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Transport across cell membrane

Transport across the cell membrane is necessary to maintain cellular function. There are three main types of transport: passive transport which includes diffusion, facilitated diffusion, and osmosis and does not require energy; active transport which uses energy and transports molecules against their concentration gradient, including primary active transport using ATP and secondary active transport utilizing ion gradients; and vesicular transport which transports larger molecules through vesicles via endocytosis, exocytosis, and transcytosis. Specialized proteins are involved in each of these transport mechanisms to regulate the passage of substances into and out of cells.

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Transport across the cell membrane Dr AnuPriya J 9/28/2018 msrmc 1
• Transport of substances across the cell membrane is necessary to maintain the normal functioning of the cells in our body. 9/28/2018 msrmc 2 Introduction
Transport across the cell membrane  Lipid soluble substances, water & urea can easily pass through the lipid bilayer of the cell membrane The lipid bilayer of the cell membrane is impermeable to lipid insoluble substances such as ions & charged or polar molecules like glucose These substances pass through specialized protein channels, carrier proteins & active pump mechanisms • Large macromolecules are transported through vesicles. 9/28/2018 msrmc 3
Types • Passive transport – Diffusion – simple, facilitated – Osmosis • Active transport – Primary – Secondary • Vesicular transport – Endocytosis – Exocytosis – Transcytosis 9/28/2018 msrmc 4
NO ENERGY NEEDED: Diffusion Osmosis Facilitated Diffusion ENERGY NEEDED: Active Transport ANALOGY: 9/28/2018 msrmc 5
NO ENERGY NEEDED: Diffusion Osmosis Facilitated Diffusion ENERGY NEEDED: Active Transport ANALOGY: 9/28/2018 msrmc 6
PASSIVE TRANSPORT Diffusion- Simple Facilitated Osmosis 9/28/2018 msrmc 7
Diffusion-simple • It is the movement of ions or molecules from a region of their high concentration to a region of their low concentration, without the expenditure of energy • Movement is towards the concentration gradient until an equilibrium is achieved. 9/28/2018 msrmc 8
9/28/2018 msrmc 9
Distilled water Potassium manganate (vii) crystals a) The crystals starts to dissolve, forming a region of high concentration of solute molecules. b) The molecules diffuse out along the concentration gradient in all direction. c) Eventually the molecules spread throughout the water uniformly. Purple solution A sample experiment to illustrate the physical process of diffusion 9/28/2018 msrmc 10
Factors affecting the rate of diffusion 9/28/2018 msrmc 11 Factor Effect on the rate of simple diffusion Diffusion gradient/ concentration difference The steeper, the higher the rate Size of molecules or ions/ Molecular weight The smaller the size, the higher the rate Indirectly proportional Temperature The higher the temperature, the higher the rate Diffusion medium Rate in gas > rate in liquid > rate in solid Surface area The larger the surface area, the higher the rate
Factors affecting the rate of diffusion 9/28/2018 msrmc 12 Factor Effect on the rate of simple diffusion Solubility Directly proportional Thickness of membrane Indirectly proportional FICK’S LAW OF DIFFUSION
Simple diffusion Diffusion through lipid matrix • Lipophilic/hydrophobic/nonpolar/uncharged substances such as O2,CO2,N2,fatty acids, alcohol, steroid hormones, etc., • Water as it is a small molecule with high kinetic energy • Urea 9/28/2018 msrmc 13
Simple diffusion Ionic diffusion – through channel proteins • Ions diffuse through the ion channels. • They are either open or gated. • Open/leak channels – ex: K+ channels • Gated channels open when stimulus is given – Voltage gated – Ligand gated – Mechano sensitive gated 9/28/2018 msrmc 14
Inhaled and exhaled air O2 CO2 Oxygenated bloodDeoxygenated blood Red blood cell Capillary wall Alveolus wall Air sac GASEOUS EXHANGE BY SIMPLE DIFFUSION IN THE ALVEOLUS 9/28/2018 msrmc 15
Facilitated diffusion • Facilitated diffusion is the movement of specific molecules (or ions) across the plasma membrane, assisted by a carrier protein. • The direction of movement is down the concentration gradient of the molecules concerned. • No energy required. 9/28/2018 msrmc 16
Facilitated diffusion 9/28/2018 msrmc 17
Difference between carrier proteins & channel proteins • Carrier proteins bind to larger molecules, and change their shape so molecules can diffuse through. • Channel proteins provide water filled pores for charged ions to pass through 9/28/2018 msrmc 18
Difference between simple and passive diffusion Simple diffusion Facililated diffusion Mechanism Concentration gradient Concentration gradient Through carrier molecule Rate of diffusion Increase with increase in concentration gradient Reaches plateau (saturation of carrier protein) Example Ions through ion channels GLUT for glucose 9/28/2018 msrmc 19
