substance must be electrically attracted to water molecules. Molecules that have a number of polar bonds and/or ionised groups will dissolve in water and are described as being hydrophilic (water loving). Hydrophobic (water fearing) molecules are predominantly composed of carbon and hydrogen which have electrically neutral covalent bonds. 28 Feedback Mechanisms 29  Negative Feedback Substrate Enzyme A Negative feedback is where the product or response produced acts in a manner that inhibits further product or response from occurring. Intermediate 1 Enzyme B - Negative feedback prevents the compensatory response to a loss of homeostasis from continuing unabated. Intermediate 2 Enzyme C Active Product 30 Negative Feedback Insulin released to ↓ blood glucose inhibits glucagon release Negative feedback may ↑ glucose uptake occur at the molecular, ↑ glycogen synthesis cellular, organ or physiological system level of the body. Most physiological processes are controlled by negative feedback in order to maintain physiological properties Glucagon released to ↑ blood glucose and concentrations within a narrow optimum inhibits insulin release range. ↑ glucose synthesis ↑ glycogen metabolism 31  Positive Feedback Positive feedback is where the product or response produced acts in a manner that increases the rate of production or a greater response to occur. When the response amplifies the stimulus to create a greater response, the nature of positive feedback means that there is no Stimulus obvious means of stopping it. + There are few examples of positive feedback in nature with a few exceptions. Parturition is one example where uterine Physiological muscle contraction during labor initiates the Responce secretion of oxytocin which stimulates greater uterine contraction. 32 Feedback Mechanisms Medication Exam 30% Week 12 33 Drug Revision for Next Week For week 3 please study the following drugs with a focus on drug dose, presentation, indications and contraindications. Ibuprofen Paracetamol Entonox 34 References 1. ‘Vander’s Human Physiology’, 11th Edition. (Widmaier et al.) 2. ‘Rang and Dale’s Pharmacology’, 6th Edition. (Rang et al.) 3. ‘Pharmacology for Health Professionals’, 3rd Edition. (Bryant & Knights) 4. ‘Fundamentals of Pharmacology’, 5th Edition. (Bullock et al.) 5. Pollak,A.N., Elling,B., & Smith,M.( 2013). Nancy Caroline’s Emergency Care in the Streets (7th ed.) Burlington, MA : Jones and Bartlett Learning. 35