1. General Principles of Pathophysiology n The Cellular Environment n Fluids & Electrolytes n Acid-base Balance & Maintenance n The Cellular Environment n Fluids & Electrolytes n Acid-base Balance & Maintenance

2. TopicsTopics n Describe the distribution of water in the body n Discuss common physiologic electrolytes n Review mechanisms of transport –osmosis, diffusion, etc n Discuss hemostasis & blood types n Discuss concepts of acid-base maintenance n Describe the distribution of water in the body n Discuss common physiologic electrolytes n Review mechanisms of transport –osmosis, diffusion, etc n Discuss hemostasis & blood types n Discuss concepts of acid-base maintenance

3. Distribution of Water n Total Body Weight/ Total Body Water n Intracellular - ICF (45%/75%) n Extracellular - ECF (15%/25%) –Intravascular (4.5%/7.5%) –Interstitial (10.5%/17.5%) n Total Body Weight/ Total Body Water n Intracellular - ICF (45%/75%) n Extracellular - ECF (15%/25%) –Intravascular (4.5%/7.5%) –Interstitial (10.5%/17.5%)

4. Intra-cellular45% 31.5 kg Intra-cellular45% Interstitial 10.5 % 7.35 kg Interstitial 10.5 % 7.35 kg Intra-vascular4.5% 3.15 kg Intra-vascular4.5% Total Body Weight Fluid Distribution Extracellular Cell Membrane Capillary Membrane

5. Fluid Distribution Intra-cellular75% 31.5 L Intra-cellular75% Interstitial 17.5 % 7.35 L Interstitial 17.5 % 7.35 L Intra-vascular7.5% 3.15 L Intra-vascular7.5% Total Body Water Extracellular Cell Membrane Capillary Membrane

6. Total Body Weight

7. Total Body Water

8. EdemaEdema n Fluid accumulation in the interstitial compartment n Causes: –Lymphatic ‘leakage’ –Excessive hydrostatic pressure –Inadequate osmotic pressure n Fluid accumulation in the interstitial compartment n Causes: –Lymphatic ‘leakage’ –Excessive hydrostatic pressure –Inadequate osmotic pressure

9. Fluid Intake Water from beverages: 1600 ml (64%) Water from food: 700 ml (28%) Water from metabolism: 200 ml (8%)

10. Fluid Output Water from skin: 550 ml (25%) Water from feces: 150 ml (5%) Water from lungs: 300 ml (11%) Water from urine: 1500 ml (59%)

11. Osmosis versus Diffusion n Osmosis is the net movement of water from an area of LOW solute concentration to an area of HIGHER solute concentration across a semi- permeable membrane. n diffusion of water –in terms of [water] n Osmosis is the net movement of water from an area of LOW solute concentration to an area of HIGHER solute concentration across a semi- permeable membrane. n diffusion of water –in terms of [water] n Diffusion is the net movement of solutes from an area of HIGH solute concentration to an area of LOWER solute concentration.

12. Silly definition stuff n Osmolarity = osmoles/L of solution n Osmolality = osmoles/kg of solution Where an osmole is 1 mole (6.02 x 10 23 particles) The bottom line? Use them synonymously! The bottom line? Use them synonymously!

13. TonicityTonicity n Isotonic n Hypertonic n Hypotonic n Isotonic n Hypertonic n Hypotonic

14. Isotonic Solutions n Same solute concentration as RBC n If injected into vein: no net movement of fluid n Example: 0.9% sodium chloride solution –aka Normal Saline n Same solute concentration as RBC n If injected into vein: no net movement of fluid n Example: 0.9% sodium chloride solution –aka Normal Saline

15. Hypertonic Solutions n Higher solute concentration than RBC n If injected into vein: –Fluid moves INTO veins n Higher solute concentration than RBC n If injected into vein: –Fluid moves INTO veins

16. Hypotonic Solutions n Lower solute concentration than RBC n If injected into vein: –Fluid moves OUT of veins n Lower solute concentration than RBC n If injected into vein: –Fluid moves OUT of veins

17. Affects of Hypotonic Solution on Cell Cell Swelling Cell Swollen Cell RupturedCell n The [solute] outside the cell is lower than inside. n Water moves from low [solute] to high [solute]. n The cell swells and eventually bursts! n The [solute] outside the cell is lower than inside. n Water moves from low [solute] to high [solute]. n The cell swells and eventually bursts!

