2- Cell membrane structure & transport across cell membrane.pdf

Dr. Nervana Mostafa MB BS, MD, PhD (UK) Professor of Physiology College of Medicine, KKUH, KSU [email protected]  Cell membrane structure & transport across cell membrane  objectives Describe the fluid mosaic model of membrane structure and...

Dr. Nervana Mostafa MB BS, MD, PhD (UK) Professor of Physiology College of Medicine, KKUH, KSU [email protected]  Cell membrane structure & transport across cell membrane  objectives Describe the fluid mosaic model of membrane structure and function. Define permeability and list factors influencing permeability. Identify and describe carried-mediated transport processes: Primary active transport, secondary active transport, facilitates diffusion. Differentiate between passive and active transport mechanisms and give examples on each. #Study source for this lecture: (Guyton & Hall Textbook of Medical Physiology, 13th edition) #  Cell Membrane Envelops the cell. Thin, pliable and elastic. 7 - 10 nanometer thick. Also, referred to as the plasma membrane.  Composition Lipoprotein protein 55% phospholipids 25% lipid 42% cholesterol 13% glycolipid 4% carbohydrates 3% The Cell Membrane Phospholipids Consist Of : ECF 1. Glycerol head (hydrophilic). 2. Two fatty acid ‘’tails’’ (hydrophobic). ICF The Cell Membrane Proteins Integral protein Peripheral protein  The Cell Membrane Proteins: 1. Integral proteins - Span the whole thickness of the membrane. - Proteins provide structural channels or pores. - Carrier proteins. 2. Peripheral proteins -Present in one side. - Hormone receptors. - Cell surface antigens.  The Cell Membrane Carbohydrates: - Glycoproteins (most of it) and Glycolipids. - Proteoglycans (mainly carbohydrate substance bound together by protein). - ‘’glyco’’ part is in the surface (hydrophilic). - Glycocalyx (Carbohydrate molecules protrude to the outside of the cell forming a loose carbohydrate coat “glycocalyx”.  Function Of Carbohydrates: Attaches cell to each others. Act as receptors substances (help ligend to recognize its receptor). Some enter in to immune reactions. Give most of cells overall –ve surface.  Transport across the Cell Membrane Cell membrane is selectively permeable. Through the proteins. – Water-soluble substances e.g. ions, glucose.. Directly through the lipid bilayer. – Fat-soluble substance (O2, CO2, N2, alcohol..  Types Of Membrane Transport 1- Diffusion a) simple diffusion. b) facilitated diffusion. 2- Active transport. a) primary active transport. b) secondary active transport. 3- Osmosis.  Diffusion Random movement of substance either through the membrane directly or in combination with carrier protein down an electrochemical gradient. 1- Simple diffusion. 2- facilitated diffusion. - Simple and facilitated diffusion Do NOT require input of energy = powered by concentration gradient or electrical gradient. - Active transport = uses energy = utilizes ATP.  Simple Diffusion Non-carrier mediated transport down an electrochemical gradient. Diffusion of non-electrolytes (uncharged) from high concentration to low concentration. Diffusion of electrolytes (charged) depend on both chemical, as will as, electrical potential difference.  Rate Of Simple Diffusion Depend On: 1- Amount of substance available. 2- The number of opening in the cell membrane for the substance (pores). 3- Chemical concentration difference. 4- Electrical potential difference. 5- Molecular size of the substance. 6- Lipid solubility. 7- Temperature. Factors Affecting Rate of Diffusion cont… 𝑹𝒂𝒕𝒆 𝒐𝒇 𝒅𝒊𝒇𝒇𝒖𝒔𝒊𝒐𝒏 = 𝑷 𝑿 𝑨 (𝑪𝟏−𝑪𝟐) 1. P = Permeability coefficient. a. Temperature b. Size of molecule c. Solubility in lipids d. Thickness of membrane 2. A = surface area. 3. (C1-C2) = gradient difference: a. Concentration difference b. Electrical difference. c. Pressure difference. Net Flow  Facilitated Diffusion Carrier mediated transport down an electrochemical gradient. e.g. glucose & amino acids.  