mbbs ims msu


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mbbs ims msu

  1. 1. Mediated Transport System <ul><li>Passage of large molecule and some ions are mediated by integral membrane proteins known as transporters </li></ul><ul><li>Transport solute bind by specific site on the transporter </li></ul><ul><li>Change of the shape of transporter </li></ul><ul><li>Molecules can move in either direction. </li></ul><ul><li>The oscillation in conformation occur continuously. </li></ul>
  2. 2. <ul><li>Two types </li></ul><ul><li>Facilitated diffusion </li></ul><ul><li>Active transport </li></ul><ul><li>Facilitated diffusion uses transporter to move solute downhill from higher to lower concentration. </li></ul><ul><li>Active transporter uses energy to move solute uphill across the membrane </li></ul>Mediated Transport System
  3. 3. Diffusion Through the Plasma Membrane
  4. 4. Facilitated Diffusion <ul><li>From high to low concentration until the concentration on the two side of the membrane equal </li></ul><ul><li>No energy required </li></ul><ul><li>Facilitated diffusion such as those transport glucose </li></ul><ul><li>The transporter differs in their affinity of their binding sites for glucose </li></ul><ul><li>Their maximal rates of transport when saturated </li></ul><ul><li>Modulation of their transport activity by various chemical signals </li></ul>
  5. 5. <ul><li>When the concentration of x molecules outside the cell is low, the transport rate is low because it is limited by the number of molecules available to be transported. </li></ul><ul><li>When more molecules are present outside the cell, as long as enough carrier proteins are available, more molecules can be transported; thus, the transport rate increases. </li></ul><ul><li>The transport rate is limited by the number of carrier proteins and the rate at which each carrier protein can transport solutes. When the number of molecules outside the cell is so large that the carrier proteins are all occupied, the system is saturated and the transport rate cannot increase. </li></ul>Saturation of a Carrier Protein
  6. 6. Facilitated Diffusion <ul><li>Passive process, i.e. no ATP used </li></ul><ul><li>Solute binds to receptor on carrier protein </li></ul><ul><ul><li>Changes shape then releases solute on other side of membrane </li></ul></ul><ul><ul><li>Substance moved down its concentration gradient </li></ul></ul>
  7. 7. Active Transport <ul><li>Require energy to move substance uphill across the membrane </li></ul><ul><li>Require binding substance to the transporter </li></ul><ul><li>They referred as pumps </li></ul><ul><li>Exhibits specificity and saturation </li></ul>
  8. 8. <ul><li>Two means of energy flow: </li></ul><ul><li>The direct use of ATP in primary active transport </li></ul><ul><li>The use of ion concentration difference across membrane to drive the process secondary active transport </li></ul>Active Transport
  9. 9. Primary Active Transport <ul><li>Na,K-ATPase </li></ul><ul><li>Ca-ATPase </li></ul><ul><li>H-ATPase </li></ul><ul><li>H,K-ATPase </li></ul>
  10. 10. <ul><li>Na,K-ATPase: </li></ul><ul><li>Present in all plasma membrane </li></ul><ul><li>The pumping activity leads to distribution of high intracellular K and low intracellular Na relative to their extracellular concentration. </li></ul><ul><li>Ca-ATPase </li></ul><ul><li>Found in the plasma membrane and several organelle membranes </li></ul><ul><li>In plasma membrane the direction from cytosol to the extracellular fluid. In organelle membrane from cytosol into the organelle lumen </li></ul>Primary Active Transport
  11. 11. Primary active transport (Na + /K + ATPase pump) 3 Na + ’s out, 2 K + ’s in, 1 ATP hydrolyzed
  12. 12. Effect of Na + /K + ATPase pump fig 4-12
  13. 13. Sodium-Potassium Pump Extracellular fluid Binding of cytoplasmic Na+ to the pump protein stimulates phosphorylation by ATP. Phosphorylation causes the protein to change its shape. Concentration gradients of K + and Na + The shape change expels Na + to the outside, and extracellular K + binds. K + binding triggers release of the phosphate group. Loss of phosphate restores the original conformation of the pump protein. K + is released and Na + sites are ready to bind Na+ again; the cycle repeats.