18. Affects of Hypertonic Solution on Cell Cell n The [solute] outside the cell is higher than inside. n Water moves from low [solute] to high [solute]. n The cell shrinks! n The [solute] outside the cell is higher than inside. n Water moves from low [solute] to high [solute]. n The cell shrinks! Shrinking Cell Shrunken Cell

19. n Infusion of hypertonic solution into veins n No fluid movement n Fluid movement into veins n Fluid movement out of veins n Infusion of isotonic solution into veins n Infusion of hypotonic solution into veins

20. Ion Distribution 0 50 100 150 50 100 150 mEq/L Na + K+K+K+K+ Cl - PO 4 - Protein - Cations Anions Extracellular Intracellular

21. Example of Role of Electrolytes n Nervous System –Propagation of Action Potential n Cardiovascular System –Cardiac conduction & contraction n Nervous System –Propagation of Action Potential n Cardiovascular System –Cardiac conduction & contraction

22. Cardiac Conduction / Contraction

23. Composition of Blood n 8% of total body weight n Plasma: 55% –Water: 90% –Solutes: 10% n Formed elements: 45% –Platelets –Erythrocytes n 8% of total body weight n Plasma: 55% –Water: 90% –Solutes: 10% n Formed elements: 45% –Platelets –Erythrocytes

24. HematrocritHematrocrit n % of RBC in blood n Normal: –37% - 47% (Female) –40% - 54% (Male) n % of RBC in blood n Normal: –37% - 47% (Female) –40% - 54% (Male)

25. Blood Components n Plasma: liquid portion of blood n Contains Proteins –Albumin (60%) contribute to osmotic pressure –Globulin (36%): lipid transport and antibodies –Fibrinogen (4%): blood clotting n Plasma: liquid portion of blood n Contains Proteins –Albumin (60%) contribute to osmotic pressure –Globulin (36%): lipid transport and antibodies –Fibrinogen (4%): blood clotting

26. Blood Components n Formed Elements –Erythrocytes –Leukocytes –Thrombocytes n Formed Elements –Erythrocytes –Leukocytes –Thrombocytes

27. ErythrocytesErythrocytes n ‘biconcave’ disc n 7-8 mcm diameter n Packed with hemoglobin n 4.5 - 6 million RBC/mm 3 (males) n Anucleate n 120 day life span n 2 million replaced per second! n ‘biconcave’ disc n 7-8 mcm diameter n Packed with hemoglobin n 4.5 - 6 million RBC/mm 3 (males) n Anucleate n 120 day life span n 2 million replaced per second!

28. LeukocytesLeukocytes n Most work done in tissues n 5,000 - 6,000/mm 3 –Neutrophils (60-70%) –Basophils (Mast Cells) (<1%) –Eosinophils (2-4%) –Lymphocytes (20-25%) –Monocytes (Macrophages) (3-8%) n Most work done in tissues n 5,000 - 6,000/mm 3 –Neutrophils (60-70%) –Basophils (Mast Cells) (<1%) –Eosinophils (2-4%) –Lymphocytes (20-25%) –Monocytes (Macrophages) (3-8%)

29. ThrombocytesThrombocytes n Platelets n Cell fragments n 250,000 - 500,000/mm 3 n Form platelet plugs n Platelets n Cell fragments n 250,000 - 500,000/mm 3 n Form platelet plugs

30. HemostasisHemostasis n The stoppage of bleeding. n Three methods –Vascular constriction –Platelet plug formation –Coagulation n The stoppage of bleeding. n Three methods –Vascular constriction –Platelet plug formation –Coagulation

31. CoagulationCoagulation n Formation of blood clots n Prothrombin activator n Prothrombin  Thrombin n Fibrinogen  Fibrin n Clot retraction n Formation of blood clots n Prothrombin activator n Prothrombin  Thrombin n Fibrinogen  Fibrin n Clot retraction

32. CoagulationCoagulation ProthrombinActivatorProthrombinActivator ProthrombinProthrombin ThrombinThrombin FibrinogenFibrinogen FibrinFibrin ClotClot

33. FibrinolysisFibrinolysis n Plasminogen n tissue plasminogen activator (tPA) n Plasmin n Plasminogen n tissue plasminogen activator (tPA) n Plasmin

34. Blood Types n Agglutinogens (Blood Antigens) n Agglutinins (Blood Antibodies) n Agglutination (RBC clumping) n ABO n Rh Antigens n Agglutinogens (Blood Antigens) n Agglutinins (Blood Antibodies) n Agglutination (RBC clumping) n ABO n Rh Antigens