0smosis • Osmosis is the movement of water molecules (solvent) through a selectively permeable membrane/ semipermeable membrane like the cell membrane. • Water diffuses across a membrane from an area of high concentration to an area of low concentration. 9/28/2018 msrmc 20
Osmosis • Semi-permeable membrane is permeable to water, but not to the solute i.e.,sugar 9/28/2018 msrmc 21
9/28/2018 msrmc 22
Tonicity • Osmolality of a solution relative to plasma • Sodium ion is the major contributor to tonicity of ECF 9/28/2018 msrmc 23
Hypertonic Solutions •Contain a high concentration of solute relative to another solution (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 shrivel. 9/28/2018 msrmc 24
Hypotonic Solutions • Contain a low concentration of solute relative to another solution (e.g. the cell's cytoplasm). • When a cell is placed in a hypotonic solution, the water diffuses into the cell, causing the cell to swell and possibly explode. 9/28/2018 msrmc 25
Isotonic Solutions • Contain the same concentration of solute as another solution (e.g. the cell's cytoplasm). • 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. 9/28/2018 msrmc 26
Click9/28/2018 msrmc 27
Hypertonic solution Isotonic solution Hypotonic solution Remains of cell surface membrane Crenation: Red blood cell shrinks and turns ’spiky’ Red blood cell Swells up Haemolysis: Red blood cell finally burst CRENATION AND HAEMOLYSIS OF RED BLOOD CELL 9/28/2018 msrmc 28
• Isotonic solution – 0.9% NaCl, 5% dextrose in water • Hypotonic solution – treat dehydration • Hypertonic solution – mannitol – treat cerebral edema 9/28/2018 msrmc 29
9/28/2018 msrmc 33
ACTIVE TRANSPORT Primary secondary 9/28/2018 msrmc 34
Active Transport • Molecules move against the concentration gradient (low to high) • Energy must be provided • Exhibit saturation kinetics 9/28/2018 35Dr.Anu Priya J
9/28/2018 36Dr.Anu Priya J
• Active transport is divided into two types according to the source of the energy used to cause the transport: • 1. Primary active transport • 2. Secondary active transport. Active Transport 9/28/2018 37Dr.Anu Priya J
Primary active transport • They use the energy directly from the hydrolysis of ATP. Sodium potassium Pump Calcium pump Hydrogen Potassium pump 9/28/2018 38Dr.Anu Priya J
Sodium potassium pump 9/28/2018 39Dr.Anu Priya J
9/28/2018 40Dr.Anu Priya J
Sodium potassium pump - present in all eukaryotic cells Functions: 1. Maintains sodium potassium concentration difference across the cell membrane. 2. Maintains volume of the cell. 3. Causes negative electrical charge inside the cell – electrogenic pump 4. Essential for oxygen utilization by the kidneys 9/28/2018 Dr.Anu Priya J 41
Calcium pump 9/28/2018 42Dr.Anu Priya J
Secondary active transport • Energy utilised in the transport of one substance helps in the movement of the other substance. • Energy is derived secondarily, from energy that has been stored in the form of ionic concentration differences of secondary molecular or ionic substances between the two sides of a cell membrane, created originally by primary active transport. 9/28/2018 43Dr.Anu Priya J
Co-transport-symport • The transport of Na+ via its concentration gradient is coupled to the transport of other substances in the same direction • Carrier protein • E.g SGLT • Sodium glucose Co-transport 9/28/2018 44Dr.Anu Priya J
9/28/2018 45Dr.Anu Priya J
9/28/2018 46Dr.Anu Priya J
Counter transport • The transport of Na+ via its concentration gradient is coupled to the transport of other substance in the opposite direction Sodium-Hydrogen counter transport in the proximal tubule of the kidneys Sodium-Calcium exchanger in the cardiac cells 9/28/2018 47Dr.Anu Priya J
Counter transport 9/28/2018 48Dr.Anu Priya J
• Cardiac glycosides -Digitalis & Ouabain – management of heart failure • Inhibits Na+-K+ pump • Accumulation of Na+ inside the cell & prevention of K+ influx • Intracellular accumulation of Na+ , decreases Na+ gradient from outside to inside. Applied aspects 9/28/2018 49Dr.Anu Priya J
• Calcium efflux through sodium-calcium exchanger in the membrane utilizes sodium gradient. • Decreased sodium gradient decreases calcium efflux causing increase in cytosolic calcium concentration, that promotes myocardial contractility. Applied aspects 9/28/2018 50Dr.Anu Priya J
9/28/2018 Dr.Anu Priya J 51
Applied aspects • Activation of Na+-K+ pump: Thyroxine, Insulin, Aldosterone • Inhibition of Na+-K+ pump: Dopamine, Digitalis, Hypoxia, Hypothermia 9/28/2018 52Dr.Anu Priya J
Difference between Facilitated diffusion and Active transport • In both instances, transport depends on carrier proteins that penetrate through the cell membrane, as is true for facilitated diffusion. However, in active transport, the carrier protein functions differently from the carrier in facilitated diffusion because it is capable of imparting energy to the transported substance to move it against the electrochemical gradient. 9/28/2018 53Dr.Anu Priya J
VESICULAR TRANSPORT 9/28/2018 msrmc 54
9/28/2018 msrmc 55
Vesicular transport • Endocytosis • Exocytosis • Transcytosis 9/28/2018 msrmc 56