Features Of Carrier Mediated Transport (Facilitated diffusion) 1- saturation: concentration binding of protein If all protein carriers are occupied, full saturation is achived. i.e. The rate of diffusion reaches a maximum (Vmax) when all the carriers are functioning as rapidly as possible. 2- stereopecificity: The binding site recognize a specific substance D-glucose but not L-glucose. 3- Competition: Chemically similar substances can compete for the same binding site. D- galactose / D-glucose. ---------------------------------------------------------------- {Substance binding site substance protein complex conformational changes release of substance}  Active Transport: Transport (uphill) against electrochemical gradient. Required energy direct. indirect. Required carrier – protein.  1- Primary Active Transport: -Energy is supplied directly from ATP. ATP ADP + P + energy. A. - Sodium-Potassium pump (Na+- K+ pump). - it’s present in all cell membranes. - 3 Na+ in out. - 2 K+ out in. Discovery Na+/K+-ATPase pump was discovered by Jens Christian Skou in 1957. In 1997, he received the Nobel Prize in Chemistry. Characteristic of Na+/K+-ATPase Pump: 1. Carrier protein is formed from α and β subunits. 2. Binding site for Na inside the cell. 3. Binding site for K outside the cell. 4. It has ATPase activity. 5. 3 Na out. 6. 2 K in.  Function: 1. Maintaining Na+ and K+ concentration difference. 2. It’s the basis of nerve signal transmition. 3. Maintaining negative potential inside the cell. 4. Maintains a normal cell volume. B. primary active transport of calcium (Ca ++ ATPase). - sarcoplasmic reticulum (SR). - mitochondria. - in some cell membranes. Function: Maintaining a low Ca²+ concentration inside the cell. C. primary active transport of hydrogen ions H+-K+ ATPase. - stomach. - kidneys. - pump to the lumen. - H+-K+ ATPase inhibitors, are used to treat ulcers (e.g. omeprazole).  2) Secondary Active Transport: Co- transport and counter-transport: - is transport of one or more solutes against an electrochemical gradient, coupled with the transport of another solute down an electrochemical gradient. - ‘’downhill’’ solute is Na+. - Energy is supplied indirectly form primary transport.  Co-transport: - All solutes move in the same direction ‘’ inside cell’’. - e.g.  Na+- glucose Co-transport.  Na+- amino acid Co-transport.  present in the intestinal tract & kidneys. Counter-transport: Na+ is moving to the interior of the cell causing other substance to move out. Ca+ +- Na+ exchange. (present in many cell membranes) Na+- H+ exchange in the kidney. Body Fluids & Electrolytes  objectives At the end of this session, the students should be able to: Identify and describe daily intake and output of water and maintenance of water balance. List and describe of body fluid compartments as intra-cellular fluid (ICF) Extra-cellular fluid (ECF), interstitial fluid, trans-cellular fluid and total body water (TBW). Describe the composition of each fluid compartment, in terms of volume and ions and represent them in graphic forms. Physiology factor influencing body fluid: age, sex, adipose tissue, etc. Pathological factors: Dehydration, fluid infusion.  Human body contain 50-70% water. E.g. – 70 kg man has 42 L of water. – (Kg of water = Liter of water)  FACTORS AFFECTING Infant: 73% Male adult: 60% Female adult: 40-50% Obesity Old age 45%  Body Water Content Infants have low body fat, low bone mass, and are 73% or more water. Total water content declines throughout life. Healthy males are about 60% water; healthy females are around 50% – This difference reflects females’: Higher body fat Smaller amount of skeletal muscle In old age, only about 45% of body weight is water. Daily intake of water Water Intake and Output Regulation of Water Intake Climate Habits Level of physical activity.  