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  • 1. Body Fluids and Transport
  • 2. Water
    • Body fluid is composed primarily of water
    • Water is the solvent in which all solutes in the body are either dissolved or suspended
    • An average male has 60-63% of his body weight as water
    • An average female has 45-52%, due to extra body fat
    • Infants are 80% water, and this decreases as a child grows until about age 8.
  • 3. Key concepts involving water
    • Body water is contained in two major body compartments (intracellular fluid compartment and extracellular fluid compartment)
    • Fluid balance is maintained when input and output are equal
    • The primary source of intake is water ingestion (eating and drinking)
    • In addition, digestion and metabolism of carbohydrates, proteins, and fats provides another source of intake
  • 4. Key concepts involving water
  • 5. Compartments
    • Intracellular fluid (ICF) represents the fluid inside the cells and is the largest compartment (2/3 of body water)
    • Extracellular fluid (ECF) represents the fluid outside the cells and is 1/3 of total.
    • ECF is further divided into interstitial (ISF) and is the plasma.
  • 6. ECF divisions
    • ISF occupies the space between cells and consists of 15% of total body fluid or ¾ of ECF
    • Plasma is the fluid portion of the blood and is 5% of total body fluid or ¼ of ECF
  • 7. BODY FLUIDS Distribution of Body Fluids ICF ECF 40% TBW 20% TBW P IS 60-kg man TBW = 0.6 x 60 kg = 36 L ICF = 0.4 x 60 kg = 24 L ECF = 12 L 3L 9L
  • 8. Movement of molecule across cell membrane
  • 9.
    • The movement of molecules and ions both between cell organelles and the cytosol and between cytosol and extracellular fluid depends on the properties of these membranes
      • Impermeable membrane - membrane though which nothing can pass
      • Freely permeable membrane - any substance can pass through it
      • Selectively permeable membrane - permits free passage of some materials and restricts passage of others
    Membrane Transport
  • 10. Simple Diffusion
    • The movement of molecules from one location to another as a result of their random thermal motion is known as diffusion
    • Net movement of particles from area of high concentration to area of low concentration
  • 11. Membrane Permeability
    • Diffusion through lipid bilayer
      • Nonpolar, hydrophobic substances diffuse much more rapidly across plasma membrane
    • Diffusion of Ions through channel proteins
      • water and charged hydrophilic solutes diffuse through channel proteins; these are lipid insoluble substances
    • Cells control permeability by regulating number of channel proteins
  • 12. Major characteristics of diffusion pathways Yes No Chemical specificity Ions Nonpolar Typical molecules using pathway Yes No Use of integral membrane protein Through protein Channels Through lipid Bilayer
  • 13. Electric Forces and Ion Movement
    • Separation of electric charge across plasma membrane known as membrane potential
    • The direction of ion flux across membranes depend on:
    • Concentration difference
    • Electrical difference
    • These two driving forces known as electrochemical gardient
  • 14. Osmosis
    • The net diffusion of water across a membrane is called osmosis
    • Most plasma membrane have permeability to water.
    • A group of membrane protein known as aquaporins form channel through which water can diffuse
  • 15. Solutes
    • Substances dissolved in a solution (sugar in your tea)
    • The addition of solute to water lowers the concentration of water in the solution
    • The greater the solute concentration the lower the water concentration
    • It does not depend on chemical nature
    • A molecule that ionizes in solution decreases the water concentration in proportion to the number of ion formed.
  • 16. Osmolarity
    • The total concentration of a solution is known as osmolarity.
    • It determine the water concentration in the solution. Higher osmolarity lower water concentration.
    • Osmotic pressure is the pressure that must be applied to the solution to prevent net flow of water.
  • 17.
    • Isotonic : A solution containing 300 mOsmol/L of non penetrating solutes,
  • 18. Solutes
    • Substances dissolved in a solution (sugar in your tea)
    • These may be electrolytes or non-electrolytes
    • Electrolytes have an electrical charge when they are dissolved in water
    • Electrolytes that have a positive charge are called cations
    • Electrolytes with negative charge are anions
  • 19. Diffusion Summary
    • Diffusion is the movement of molecule from one location to another by random thermal motion
    • The net flux between the two compartments always proceed from higher to lower concentration
    • Diffusion equilibirum is reached when the two concentration become equal
  • 20.
    • Nonpolar molecule diffuse rapidly than do polar or ionized molecules
    • Mineral ions diffuse across membranes by passing through ion channels formed by integral proteins
    • Diffusion of ions across membrane depends on both concentration difference and the membrane potential.