Endocytosis/Exocytosis • For substances the cell needs to take in (endo = in) or expel (exo = out), that are too large for passive or active transport 9/28/2018 msrmc 57
9/28/2018 msrmc 58
Endocytosis • The material makes contact with the cell membrane • Cell membrane then invaginates • Invagination is then pinched off leaving the cell membrane intact 9/28/2018 msrmc 59
Types of Endocytosis 1. receptor mediated endocytosis 2. phagocytosis (solids) 3. pinocytosis (liquids) 9/28/2018 msrmc 60
9/28/2018 msrmc 61 Types of Endocytosis
Ex: • White Blood Cells surround and engulf bacteria by Phagocytosis. • Pinocytosis – amino acids, fatty acids • Receptor mediated endocytosis – LDL, Nerve growth factor, vitamins, hormones, HIV virus entering the T cell etc., 9/28/2018 msrmc 62
Exocytosis • The process of release of macromolecules from the cells to the exterior. • Vesicles containing material to be exposed, bind to the cell membrane • Area of fusion breaks down leaving the contents of the vesicle outside & the cell membrane intact • Reverse pinocytosis or emeiocytosis • Requires calcium & energy • Secretory granules, hormones 9/28/2018 msrmc 63
9/28/2018 msrmc 64 Exocytosis
9/28/2018 msrmc 65 Exocytosis
• Vesicles endocytosed on one side of the cell; exocytosed on the opposite side. • Caveolin mediated (Rafts & Caveolae) • Also known as cytopempsis • Transport of substances across the endothelial cells of blood vessels to interstitial fluid 9/28/2018 msrmc 66 Transcytosis
Transcytosis 9/28/2018 msrmc 67
Thank you 9/28/2018 msrmc 68
9/28/2018 69Dr.Anu Priya J
9/28/2018 Dr.Anu Priya J 70 Hydrogen Potassium pump H+-K+ ATPase
Hydrogen Potassium pump H+-K+ ATPase • Gastric glands - parietal cells - hydrochloric acid secretion • Renal tubules - intercalated cells in the late distal tubules and cortical collecting ducts. 9/28/2018 71Dr.Anu Priya J
• Present in lysosome and endoplasmic reticulum • Pumps proton from cytosol into these organelles. Proton pump H+ ATPase 9/28/2018 72Dr.Anu Priya J
9/28/2018 msrmc 74
• In counter-transport, sodium ions again attempt to diffuse to the interior of the cell because of their • large concentration gradient. However, this time, the substance to be transported is on the inside of the • cell and must be transported to the outside. Therefore, the sodium ion binds to the carrier protein • where it projects to the exterior surface of the membrane, while the substance to be countertransported • binds to the interior projection of the carrier protein. Once both have bound, a • conformational change occurs, and energy released by the sodium ion moving to the interior causes • the other substance to move to the exterior. 9/28/2018 75Dr.Anu Priya J
• Different substances that are actively transported through at least some cell membranes include sodium ions, potassium ions, calcium ions, iron ions, hydrogen ions, chloride ions, iodide ions, urate ions, several different sugars, and most of the amino acids. 9/28/2018 76Dr.Anu Priya J
• At times, a large concentration of a substance is required in the intracellular fluid even though the • extracellular fluid contains only a small concentration. This is true, for instance, for potassium ions. • Conversely, it is important to keep the concentrations of other ions very low inside the cell even though • their concentrations in the extracellular fluid are great. This is especially true for sodium ions. Neither • of these two effects could occur by simple diffusion because simple diffusion eventually equilibrates • concentrations on the two sides of the membrane. Instead, some energy source must cause excess • movement of potassium ions to the inside of cells and excess movement of sodium ions to the outside • of cells. When a cell membrane moves molecules or ions "uphill" against a concentration gradient (or • "uphill" against an electrical or pressure gradient), the process is called active transport. 9/28/2018 77Dr.Anu Priya J
ACTIVE TRANSPORT • A process in which molecules move against the concentration gradient across the cell membrane with expenditure of energy. • This energy is provided by ATP. 9/28/2018 78Dr.Anu Priya J
Sodium potassium pump 9/28/2018 79Dr.Anu Priya J
Sodium potassium pump 9/28/2018 80Dr.Anu Priya J
9/28/2018 81Dr.Anu Priya J
• As with other enzymes, the Na+-K+ ATPase pump can run in reverse. If the electrochemical gradients • for Na+ and K+ are experimentally increased enough so that the energy stored in their gradients is • greater than the chemical energy of ATP hydrolysis, these ions will move down their concentration • gradients and the Na+-K+ pump will synthesize ATP from ADP and phosphate. The phosphorylated • form of the Na+-K+ pump, therefore, can either donate its phosphate to ADP to produce ATP or use the • energy to change its conformation and pump Na+ out of the cell and K+ into the cell. The relative • concentrations of ATP, ADP, and phosphate, as well as the electrochemical gradients for Na+ and K+, • determine the direction of the enzyme reaction. For some cells, such as electrically active nerve cells, • 60 to 70 percent of the cells' energy requirement may be devoted to pumping Na+ out of the cell and • K+ into the cell. 9/28/2018 82Dr.Anu Priya J