  14. 14. <ul><li>H-ATPase </li></ul><ul><li>In the plasma membrane and several organelle membranes </li></ul><ul><li>Moves hydrogen ions out of the cell </li></ul><ul><li>H,K-ATPase </li></ul><ul><li>In the plasma membrane of acid secreting cells </li></ul><ul><li>It moves one hydrogen ion out of the cell and moves one potassium in. </li></ul>Primary Active Transport
  15. 15. Secondary Active Transport <ul><li>Uses ion concentration gradient across membrane as energy source </li></ul><ul><li>Having binding site for ion and actively transported solute </li></ul>
  16. 16. Secondary active transport fig 4-13
  17. 17. Secondary Active Transport <ul><ul><li>A sodium-potassium exchange pump maintains a concentration of Na that is higher outside the cell than inside. Active transport. </li></ul></ul><ul><ul><li>Na moves back into the cell by a carrier protein that also moves glucose. The concentration gradient for Na provides the energy required to move glucose against its concentration gradient. </li></ul></ul>
  18. 18. <ul><li>The movement of Na is always from high extracellular concentration into the cell where the concentration is lower </li></ul><ul><li>The movement of solute can be into the cell (same direction as Na) cotransport or out of the cell (opposite direction of Na movement) is called countertransport </li></ul>Secondary Active Transport
  19. 19. Composition of extracellular and intracellular fluids 4 0.2 Protein 4 0 ATP 10 110 Cl 1.5 1 Ca 150 4 K 15 145 Na Intracellular Con. mM Extracellular Con. mM
  20. 20. Major characteristics of mediated transport Yes Yes Yes Chemical specificity Polar: A.A, Glucose , some ions Ions Na, K ,Ca , H Polar: Glucose Typical molecules using pathway Yes Yes Yes Use of integral membrane protein Secondary Active Transport Primary Active Transport Facilitated Diffusion
  21. 21. Epithelial Transport <ul><li>Epithelial cells line hollow organ regulate absorption of substance </li></ul><ul><li>One surface faces a hollow refers to luminal membrane of the epithelium </li></ul><ul><li>The plasma membrane opposite surface refers to basolateral membrane </li></ul>
  22. 22. <ul><li>Two pathways: </li></ul><ul><li>Paracellular pathway: diffusion between the adjacent cell </li></ul><ul><li>Transcellular pathway: movement into the epithelial cell across either luminal </li></ul>Epithelial Transport
  23. 23. <ul><li>Paracellular is limited by the presence of tight junctions </li></ul><ul><li>Transcellular: movement of molecule occur via the pathways. </li></ul><ul><li>Transport characteristics of the luminal and basolateral membrane are not the same </li></ul>Epithelial Transport
  24. 24. Diffusion Summary <ul><li>Diffusion is the movement of molecule from one location to another by random thermal motion </li></ul><ul><li>The net flux between the two compartments always proceed from higher to lower concentration </li></ul><ul><li>Diffusion equilibirum is reached when the two concentration become equal </li></ul>
  25. 25. <ul><li>Nonpolar molecule diffuse rapidly than do polar or ionized molecules </li></ul><ul><li>Mineral ions diffuse across membranes by passing through ion channels formed by integral proteins </li></ul><ul><li>Diffusion of ions across membrane depends on both concentration difference and the membrane potential. </li></ul><ul><li>The flux of ions across a membrane can be altered by opening and closing ion channels </li></ul>Diffusion Summary
  26. 26. Osmosis Summary <ul><li>Water crosses membranes by (1) diffusion through lipid by layer and (2) diffusing through protein channels in the membrane </li></ul><ul><li>Osmosis is the diffusion of water from higher water concentration to lower water concentration. Osmolarity total solute concentration in the solution. The higher osmolarity of a solution the lower the water concentration. </li></ul>
  27. 27. <ul><li>Osmosis across membrane permeable to water but impermeable to solute leads to increase volume in the compartment that initially had higher osmolarity. </li></ul><ul><li>Application to a solution of sufficient pressure will prevent the osmotic flow of water into the solution from the compartment of pure water. This pressure is osmotic pressure. </li></ul>Osmosis Summary
  28. 28. Permeable to water, Not permeable to solutes Presence of a membrane Impermeable to solute That leads to the volume Changes associated with Osmosis.
