mbbs ims msu

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mbbs ims msu

  1. 1. Osmosis <ul><li>The net diffusion of water across a membrane is called osmosis </li></ul><ul><li>Most plasma membrane have permeability to water. </li></ul><ul><li>A group of membrane protein known as aquaporins form channel through which water can diffuse </li></ul>
  2. 2. Osmolarity <ul><li>The total concentration of a solution is known as osmolarity. </li></ul><ul><li>It determine the water concentration in the solution. Higher osmolarity lower water concentration. </li></ul><ul><li>Osmotic pressure is the pressure that must be applied to the solution to prevent net flow of water. </li></ul>
  3. 3. Extracellular Osmolarity and Cell Volume <ul><li>Extracellular and intracellular contains water and the cells surrounded by membrane that is permeable to water </li></ul><ul><li>85% extracellular solute are sodium and chloride </li></ul><ul><li>Plasma membrane contain Na,K-ATPase pumps that moves Na ions out of the cell </li></ul><ul><li>Cl ions move out of cell by membrane potentials </li></ul><ul><li>Inside the cell K ions </li></ul>
  4. 4. <ul><li>The osmolarity of extracellular fluid is 300 mOsm </li></ul><ul><li>At equilibrium the osmolarities of intracellular and extracellular is same </li></ul><ul><li>Changes in extracellular osmolarity can cause cells to shrink or swell </li></ul>Extracellular Osmolarity and Cell Volume
  5. 5. <ul><li>Isotonic : having osmolarity of 300 mOsm same concentration of nonpenetrating solutes </li></ul><ul><li>Hypotonic : Solution containing less than 300 mOsm of nonpenetrating solutes cause cell swell </li></ul><ul><li>Hypertonic solution containing greater than 300 mOsm of nonpenetrating solutes cause cell to shrink </li></ul>Extracellular Osmolarity and Cell Volume
  6. 6. Effects of Tonicity on RBCs Hypotonic, isotonic and hypertonic solutions affect the fluid volume of a red blood cell. Notice the crenated and swollen cells.
  7. 7. <ul><li>Isoosmotic, hyperosmotic and hypoosmotic denotes osmolarity of a solution without regard to whether the solute is penetrating nonpenetratin </li></ul>Extracellular Osmolarity and Cell Volume
  8. 8. <ul><li>Isoosmotic : A solution containing 300 mOsmol/L of solute, regardless of its composition of membrane penetrating and non penetrating solutes </li></ul><ul><li>Hyper osmotic : A solution containing greater than 300 mOsmol/L solute </li></ul><ul><li>Hypo osmotic : A solution containing less than 300 mOsmol/L. </li></ul>Extracellular Osmolarity and Cell Volume
  9. 9. Endocytosis and Excocytosis <ul><li>Transport large particles or fluid droplets through membrane in vesicles </li></ul><ul><ul><li>uses ATP </li></ul></ul><ul><li>Exocytosis –transport out of cell </li></ul><ul><li>Endocytosis –transport into cell </li></ul><ul><ul><li>phagocytosis – engulfing large particles </li></ul></ul><ul><ul><li>pinocytosis – taking in fluid droplets </li></ul></ul><ul><ul><li>receptor mediated endocytosis – taking in specific molecules bound to receptors </li></ul></ul>
  10. 10. Endocytosis <ul><li>Packaging of extracellular materials in vesicles at the cell surface </li></ul><ul><li>Requires energy in the form of ATP </li></ul><ul><li>Three major types </li></ul><ul><ul><ul><li>Receptor-mediated endocytosis </li></ul></ul></ul><ul><ul><ul><li>Pinocytosis </li></ul></ul></ul><ul><ul><ul><li>Phagocytosis </li></ul></ul></ul>
  11. 11. Receptor Mediated Endocytosis <ul><li>A selective process </li></ul><ul><li>Involves formation of vesicles at surface of membrane </li></ul><ul><ul><li>Vesicles contain receptors on their membrane </li></ul></ul><ul><li>Clathrin-coated vesicle in cytoplasm </li></ul>
  12. 12. Receptor Mediated Endocytosis
  13. 13. Pinocytosis or “Cell-Drinking” <ul><li>Taking in droplets of ECF </li></ul><ul><ul><li>occurs in all human cells </li></ul></ul><ul><li>Not as selective as ‘receptor-mediated endocytosis’ </li></ul>
  14. 14. Phagocytosis or “Cell-Eating”
  15. 15. Exocytosis <ul><li>Two functions </li></ul><ul><li>It provides a way to replace portion of plasma membrane </li></ul><ul><li>It provides a route by which membrane impermeable molecules to release into extracellular fluids </li></ul>