• The Na+-K+ Pump Is Important For Controlling Cell Volume • One of the most important functions of the Na+-K+ pump is to control the volume of each cell. Without • function of this pump, most cells of the body would swell until they burst. The mechanism for controlling • the volume is as follows: Inside the cell are large numbers of proteins and other organic molecules that • cannot escape from the cell. Most of these are negatively charged and therefore attract large numbers • of potassium, sodium, and other positive ions as well. All these molecules and ions then cause osmosis • of water to the interior of the cell. Unless this is checked, the cell will swell indefinitely until it bursts. • The normal mechanism for preventing this is the Na+-K+ pump. Note again that this device pumps • three Na+ ions to the outside of the cell for every two K+ ions pumped to the interior. Also, the • Guyton & Hall: Textbook of Medical Physiology, 12e [Vish'aAlc] tive Transport' of Substances Through Membranes • 93 / 1921 • membrane is far less permeable to sodium ions than to potassium ions, so once the sodium ions are on • the outside, they have a strong tendency to stay there. Thus, this represents a net loss of ions out of • the cell, which initiates osmosis of water out of the cell as well. • If a cell begins to swell for any reason, this automatically activates the Na+-K+ pump, moving still more • ions to the exterior and carrying water with them. Therefore, the Na+-K+ pump performs a continual • surveillance role in maintaining normal cell volume. 9/28/2018 83Dr.Anu Priya J
• Electrogenic Nature of the Na+-K+ Pump • page 53 • page 54 • The fact that the Na+-K+ pump moves three Na+ ions to the exterior for every two K+ ions to the • interior means that a net of one positive charge is moved from the interior of the cell to the exterior for • each cycle of the pump. This creates positivity outside the cell but leaves a deficit of positive ions • inside the cell; that is, it causes negativity on the inside. Therefore, the Na+-K+ pump is said to be • electrogenic because it creates an electrical potential across the cell membrane. As discussed in • Chapter 5, this electrical potential is a basic requirement in nerve and muscle fibers for transmitting • nerve and muscle signals. 9/28/2018 84Dr.Anu Priya J
Primary Active Transport of Hydrogen Ions • At two places in the body, primary active transport of hydrogen ions is important: (1) in the gastric glands of the stomach and (2) in the late distal tubules and cortical collecting ducts of the kidneys. • In the gastric glands, the deep-lying parietal cells have the most potent primary active mechanism for transporting hydrogen ions of any part of the body. This is the basis for secreting hydrochloric acid in the stomach digestive secretions. At the secretory ends of the gastric gland parietal cells, the hydrogen ion concentration is increased as much as a millionfold and then released into the stomach along with chloride ions to form hydrochloric acid. • In the renal tubules are special intercalated cells in the late distal tubules and cortical collecting ducts that also transport hydrogen ions by primary active transport. In this case, large amounts of hydrogen ions are secreted from the blood into the urine for the purpose of eliminating excess hydrogen ions from the body fluids. The hydrogen ions can be secreted into the urine against a concentration gradient of about 900-fold. 9/28/2018 85Dr.Anu Priya J
Secondary active transport • Energy utilised in the transport of one substance helps in the movement of the other substance. 9/28/2018 86Dr.Anu Priya J
• Secondary Active Transport-Co-Transport • When sodium ions are transported out of cells by primary active transport, a large concentration gradient of sodium ions across the cell membrane usually develops-high concentration outside the cell and low concentration inside. • This gradient represents a storehouse of energy because the excess sodium outside the cell membrane is always attempting to diffuse to the interior. • Under appropriate conditions, this diffusion energy of sodium can pull other substances along with the sodium through the cell membrane. This phenomenon is called co-transport; it is one form of secondary active transport. • For sodium to pull another substance along with it, a coupling mechanism is required. This is achieved by means of still another carrier protein in the cell membrane. The carrier in this instance serves as an attachment point for both the sodium ion and the substance to be co-transported. • Once they both are attached, the energy gradient of the sodium ion causes both the sodium ion and the other substance to be transported together to the interior of the cell. 9/28/2018 87Dr.Anu Priya J
Proton pump H+ ATPase 9/28/2018 88Dr.Anu Priya J