  29. 29. Tonicity <ul><li>Describes the behavior of a cell when it is placed in a solution </li></ul><ul><li>Depends not only on the number of particles in solution, but also on the NATURE of the solute </li></ul>
  30. 30. Water diffuses in Water diffuses out
  31. 31. -osmotic vs. -tonic <ul><li>Example: 1L solution containing 300 mOsm of non-penetrating NaCl and 100 mOsm of urea, which can cross the membrane would have a total osmolarity of 400 mOsm and would be hyperosmotic. However, it would be an isotonic solution producing no change in the equilibrium volume of cells immersed in it. </li></ul>
  32. 32. Therapies Based on Two Basic Principles <ul><li>Water moves rapidly across cell membranes: Osmolarities of ICF and ECF remain almost exactly equal </li></ul><ul><li>Cell membranes are almost completely impermeable to many solutes: the number of osmoles in the ECF or ICF remains constant unless solutes are added or lost from the ECF compartment </li></ul>
  33. 33. Transport, the big picture fig 4-15
  34. 34. Facilitated diffusion (properties) Passive, carrier mediated Examples: glucose into most cells (not luminal membrane of kidney or intestine), urea, some amino acids Kinetics: shows: passive shows: carrier mediated
  35. 35. Non-mediated vs. mediated transport fig 4-9
  36. 36. Primary active transport (Na + /K + ATPase pump) 3 Na + ’s out, 2 K + ’s in, 1 ATP hydrolyzed fig 4-11
  37. 37. Primary active transport kinetics shows active transport shows carrier mediated
  38. 38. Secondary active transport properties Active (energy from ion gradient, usually Na + ) Carrier mediated Can be cotransport (symport) or countertransport (antiport) Examples (many): Na + /amino acids, Na + /glucose (luminal membrane kidney, GI tract), *Na + /H + kidney, *Ca ++ /3Na + muscle, *Cl - /HCO 3 - red cell. (* = countertransport) Kinetics see primary active transport graphs
  39. 39. Sodium Reabsorption: Primary Active Transport <ul><li>Sodium reabsorption is almost always by active transport </li></ul><ul><ul><li>Na + enters the tubule cells at the luminal membrane </li></ul></ul><ul><ul><li>Is actively transported out of the tubules by a Na + -K + ATPase pump </li></ul></ul><ul><li>From there it moves to peritubular capillaries due to: </li></ul><ul><ul><li>Low hydrostatic pressure </li></ul></ul><ul><ul><li>High osmotic pressure of the blood </li></ul></ul><ul><li>Na + reabsorption provides the energy and the means for reabsorbing most other solutes </li></ul>
  40. 40. Electrolytes-Sodium <ul><li>Major cation in ECF (positively charged) </li></ul><ul><li>Responsible for 90-95 % of extracellular osmotic pressure </li></ul><ul><li>Regulated by aldosterone and the kidneys </li></ul><ul><ul><li>Increases sodium reabsorption in DCT of nephron </li></ul></ul><ul><ul><li>Also regulates K+ (secretion) </li></ul></ul><ul><li>Normal serum concentration in ECF ranges from 135-146 mEq/L </li></ul>
  41. 41. Sodium Functions <ul><li>Sodium maintains ECF osmolality, ECF volume, and influences water distribution (where salt goes water follows) </li></ul><ul><li>It affects the concentration, secretion, and adsorption of potassium and chloride ions, and can combine with bicarbonate ions and chloride ions to help regulate acid/base balance </li></ul><ul><li>It also help aid the impulse transmission of nerve and muscle fibers </li></ul>
  42. 42. Sodium Recycling: Recycling and Excretion <ul><li>Ascending loop of Henle </li></ul><ul><ul><li>H 2 O impermeable </li></ul></ul><ul><ul><li>Na + Active Transport </li></ul></ul><ul><ul><ul><li>To ECF </li></ul></ul></ul><ul><ul><ul><li>Gradient </li></ul></ul></ul><ul><ul><ul><li>Diffuses to blood </li></ul></ul></ul><ul><li>Collecting Duct: </li></ul><ul><ul><li>Aldosterone regulates </li></ul></ul><ul><ul><li>Na + recycled or excreted </li></ul></ul>