Regulation of Water Intake The hypothalamic thirst center is stimulated: – By a decline in plasma volume of 10%–15% – By increases in plasma osmolality of 1–2% In steady state water intake = water loss  Factors that affect the TBW Physiological factors: Age Sex Body fat Climate Physical activity Pathological factors: Vomiting Diarrhea Diseases with excessive loss of water (DM, excessive sweating,…. Blood loss  Fluid Compartments Water occupies two main fluid compartments: –Intracellular fluid (ICF) –Extracellular fluid (ECF) Plasma Interstitial fluid (IF) Fluid Compartments  FLUID COMPARTMENTS EXTRA CELLUAR INTRA CELLULAR FLUID FLUID INTERSTITIAL TRANSCELLULAR PLASMA FLUID FLUID CSF Intra ocular Pleural Peritoneal Synovial Digestive Secretions  Intracellular fluid (ICF) Inside the cell. 2/3 of TBW. High concentration of protein.  Extracellular fluid (ECF) Out side the cell. 1/3 of TBW. 1- Plasma: Fluid circulating in the blood vessels. 1/4 of ECF 2- Interstitial fluid: Fluid bathing the cell. Ultra filtration of plasma. 3/4 of ECF  Plasma and interstitial fluid are almost having the same composition except for high protein concentration in plasma.  Trancecellular fluid compartment: small amount. CSF, GIT fluid, biliary fluid, synovial fluid, intrapelural fluid, intraperitoneal fluid, intrapericardial fluid and intraoccular fluid.  e.g. TBW = 42L. ECF = 14L. ICF = 28L. Plasma = 3.5 L. Interstitial = 10.5 L.  Composition of Body Fluids Water is the universal solvent. Solutes are broadly classified into: – Electrolytes – inorganic salts, all acids and bases, and some proteins – Nonelectrolytes – examples include glucose, lipids, creatinine, and urea – Amount = in moles, osmoles.  concentration 1- Molarity = moles/liter (M/L) 2- Osmolarity = osmoles/liter (osm/L) 3- Osmolality = osmoles/kg (osm/kg)  In biological solutions: Millimoles per liter (mM/L) Milliosmoles per (mOsm/L) 1mM=1/1000 M 1mOsm=1/1000 Osm  Electrolyte Concentration Expressed in milliequivalents per liter (mEq/L), a measure of the number of electrical charges in one liter of solution. mEq/L = (concentration of ion in [mg/L]/the atomic weight of ion)  number of electrical charges on one ion. For single charged ions, 1 mEq = 1 mOsm For bivalent ions, 1 mEq = 1/2 mOsm Constituents of ECF and ICF  Extracellular and Intracellular Fluids Each fluid compartment of the body has a distinctive pattern of electrolytes. Extracellular fluids are similar (except for the high protein content of plasma) – Sodium is the chief cation – Chloride is the major anion  Intracellular fluid has low sodium and chloride – Potassium is the chief cation – Phosphate is the chief anion Each compartment must have almost the same concentration of positive charge (cations) as of negative charge (anion). (Electroneutrality)  Hypokalemia: decrease in K concentration in the ECF. 1-2 mEq/L Hyperkalemia: increase in K 60-100% above normal. Hypernatremia: increase in Na concentration in ECF. Hyponatremia: decrease in Na concentration in the ECF. ‫هللا يوفقن‬ Continuous exchange of Body Fluids  Mechanisms for Movement 3 general mechanisms: 1. simple diffusion (passive) 2. Facilitated transport (passive) 3. Active transport  osmosis Net diffusion of water from a region of high water concentration to region of low water concentration.  Osmotic equilibrium is maintained between intracellular and extracellular fluids: Small changes in concentration of solutes in the extracellular fluid can cause tremendous change in cell volume. Intracellular osmolarity = extracellular osmolarity. ≈ 300 mosm/L Osmosis  Osmosis Shriveled RBCs Normal RBCs Swollen RBCs Hypertonic Solution Isotonic Solution Hypotonic Solution Net movement of Equal movement of water water out of cells into and out of cells Net movement of water into cells  Osmosis If environment is: – Hypertonic: MORE SOLUTES outside cell MORE WATER IN CELL over time, cell loses water – Isotonic: same No change in cell volume – Hypotonic: LESS SOLUTES outside cell LESS WATER IN CELL, more solutes in cell. over time, cell gains water Isotonic solution : - (not swell or shrink ) - 0.9% solution of sodium chloride or 5% glucose. - same in and out.  