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In this document
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Introduction to transport across the cell membrane, highlighting its necessity for cell function.

Different types of transport across cell membranes: passive (diffusion, osmosis) and active transport.

Overview of passive transport methods including diffusion, osmosis, and facilitated diffusion.

Simple diffusion described: movement from high to low concentration explained with an experiment.

Factors affecting diffusion rates including concentration gradient, molecule size, and temperature.

Detailed mechanisms of simple and ionic diffusion through membrane channels and carriers.

Explanation of gaseous exchange process by simple diffusion in alveoli.

Description of facilitated diffusion, the role of carrier proteins, and its differing mechanics.

Differences between simple diffusion and facilitated diffusion, with specific examples provided.Definition of osmosis and its implications for water movement across selectively permeable membranes.

Explanation of hypertonic, hypotonic, and isotonic solutions with effects on cell volume.

Effects of different tonic solutions on red blood cells: crenation and hemolysis are illustrated.

Introduction to active transport, its subtypes, and the concept of energy utilization in transport.

Details on primary active transport mechanisms with specific examples including sodium-potassium pump.

Explanation of secondary active transport, describing co-transport and counter transport mechanisms.

Practical applications of concepts related to active transport relevant to medical conditions.

Comparison between facilitated diffusion and active transport to clarify their distinctions. Explanation of vesicular transport methods: endocytosis, exocytosis, and transcytosis as transport modes.

Detailed processes of endocytosis including receptor-mediated, phagocytosis, and pinocytosis.

Description of exocytosis and its importance in the release of cellular materials.

Description of transcytosis and its role in endothelial cells for substance transport.

Overview of the hydrogen-potassium pump, emphasizing its functions among gastric and renal cells.

Explanation of counter transport, sodium movement, and its role in active transport processes.

Summary of active transport functions, highlighting sodium-potassium pump's role in cell volume maintenance.