  43. 43. <ul><li>Aldosterone: steroid H from adrenal cortex </li></ul><ul><ul><li>Stimulates Na + uptake (& K + secretion) </li></ul></ul><ul><ul><li> channel synthesis </li></ul></ul>Mechanism of Na + Selective Reabsorption in Collecting Duct
  44. 44. Mechanism of Na + Selective Reabsorption in Collecting Duct Figure 20-12: Aldosterone action in principal cells
  45. 45. Imbalances <ul><li>Hyponatremia (less than 130 mEq/L)-low sodium level-may cause seizures, headache, tachycardia, hypotension, cramps, muscle twitching, irritability, decreased body temp, nausea, vomiting, and possible coma (polyuria due to diabetes insipidis may be one cause), </li></ul><ul><li>Hypernatremia (more than 150 mEq/L) -high sodium level-usually indicates water deficit in ECF-symptoms include thirst, tachycardia, dry sticky tongue, disorientation, hallucination, lethargy, seizures, coma, hypotension, agitation, low fever </li></ul>
  46. 46. Artial Natruretic Peptide: Regulates Na + & H2O Excretion <ul><li>Hormone from myocardial cells </li></ul><ul><li>Stimulates: hypothalamus, kidney, adrenal, & medulla </li></ul>
  47. 47. Artial Natruretic Peptide: Regulates Na + & H 2 O Excretion Figure 20-15: Atrial natriuretic peptide
  48. 48. Potassium Balance: Critical for Excitable Heart & Nervous Tissues <ul><li>Hypokalemia – low [K + ] in ECF, Hyperkalemia - high [K + ] </li></ul><ul><li>Reabsorbed in Ascending Loop, secreted in Collecting duct </li></ul>
  49. 49. Potassium Balance: Critical for Excitable Heart & Nervous Tissues Figure 20-4: Osmolarity changes as fluid flows through the nephron
  50. 50. Potassium Balance: Critical for Excitable Heart & Nervous Tissues Figure 20-12: Aldosterone action in principal cells
  51. 51. <ul><li>Thirst & &quot;salt craving&quot;, or avoidance behavior </li></ul><ul><li>Integrated circulatory & excretory reflexes </li></ul>Response to Dehydration & Osmolarity Imbalance
  52. 52. Response to Dehydration & Osmolarity Imbalance
  53. 53. <ul><li>Acidosis:  plasma pH </li></ul><ul><ul><li>Protein damage </li></ul></ul><ul><ul><li>CNS depression </li></ul></ul><ul><li>Alkalosis:  plasma pH </li></ul><ul><ul><li>Hyperexcitability </li></ul></ul><ul><ul><li>CNS & heart </li></ul></ul><ul><li>Buffers: HCO 3 - & proteins </li></ul><ul><li>H + input: diet & metabolic </li></ul><ul><li>H + output: lungs & kidney </li></ul>Acid/Base Homeostasis: Overview
  54. 54. Acid/Base Balance <ul><li>Homeostasis of hydrogen ion content </li></ul><ul><li>Body fluids are classified as either acids or bases depending on H ion concentration </li></ul><ul><li>Acid is an H donor and elevates the hydrogen ion content of the solution to which it is added </li></ul><ul><li>Base is an H acceptor and can bind hydrogen ions </li></ul><ul><li>Concentration is expressed as pH </li></ul><ul><li>Normal pH of blood is 7.35-7.45 (alkaline) </li></ul><ul><li>pH below 6.8 or above 7.8 is incompatible with life </li></ul>
  55. 55. Acids <ul><li>During the process of cellular metabolism acids are continually being formed and excess hydrogen ions must be eliminated </li></ul><ul><li>There are two types of acids formed: volatile acids are excreted by the lungs and nonvolatile acids are excreted by the kidney </li></ul><ul><li>Volatile acids can be excreted from the body as gas. Carbonic acid produced by the hydration of carbon dioxide is a volatile acid </li></ul><ul><li>Normally carbon dioxide is excreted by the lungs as fast as metabolism produces it, so carbonic acid is not allowed to accumulate and alter pH </li></ul>