Hypotonic solution : - (swelling) 0.9% - in is higher than out. Hypertonic solution : - (shrink) 0.9% - out is higher than in Glucose and other solutions administered for nutritive purposes People who can not take adequate amount of food. Slowly. Prepared in isotonic solution. Homeostasis  Homeostasis Homeostasis is the ability to maintain a relatively stable internal environment in an ever-changing outside world The internal environment of the body (ECF)is in a dynamic state of equilibrium All different body systems operate in harmony to provide homeostasis  Homeostatic Control Mechanisms The variable produces a change in the body The three interdependent components of control mechanisms are: – Receptor – monitors the environments and responds to changes (stimuli) – Control center – determines the set point at which the variable is maintained – Effector – provides the means to respond to the stimulus  Regulation of body functions 1. Nervous system - sensory input. - central nervous system. - motor out put. 2. Hormonal system of regulation. - Endocrine gland. Pancreas, thyroid e.g. : insulin control glucose level. Homeostatic Control Mechanisms 3 Input: Control center 4 Output: Information Information sent sent along along efferent afferent pathway to pathway to Receptor (sensor) Effector 2 Change detected by receptor 5 Response of effector feeds back to influence 1 Stimulus: magnitude of Produces stimulus and change returns in variable variable to homeostasis Variable (in homeostasis) Feedback  Homeostatic Imbalance Disturbance of homeostasis or the body’s normal equilibrium.  Homeostasis & Controls Successful compensation – Homeostasis reestablished Failure to compensate – Pathophysiology Illness Death  Lecture 4 Changes in The Body Fluid Compartments (ECF & ICF) and Edema Fluid Compartments Constituents of ECF and ICF  Osmosis Shriveled RBCs Normal RBCs Swollen RBCs Hypertonic Solution Isotonic Solution Hypotonic Solution Net movement of Equal movement of water water out of cells into and out of cells Net movement of water into cells Volumes And Osmolarities of ECF and ICF In Abnormal States. Some factors can cause the change: - dehydration - intravenous infusion (IV) - abnormal sweating. - etc..  Changes in volume : 1. Volume contraction. 2. Volume expansion.  Changes in volume Volume contraction Volume expansion removing Adding 1- isotonic solution. 1- isotonic solution. 2- hypertonic solution. 2- hypertonic solution. 3- hypotonic solution. 3- hypotonic solution. 1- Loss of iso-osmotic fluid e.g. Diarrhea  Volume contraction: 1. Diarrhea. - osmolarity of fluid lost ≈ osmolarity of ECF (loss of isosmotic fluid). - volume in ECF. - arterial pressure. 2. Loss of hypotonic solution e.g. Water deprivation Hyperosmotoc dehydration 2. Water deprivation : - Osmolarity and volume will change. - Osmolarity in both ECF and ICF. - Volume in both ECF and ICF. 3- Loss of hypertonic sol. e.g. Adrenal insufficiency Osmolarity Hypo-osmotic dehydration 3. Loss of hypertonic solution e.g. Adrenal insufficiency: i.e. Aldosterone deficiency. - Na+ in the ECF. - osmolarity in both. - in ECF volume. - in ICF volume. Volume Expansion 1. Adding of isotonic NaCl.  Volume Expansion 1. Infusion of isotonic NaCl. - in ECF volume. - No change in osmolarity. - Isomotic expansion. 2- High NaCl intake 2. High NaCl intake. - eating salt. - osmolarity in both. - volume of ICF. - volume of ECF. - hyperosmotic volume expansion. 3- Adding hypotonic solution e.g. Syndrome of inappropriate antidiurtic hormone (SIADH) volume osmolarity  Edema Edema: is excessive fluid in the tissues Intracellular Extracellular Edema occurs mainly in the ECF compartment  Extracellular Edema common clinical cause is excessive capillary fluid filtration. Heart failure. capillary pressure filtration. edema Intracellular Edema: inflammation of tissues. membrane permeability. Na inside cells. water edema ‫هللا يوفقن‬