Transport across cell membrane

  • 1.
    Transport across the cellmembrane Dr AnuPriya J 9/28/2018 msrmc 1
  • 2.
    • Transport ofsubstances across the cell membrane is necessary to maintain the normal functioning of the cells in our body. 9/28/2018 msrmc 2 Introduction
  • 3.
    Transport across the cellmembrane  Lipid soluble substances, water & urea can easily pass through the lipid bilayer of the cell membrane The lipid bilayer of the cell membrane is impermeable to lipid insoluble substances such as ions & charged or polar molecules like glucose These substances pass through specialized protein channels, carrier proteins & active pump mechanisms • Large macromolecules are transported through vesicles. 9/28/2018 msrmc 3
  • 4.
    Types • Passive transport –Diffusion – simple, facilitated – Osmosis • Active transport – Primary – Secondary • Vesicular transport – Endocytosis – Exocytosis – Transcytosis 9/28/2018 msrmc 4
  • 5.
    NO ENERGY NEEDED: Diffusion Osmosis FacilitatedDiffusion ENERGY NEEDED: Active Transport ANALOGY: 9/28/2018 msrmc 5
  • 6.
    NO ENERGY NEEDED: Diffusion Osmosis FacilitatedDiffusion ENERGY NEEDED: Active Transport ANALOGY: 9/28/2018 msrmc 6
  • 7.
  • 8.
    Diffusion-simple • It isthe movement of ions or molecules from a region of their high concentration to a region of their low concentration, without the expenditure of energy • Movement is towards the concentration gradient until an equilibrium is achieved. 9/28/2018 msrmc 8
  • 9.
  • 10.
    Distilled water Potassium manganate (vii) crystals a)The crystals starts to dissolve, forming a region of high concentration of solute molecules. b) The molecules diffuse out along the concentration gradient in all direction. c) Eventually the molecules spread throughout the water uniformly. Purple solution A sample experiment to illustrate the physical process of diffusion 9/28/2018 msrmc 10
  • 11.
    Factors affecting therate of diffusion 9/28/2018 msrmc 11 Factor Effect on the rate of simple diffusion Diffusion gradient/ concentration difference The steeper, the higher the rate Size of molecules or ions/ Molecular weight The smaller the size, the higher the rate Indirectly proportional Temperature The higher the temperature, the higher the rate Diffusion medium Rate in gas > rate in liquid > rate in solid Surface area The larger the surface area, the higher the rate
  • 12.
    Factors affecting therate of diffusion 9/28/2018 msrmc 12 Factor Effect on the rate of simple diffusion Solubility Directly proportional Thickness of membrane Indirectly proportional FICK’S LAW OF DIFFUSION
  • 13.
    Simple diffusion Diffusion throughlipid matrix • Lipophilic/hydrophobic/nonpolar/uncharged substances such as O2,CO2,N2,fatty acids, alcohol, steroid hormones, etc., • Water as it is a small molecule with high kinetic energy • Urea 9/28/2018 msrmc 13
  • 14.
    Simple diffusion Ionic diffusion– through channel proteins • Ions diffuse through the ion channels. • They are either open or gated. • Open/leak channels – ex: K+ channels • Gated channels open when stimulus is given – Voltage gated – Ligand gated – Mechano sensitive gated 9/28/2018 msrmc 14
  • 15.
    Inhaled and exhaledair O2 CO2 Oxygenated bloodDeoxygenated blood Red blood cell Capillary wall Alveolus wall Air sac GASEOUS EXHANGE BY SIMPLE DIFFUSION IN THE ALVEOLUS 9/28/2018 msrmc 15
  • 16.
    Facilitated diffusion • Facilitateddiffusion is the movement of specific molecules (or ions) across the plasma membrane, assisted by a carrier protein. • The direction of movement is down the concentration gradient of the molecules concerned. • No energy required. 9/28/2018 msrmc 16
  • 17.
  • 18.
    Difference between carrier proteins& channel proteins • Carrier proteins bind to larger molecules, and change their shape so molecules can diffuse through. • Channel proteins provide water filled pores for charged ions to pass through 9/28/2018 msrmc 18
  • 19.
    Difference between simple andpassive diffusion Simple diffusion Facililated diffusion Mechanism Concentration gradient Concentration gradient Through carrier molecule Rate of diffusion Increase with increase in concentration gradient Reaches plateau (saturation of carrier protein) Example Ions through ion channels GLUT for glucose 9/28/2018 msrmc 19
  • 20.
    0smosis • Osmosis isthe movement of water molecules (solvent) through a selectively permeable membrane/ semipermeable membrane like the cell membrane. • Water diffuses across a membrane from an area of high concentration to an area of low concentration. 9/28/2018 msrmc 20
  • 21.
    Osmosis • Semi-permeable membraneis permeable to water, but not to the solute i.e.,sugar 9/28/2018 msrmc 21
  • 22.
  • 23.
    Tonicity • Osmolality ofa solution relative to plasma • Sodium ion is the major contributor to tonicity of ECF 9/28/2018 msrmc 23
  • 24.
    Hypertonic Solutions •Contain ahigh concentration of solute relative to another solution (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 shrivel. 9/28/2018 msrmc 24
  • 25.
    Hypotonic Solutions • Containa low concentration of solute relative to another solution (e.g. the cell's cytoplasm). • When a cell is placed in a hypotonic solution, the water diffuses into the cell, causing the cell to swell and possibly explode. 9/28/2018 msrmc 25
  • 26.
    Isotonic Solutions • Containthe same concentration of solute as another solution (e.g. the cell's cytoplasm). • 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. 9/28/2018 msrmc 26
  • 27.
  • 28.
    Hypertonic solution Isotonicsolution Hypotonic solution Remains of cell surface membrane Crenation: Red blood cell shrinks and turns ’spiky’ Red blood cell Swells up Haemolysis: Red blood cell finally burst CRENATION AND HAEMOLYSIS OF RED BLOOD CELL 9/28/2018 msrmc 28
  • 29.
    • Isotonic solution– 0.9% NaCl, 5% dextrose in water • Hypotonic solution – treat dehydration • Hypertonic solution – mannitol – treat cerebral edema 9/28/2018 msrmc 29
  • 30.
  • 31.
  • 32.
    Active Transport • Moleculesmove against the concentration gradient (low to high) • Energy must be provided • Exhibit saturation kinetics 9/28/2018 35Dr.Anu Priya J
  • 33.
  • 34.
    • Active transportis divided into two types according to the source of the energy used to cause the transport: • 1. Primary active transport • 2. Secondary active transport. Active Transport 9/28/2018 37Dr.Anu Priya J
  • 35.
    Primary active transport •They use the energy directly from the hydrolysis of ATP. Sodium potassium Pump Calcium pump Hydrogen Potassium pump 9/28/2018 38Dr.Anu Priya J
  • 36.
  • 37.
  • 38.