  56. 56. Non-volatile acids <ul><li>Cannot be eliminated by the lungs and must be eliminated by the kidneys </li></ul><ul><li>All metabolic acids except carbolic are non-volatile acids </li></ul><ul><li>These include sulfuric acid, phosphoric acid, lactic acid, ketoacids like acetoacetic acid and beta hydroxybutyric acid, and small amounts of other inorganic and organic acids </li></ul>
  57. 57. Regulation of pH <ul><li>Three methods control pH </li></ul><ul><li>1. chemical buffers-when Hydrogen is removed a buffer replaces it </li></ul><ul><li>2. regulation of carbon dioxide by respiratory system </li></ul><ul><li>3. regulation of plasma bicarbonate concentration by the kidneys-slower, second line of defense </li></ul>
  58. 58. Chemical buffers <ul><li>These are the first line of defense against changes in pH </li></ul><ul><li>Act within a fraction of a second for immediate defense against H+ shift </li></ul><ul><li>These are a mixture of 2 or more chemicals that minimize changes in pH </li></ul><ul><li>Convert strong acids into weak acids and strong bases into weak bases </li></ul>
  59. 59. Buffers continued <ul><li>Carbonic acid-bicarbonate system is most important extracellular buffer because it can be regulated by both lungs and kidneys </li></ul><ul><li>Carbonic acid/bicarbonate ratio is usually 1:20 </li></ul><ul><li>CO 2 + H 2 O↔H 2 CO 3 ↔H + + HCO 3 - </li></ul><ul><li>Phosphates act as a buffer like the bicarbonate system does and protein buffers are the most abundant buffers in body cells and blood </li></ul>
  60. 60. Regulation of pH through kidneys <ul><li>Tubular secretion of H+ from convoluted tubules and collecting ducts so extra is excreted in urine </li></ul><ul><li>Helps regulate sulfuric acid and phosphoric acid, and other organic acids in body fluids as a result of metabolism </li></ul><ul><li>Diets high in protein generate more acid, so kidneys respond by secreting more hydrogen ion. (Atkins Diet) </li></ul><ul><li>In urine, hydrogen ion is buffered by phosphate and ammonia </li></ul>
  61. 61. Acid/Base Homeostasis: Overview Figure 20-18: Hydrogen balance in the body
  62. 62. <ul><li>H + & NH 4 + secreted into lumen and excreted </li></ul><ul><li>HCO 3 - is reabsorbed </li></ul>Kidney Hydrogen Ion Balancing: Proximal Tubule
  63. 63. Kidney Hydrogen Ion Balancing: Proximal Tubule Figure 20-21: Proximal tubule secretion and reabsorption of filtered HCO 3 -
  64. 64. <ul><li>Type A Intercalated cells excrete H + absorb HCO 3 - </li></ul><ul><li>Type B intercalated cells absorb H + secrete HCO 3 - </li></ul>Kidney Hydrogen Ion Balancing: Collecting Duct
  65. 65. Kidney Hydrogen Ion Balancing: Collecting Duct Figure 20-22: Role of the intercalated cell in acidosis and alkalosis
  66. 66. Ammonia <ul><li>Ammonia (NH3) is a weak base produced in cells of renal tubule by removal of amine group from some amino acids (deamination) </li></ul><ul><li>It diffuses into the tubule and accepts hydrogen ions to become NH4+ which is trapped in the tubule and excreted </li></ul>
  67. 67. Summary <ul><li>Electrolyte balance depends on integration of circulatory, excretory and behavioral physiology </li></ul><ul><li>Water recycling and ECF/plasma balance depends on descending loop of Henle and vasopressin regulated collecting duct for conservation </li></ul><ul><li>Osmolarity depends on aldosterone and angiotensin pathway to regulate CNS & endocrine responses </li></ul><ul><li>Along with respiration, proximal tubule and collecting duct cells reabsorb or excrete H + & HCO 3 - to balance pH </li></ul>