  16. 16. Vesicular Transport: Exocytosis
  17. 17. Solutes <ul><li>Substances dissolved in a solution (sugar in your tea) </li></ul><ul><li>These may be electrolytes or non-electrolytes </li></ul><ul><li>Electrolytes have an electrical charge when they are dissolved in water </li></ul><ul><li>Electrolytes that have a positive charge are called cations </li></ul><ul><li>Electrolytes with negative charge are anions </li></ul>
  18. 18. 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>
  19. 19. <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
  20. 20. 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>
  21. 21. <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
  22. 23. Osmolality <ul><li>1 osmol solute dissolved in each kg of water </li></ul>
  23. 24. Permeable to water, Not permeable to solutes Presence of a membrane Impermeable to solute That leads to the volume Changes associated with Osmosis.
  24. 25. Osmotic Pressure <ul><li>The greater the osmolarity, the greater its osmotic pressure. </li></ul><ul><li>The lower the water concentration, the higher the osmotic pressure. </li></ul>
  25. 26. 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>
  26. 27. 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>
  27. 28. Water diffuses in Water diffuses out
  28. 29. -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>
  29. 30. 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>
  30. 31. Transport, the big picture fig 4-15
  31. 32. 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
  32. 33. Non-mediated vs. mediated transport fig 4-9
  33. 34. Primary active transport (Na + /K + ATPase pump) 3 Na + ’s out, 2 K + ’s in, 1 ATP hydrolyzed fig 4-11
  34. 35. Primary active transport (Na + /K + ATPase pump) 3 Na + ’s out, 2 K + ’s in, 1 ATP hydrolyzed fig 4-11
  35. 36. Primary active transport kinetics shows active transport shows carrier mediated
  36. 37. Effect of Na + /K + ATPase pump fig 4-12
  37. 38. Secondary active transport fig 4-13
  38. 39. 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. 40. 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. 41. 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. 42. 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. 43. 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. 44. <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. 45. Mechanism of Na + Selective Reabsorption in Collecting Duct Figure 20-12: Aldosterone action in principal cells
  45. 46. 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. 47. 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. 48. Artial Natruretic Peptide: Regulates Na + & H 2 O Excretion Figure 20-15: Atrial natriuretic peptide
  48. 49. 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. 50. Potassium Balance: Critical for Excitable Heart & Nervous Tissues Figure 20-4: Osmolarity changes as fluid flows through the nephron
  50. 51. Potassium Balance: Critical for Excitable Heart & Nervous Tissues Figure 20-12: Aldosterone action in principal cells
  51. 52. <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. 53. Response to Dehydration & Osmolarity Imbalance
  53. 54. <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. 55. 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. 56. 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. 57. 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. 58. 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. 59. 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. 60. 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. 61. 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. 62. Acid/Base Homeostasis: Overview Figure 20-18: Hydrogen balance in the body
  62. 63. <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. 64. Kidney Hydrogen Ion Balancing: Proximal Tubule Figure 20-21: Proximal tubule secretion and reabsorption of filtered HCO 3 -
  64. 65. <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. 66. Kidney Hydrogen Ion Balancing: Collecting Duct Figure 20-22: Role of the intercalated cell in acidosis and alkalosis
  66. 67. 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. 68. 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>

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