    Sodium potassium pump -present in all eukaryotic cells Functions: 1. Maintains sodium potassium concentration difference across the cell membrane. 2. Maintains volume of the cell. 3. Causes negative electrical charge inside the cell – electrogenic pump 4. Essential for oxygen utilization by the kidneys 9/28/2018 Dr.Anu Priya J 41
  • 39.
  • 40.
    Secondary active transport •Energy utilised in the transport of one substance helps in the movement of the other substance. • Energy is derived secondarily, from energy that has been stored in the form of ionic concentration differences of secondary molecular or ionic substances between the two sides of a cell membrane, created originally by primary active transport. 9/28/2018 43Dr.Anu Priya J
  • 41.
    Co-transport-symport • The transportof Na+ via its concentration gradient is coupled to the transport of other substances in the same direction • Carrier protein • E.g SGLT • Sodium glucose Co-transport 9/28/2018 44Dr.Anu Priya J
  • 42.
  • 43.
  • 44.
    Counter transport • Thetransport of Na+ via its concentration gradient is coupled to the transport of other substance in the opposite direction Sodium-Hydrogen counter transport in the proximal tubule of the kidneys Sodium-Calcium exchanger in the cardiac cells 9/28/2018 47Dr.Anu Priya J
  • 45.
  • 46.
    • Cardiac glycosides-Digitalis & Ouabain – management of heart failure • Inhibits Na+-K+ pump • Accumulation of Na+ inside the cell & prevention of K+ influx • Intracellular accumulation of Na+ , decreases Na+ gradient from outside to inside. Applied aspects 9/28/2018 49Dr.Anu Priya J
  • 47.
    • Calcium effluxthrough sodium-calcium exchanger in the membrane utilizes sodium gradient. • Decreased sodium gradient decreases calcium efflux causing increase in cytosolic calcium concentration, that promotes myocardial contractility. Applied aspects 9/28/2018 50Dr.Anu Priya J
  • 48.
  • 49.
    Applied aspects • Activationof Na+-K+ pump: Thyroxine, Insulin, Aldosterone • Inhibition of Na+-K+ pump: Dopamine, Digitalis, Hypoxia, Hypothermia 9/28/2018 52Dr.Anu Priya J
  • 50.
    Difference between Facilitateddiffusion and Active transport • In both instances, transport depends on carrier proteins that penetrate through the cell membrane, as is true for facilitated diffusion. However, in active transport, the carrier protein functions differently from the carrier in facilitated diffusion because it is capable of imparting energy to the transported substance to move it against the electrochemical gradient. 9/28/2018 53Dr.Anu Priya J
  • 51.
  • 52.
  • 53.
    Vesicular transport • Endocytosis •Exocytosis • Transcytosis 9/28/2018 msrmc 56
  • 54.
    Endocytosis/Exocytosis • For substancesthe cell needs to take in (endo = in) or expel (exo = out), that are too large for passive or active transport 9/28/2018 msrmc 57
  • 55.
  • 56.
    Endocytosis • The materialmakes contact with the cell membrane • Cell membrane then invaginates • Invagination is then pinched off leaving the cell membrane intact 9/28/2018 msrmc 59
  • 57.
    Types of Endocytosis 1.receptor mediated endocytosis 2. phagocytosis (solids) 3. pinocytosis (liquids) 9/28/2018 msrmc 60
  • 58.
  • 59.
    Ex: • White BloodCells surround and engulf bacteria by Phagocytosis. • Pinocytosis – amino acids, fatty acids • Receptor mediated endocytosis – LDL, Nerve growth factor, vitamins, hormones, HIV virus entering the T cell etc., 9/28/2018 msrmc 62
  • 60.
    Exocytosis • The processof release of macromolecules from the cells to the exterior. • Vesicles containing material to be exposed, bind to the cell membrane • Area of fusion breaks down leaving the contents of the vesicle outside & the cell membrane intact • Reverse pinocytosis or emeiocytosis • Requires calcium & energy • Secretory granules, hormones 9/28/2018 msrmc 63
  • 61.
  • 62.
  • 63.
    • Vesicles endocytosedon one side of the cell; exocytosed on the opposite side. • Caveolin mediated (Rafts & Caveolae) • Also known as cytopempsis • Transport of substances across the endothelial cells of blood vessels to interstitial fluid 9/28/2018 msrmc 66 Transcytosis
  • 64.
  • 65.
  • 66.
  • 67.
    9/28/2018 Dr.Anu PriyaJ 70 Hydrogen Potassium pump H+-K+ ATPase
  • 68.
    Hydrogen Potassium pump H+-K+ATPase • Gastric glands - parietal cells - hydrochloric acid secretion • Renal tubules - intercalated cells in the late distal tubules and cortical collecting ducts. 9/28/2018 71Dr.Anu Priya J
  • 69.
    • Present inlysosome and endoplasmic reticulum • Pumps proton from cytosol into these organelles. Proton pump H+ ATPase 9/28/2018 72Dr.Anu Priya J
  • 70.
  • 71.
    • In counter-transport,sodium ions again attempt to diffuse to the interior of the cell because of their • large concentration gradient. However, this time, the substance to be transported is on the inside of the • cell and must be transported to the outside. Therefore, the sodium ion binds to the carrier protein • where it projects to the exterior surface of the membrane, while the substance to be countertransported • binds to the interior projection of the carrier protein. Once both have bound, a • conformational change occurs, and energy released by the sodium ion moving to the interior causes • the other substance to move to the exterior. 9/28/2018 75Dr.Anu Priya J
  • 72.
    • Different substancesthat are actively transported through at least some cell membranes include sodium ions, potassium ions, calcium ions, iron ions, hydrogen ions, chloride ions, iodide ions, urate ions, several different sugars, and most of the amino acids. 9/28/2018 76Dr.Anu Priya J
  • 73.
    • At times,a large concentration of a substance is required in the intracellular fluid even though the • extracellular fluid contains only a small concentration. This is true, for instance, for potassium ions. • Conversely, it is important to keep the concentrations of other ions very low inside the cell even though • their concentrations in the extracellular fluid are great. This is especially true for sodium ions. Neither • of these two effects could occur by simple diffusion because simple diffusion eventually equilibrates • concentrations on the two sides of the membrane. Instead, some energy source must cause excess • movement of potassium ions to the inside of cells and excess movement of sodium ions to the outside • of cells. When a cell membrane moves molecules or ions "uphill" against a concentration gradient (or • "uphill" against an electrical or pressure gradient), the process is called active transport. 9/28/2018 77Dr.Anu Priya J
  • 74.