    • The flux of ions across a membrane can be altered by opening and closing ion channels
    Diffusion Summary
  • 21. Osmosis Summary
    • Water crosses membranes by (1) diffusion through lipid by layer and (2) diffusing through protein channels in the membrane
    • 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.
  • 22.
    • Osmosis across membrane permeable to water but impermeable to solute leads to increase volume in the compartment that initially had higher osmolarity.
    • 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.
    Osmosis Summary
  • 23.  
  • 24. Osmolality
    • 1 osmol solute dissolved in each kg of water
  • 25. Permeable to water, Not permeable to solutes Presence of a membrane Impermeable to solute That leads to the volume Changes associated with Osmosis.
  • 26. Osmotic Pressure
    • The greater the osmolarity, the greater its osmotic pressure.
    • The lower the water concentration, the higher the osmotic pressure.
  • 27. Tonicity
    • Describes the behavior of a cell when it is placed in a solution
    • Depends not only on the number of particles in solution, but also on the NATURE of the solute
  • 28. Tonicity
    • Describes the behavior of a cell when it is placed in a solution
    • Depends not only on the number of particles in solution, but also on the NATURE of the solute
  • 29. Water diffuses in Water diffuses out
  • 30. -osmotic vs. -tonic
    • 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.
  • 31. Therapies Based on Two Basic Principles
    • Water moves rapidly across cell membranes: Osmolarities of ICF and ECF remain almost exactly equal
    • 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
  • 32. Transport, the big picture fig 4-15
  • 33. 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
  • 34. Non-mediated vs. mediated transport fig 4-9
  • 35. Primary active transport (Na + /K + ATPase pump) 3 Na + ’s out, 2 K + ’s in, 1 ATP hydrolyzed fig 4-11
  • 36. Primary active transport (Na + /K + ATPase pump) 3 Na + ’s out, 2 K + ’s in, 1 ATP hydrolyzed fig 4-11
  • 37. Primary active transport kinetics shows active transport shows carrier mediated
  • 38. Effect of Na + /K + ATPase pump fig 4-12
  • 39. Secondary active transport fig 4-13
  • 40. 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
  • 41. Sodium Reabsorption: Primary Active Transport
    • Sodium reabsorption is almost always by active transport
      • Na + enters the tubule cells at the luminal membrane
      • Is actively transported out of the tubules by a Na + -K + ATPase pump
    • From there it moves to peritubular capillaries due to:
      • Low hydrostatic pressure
      • High osmotic pressure of the blood
    • Na + reabsorption provides the energy and the means for reabsorbing most other solutes
  • 42. Electrolytes-Sodium
    • Major cation in ECF (positively charged)
    • Responsible for 90-95 % of extracellular osmotic pressure
    • Regulated by aldosterone and the kidneys
      • Increases sodium reabsorption in DCT of nephron
      • Also regulates K+ (secretion)
    • Normal serum concentration in ECF ranges from 135-146 mEq/L
  • 43. Sodium Functions
    • Sodium maintains ECF osmolality, ECF volume, and influences water distribution (where salt goes water follows)
    • 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
    • It also help aid the impulse transmission of nerve and muscle fibers
  • 44. Sodium Recycling: Recycling and Excretion
    • Ascending loop of Henle
      • H 2 O impermeable
      • Na + Active Transport
        • To ECF
        • Gradient
        • Diffuses to blood
    • Collecting Duct:
      • Aldosterone regulates
      • Na + recycled or excreted
  • 45.
    • Aldosterone: steroid H from adrenal cortex
      • Stimulates Na + uptake (& K + secretion)
      •  channel synthesis
    Mechanism of Na + Selective Reabsorption in Collecting Duct
  • 46. Mechanism of Na + Selective Reabsorption in Collecting Duct Figure 20-12: Aldosterone action in principal cells
  • 47. Imbalances
    • 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),
    • 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
  • 48. Artial Natruretic Peptide: Regulates Na + & H2O Excretion
    • Hormone from myocardial cells
    • Stimulates: hypothalamus, kidney, adrenal, & medulla
  • 49. Artial Natruretic Peptide: Regulates Na + & H 2 O Excretion Figure 20-15: Atrial natriuretic peptide
  • 50. Potassium Balance: Critical for Excitable Heart & Nervous Tissues
    • Hypokalemia – low [K + ] in ECF, Hyperkalemia - high [K + ]
    • Reabsorbed in Ascending Loop, secreted in Collecting duct
  • 51. Potassium Balance: Critical for Excitable Heart & Nervous Tissues Figure 20-4: Osmolarity changes as fluid flows through the nephron
  • 52. Potassium Balance: Critical for Excitable Heart & Nervous Tissues Figure 20-12: Aldosterone action in principal cells
  • 53.