    ACTIVE TRANSPORT • Aprocess in which molecules move against the concentration gradient across the cell membrane with expenditure of energy. • This energy is provided by ATP. 9/28/2018 78Dr.Anu Priya J
  • 75.
  • 76.
  • 77.
  • 78.
    • As withother enzymes, the Na+-K+ ATPase pump can run in reverse. If the electrochemical gradients • for Na+ and K+ are experimentally increased enough so that the energy stored in their gradients is • greater than the chemical energy of ATP hydrolysis, these ions will move down their concentration • gradients and the Na+-K+ pump will synthesize ATP from ADP and phosphate. The phosphorylated • form of the Na+-K+ pump, therefore, can either donate its phosphate to ADP to produce ATP or use the • energy to change its conformation and pump Na+ out of the cell and K+ into the cell. The relative • concentrations of ATP, ADP, and phosphate, as well as the electrochemical gradients for Na+ and K+, • determine the direction of the enzyme reaction. For some cells, such as electrically active nerve cells, • 60 to 70 percent of the cells' energy requirement may be devoted to pumping Na+ out of the cell and • K+ into the cell. 9/28/2018 82Dr.Anu Priya J
  • 79.
    • The Na+-K+Pump Is Important For Controlling Cell Volume • One of the most important functions of the Na+-K+ pump is to control the volume of each cell. Without • function of this pump, most cells of the body would swell until they burst. The mechanism for controlling • the volume is as follows: Inside the cell are large numbers of proteins and other organic molecules that • cannot escape from the cell. Most of these are negatively charged and therefore attract large numbers • of potassium, sodium, and other positive ions as well. All these molecules and ions then cause osmosis • of water to the interior of the cell. Unless this is checked, the cell will swell indefinitely until it bursts. • The normal mechanism for preventing this is the Na+-K+ pump. Note again that this device pumps • three Na+ ions to the outside of the cell for every two K+ ions pumped to the interior. Also, the • Guyton & Hall: Textbook of Medical Physiology, 12e [Vish'aAlc] tive Transport' of Substances Through Membranes • 93 / 1921 • membrane is far less permeable to sodium ions than to potassium ions, so once the sodium ions are on • the outside, they have a strong tendency to stay there. Thus, this represents a net loss of ions out of • the cell, which initiates osmosis of water out of the cell as well. • If a cell begins to swell for any reason, this automatically activates the Na+-K+ pump, moving still more • ions to the exterior and carrying water with them. Therefore, the Na+-K+ pump performs a continual • surveillance role in maintaining normal cell volume. 9/28/2018 83Dr.Anu Priya J
  • 80.
    • Electrogenic Natureof the Na+-K+ Pump • page 53 • page 54 • The fact that the Na+-K+ pump moves three Na+ ions to the exterior for every two K+ ions to the • interior means that a net of one positive charge is moved from the interior of the cell to the exterior for • each cycle of the pump. This creates positivity outside the cell but leaves a deficit of positive ions • inside the cell; that is, it causes negativity on the inside. Therefore, the Na+-K+ pump is said to be • electrogenic because it creates an electrical potential across the cell membrane. As discussed in • Chapter 5, this electrical potential is a basic requirement in nerve and muscle fibers for transmitting • nerve and muscle signals. 9/28/2018 84Dr.Anu Priya J
  • 81.
    Primary Active Transportof Hydrogen Ions • At two places in the body, primary active transport of hydrogen ions is important: (1) in the gastric glands of the stomach and (2) in the late distal tubules and cortical collecting ducts of the kidneys. • In the gastric glands, the deep-lying parietal cells have the most potent primary active mechanism for transporting hydrogen ions of any part of the body. This is the basis for secreting hydrochloric acid in the stomach digestive secretions. At the secretory ends of the gastric gland parietal cells, the hydrogen ion concentration is increased as much as a millionfold and then released into the stomach along with chloride ions to form hydrochloric acid. • In the renal tubules are special intercalated cells in the late distal tubules and cortical collecting ducts that also transport hydrogen ions by primary active transport. In this case, large amounts of hydrogen ions are secreted from the blood into the urine for the purpose of eliminating excess hydrogen ions from the body fluids. The hydrogen ions can be secreted into the urine against a concentration gradient of about 900-fold. 9/28/2018 85Dr.Anu Priya J
  • 82.
    Secondary active transport •Energy utilised in the transport of one substance helps in the movement of the other substance. 9/28/2018 86Dr.Anu Priya J
  • 83.
    • Secondary ActiveTransport-Co-Transport • When sodium ions are transported out of cells by primary active transport, a large concentration gradient of sodium ions across the cell membrane usually develops-high concentration outside the cell and low concentration inside. • This gradient represents a storehouse of energy because the excess sodium outside the cell membrane is always attempting to diffuse to the interior. • Under appropriate conditions, this diffusion energy of sodium can pull other substances along with the sodium through the cell membrane. This phenomenon is called co-transport; it is one form of secondary active transport. • For sodium to pull another substance along with it, a coupling mechanism is required. This is achieved by means of still another carrier protein in the cell membrane. The carrier in this instance serves as an attachment point for both the sodium ion and the substance to be co-transported. • Once they both are attached, the energy gradient of the sodium ion causes both the sodium ion and the other substance to be transported together to the interior of the cell. 9/28/2018 87Dr.Anu Priya J
  • 84.

Editor's Notes

  • #11 Random movement until equilbm achvd
  • #29 Filtrn – oncotic press – mvt rltn bw tissue fluid n blood vessel ,,,,, tonicity – osmotic press mvt rltd btw cell and surrounding fluid
  • #67 Transfer of antibodies across placenta from maternal circulation to fetal circulation
  • #74  In each of these instances, the carrier protein penetrates the membrane and functions as an enzyme ATPase, having the same capability to cleave ATP as the ATPase of the sodium carrier protein.The difference is that this protein has a highly specific binding site for calcium instead of for sodium.