    • Thirst & "salt craving", or avoidance behavior
    • Integrated circulatory & excretory reflexes
    Response to Dehydration & Osmolarity Imbalance
  • 54. Response to Dehydration & Osmolarity Imbalance
  • 55.
    • Acidosis:  plasma pH
      • Protein damage
      • CNS depression
    • Alkalosis:  plasma pH
      • Hyperexcitability
      • CNS & heart
    • Buffers: HCO 3 - & proteins
    • H + input: diet & metabolic
    • H + output: lungs & kidney
    Acid/Base Homeostasis: Overview
  • 56. Acid/Base Balance
    • Homeostasis of hydrogen ion content
    • Body fluids are classified as either acids or bases depending on H ion concentration
    • Acid is an H donor and elevates the hydrogen ion content of the solution to which it is added
    • Base is an H acceptor and can bind hydrogen ions
    • Concentration is expressed as pH
    • Normal pH of blood is 7.35-7.45 (alkaline)
    • pH below 6.8 or above 7.8 is incompatible with life
  • 57. Acids
    • During the process of cellular metabolism acids are continually being formed and excess hydrogen ions must be eliminated
    • There are two types of acids formed: volatile acids are excreted by the lungs and nonvolatile acids are excreted by the kidney
    • Volatile acids can be excreted from the body as gas. Carbonic acid produced by the hydration of carbon dioxide is a volatile acid
    • 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
  • 58. Non-volatile acids
    • Cannot be eliminated by the lungs and must be eliminated by the kidneys
    • All metabolic acids except carbolic are non-volatile acids
    • 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
  • 59. Regulation of pH
    • Three methods control pH
    • 1. chemical buffers-when Hydrogen is removed a buffer replaces it
    • 2. regulation of carbon dioxide by respiratory system
    • 3. regulation of plasma bicarbonate concentration by the kidneys-slower, second line of defense
  • 60. Chemical buffers
    • These are the first line of defense against changes in pH
    • Act within a fraction of a second for immediate defense against H+ shift
    • These are a mixture of 2 or more chemicals that minimize changes in pH
    • Convert strong acids into weak acids and strong bases into weak bases
  • 61. Buffers continued
    • Carbonic acid-bicarbonate system is most important extracellular buffer because it can be regulated by both lungs and kidneys
    • Carbonic acid/bicarbonate ratio is usually 1:20
    • CO 2 + H 2 O↔H 2 CO 3 ↔H + + HCO 3 -
    • Phosphates act as a buffer like the bicarbonate system does and protein buffers are the most abundant buffers in body cells and blood
  • 62. Regulation of pH through kidneys
    • Tubular secretion of H+ from convoluted tubules and collecting ducts so extra is excreted in urine
    • Helps regulate sulfuric acid and phosphoric acid, and other organic acids in body fluids as a result of metabolism
    • Diets high in protein generate more acid, so kidneys respond by secreting more hydrogen ion. (Atkins Diet)
    • In urine, hydrogen ion is buffered by phosphate and ammonia
  • 63. Acid/Base Homeostasis: Overview Figure 20-18: Hydrogen balance in the body
  • 64.
    • H + & NH 4 + secreted into lumen and excreted
    • HCO 3 - is reabsorbed
    Kidney Hydrogen Ion Balancing: Proximal Tubule
  • 65. Kidney Hydrogen Ion Balancing: Proximal Tubule Figure 20-21: Proximal tubule secretion and reabsorption of filtered HCO 3 -
  • 66.
    • Type A Intercalated cells excrete H + absorb HCO 3 -
    • Type B intercalated cells absorb H + secrete HCO 3 -
    Kidney Hydrogen Ion Balancing: Collecting Duct
  • 67. Kidney Hydrogen Ion Balancing: Collecting Duct Figure 20-22: Role of the intercalated cell in acidosis and alkalosis
  • 68. Ammonia
    • Ammonia (NH3) is a weak base produced in cells of renal tubule by removal of amine group from some amino acids (deamination)
    • It diffuses into the tubule and accepts hydrogen ions to become NH4+ which is trapped in the tubule and excreted
  • 69. Summary
    • Electrolyte balance depends on integration of circulatory, excretory and behavioral physiology
    • Water recycling and ECF/plasma balance depends on descending loop of Henle and vasopressin regulated collecting duct for conservation
    • Osmolarity depends on aldosterone and angiotensin pathway to regulate CNS & endocrine responses
    • Along with respiration, proximal tubule and collecting duct cells reabsorb or excrete H + & HCO 3 - to balance pH