35. Type A Blood

36. Type B Blood

37. Type AB Blood

38. Type O Blood

39. Rh Antigens

40. Bottom line of Acid-Base n Regulation of [H+] –normally about 1/3.5 million that of [Na + ] –0.00004 mEq/L (4 x 10 -8 Eq/L) n Dependent upon –Kidneys –Chemical Buffers n Precise regulation necessary for peak enzyme activity n Regulation of [H+] –normally about 1/3.5 million that of [Na + ] –0.00004 mEq/L (4 x 10 -8 Eq/L) n Dependent upon –Kidneys –Chemical Buffers n Precise regulation necessary for peak enzyme activity

41. pH Effects on Enzyme Activity pH Enzyme Activity  activity Peak Activity  activity

42. Acid Base n Acids release H + –example: HCl -> H + + Cl - n Bases absorb H + –example: HCO 3 - + H + -> H 2 CO 3 n Acids release H + –example: HCl -> H + + Cl - n Bases absorb H + –example: HCO 3 - + H + -> H 2 CO 3

43. pH is logarithmic n pH = log 1/[H + ] n = - log [H + ] n = - log 0.00000004 Eq/L n pH = 7.4 n Think of pH as ‘power of [H + ] n pH = log 1/[H + ] n = - log [H + ] n = - log 0.00000004 Eq/L n pH = 7.4 n Think of pH as ‘power of [H + ]

44. pH is Logarithmic pH is inversely related to [H+] pH is inversely related to [H+] Small  pH mean large  [H + ] Small  pH mean large  [H + ] as [H+]  pH  as [H+]  pH  as [H+]  pH  as [H+]  pH  & pH 7.4 = 0.00000004 pH 7.1 = 0.00000008 (it doubled!) pH 7.4 = 0.00000004 pH 7.1 = 0.00000008 (it doubled!)

45. Buffers Resist pH Changes n Weak acid & conjugate base pair n H 2 CO 3  HCO 3 - + H + n Conjugate Acid  conjugate base + acid n Weak acid & conjugate base pair n H 2 CO 3  HCO 3 - + H + n Conjugate Acid  conjugate base + acid

46. Henderson-Hasselbalch Equation n pH = pK a + log [base]/[acid] –Ex: = 6.1 + log 20/1 = 6.1 + 1.3 = 7.4 n Key ratio is base: acid –HCO 3 - : CO 2 (standing in for H 2 CO 3 ) n pH = pK a + log [base]/[acid] –Ex: = 6.1 + log 20/1 = 6.1 + 1.3 = 7.4 n Key ratio is base: acid –HCO 3 - : CO 2 (standing in for H 2 CO 3 )

47. pH Scale n 0 : Hydrochloric Acid n 1: Gastric Acid n 2: Lemon Juice n 3: Vinegar, Beer n 4: Tomatoes n 5: Black Coffee n 6: Urine n 6.5: Saliva n 0 : Hydrochloric Acid n 1: Gastric Acid n 2: Lemon Juice n 3: Vinegar, Beer n 4: Tomatoes n 5: Black Coffee n 6: Urine n 6.5: Saliva n 7: Blood n 8: Sea Water n 9: Baking Soda n 10: Great Salt Lake n 11: Ammonia n 12: Bicarbonate n 13: Oven Cleaner n 14: NaOH

48. Acid Base Compensation n Buffer System n Respiratory System n Renal System n Buffer System n Respiratory System n Renal System

49. Buffer System n Immediate n CO 2 + H 2 0  H 2 CO 3  H + + HCO 3 - n Equilibrium: 20 HCO 3 - to 1 CO 2 (H 2 CO 3 ) n Excessive CO 2  acidosis n Excessive HCO 3 -  alkalosis n Immediate n CO 2 + H 2 0  H 2 CO 3  H + + HCO 3 - n Equilibrium: 20 HCO 3 - to 1 CO 2 (H 2 CO 3 ) n Excessive CO 2  acidosis n Excessive HCO 3 -  alkalosis Simplified: CO 2  H + Simplified: CO 2  H +

50. Question...Question... Is the average pH of the blood lower in: a) arteries b) veins Is the average pH of the blood lower in: a) arteries b) veins Veins!Why? Because veins pick up the byproducts of cellular metabolism, including… CO 2 ! Because veins pick up the byproducts of cellular metabolism, including… CO 2 !

51. Respiratory System n Minutes n CO 2  H + n Respiration  : CO 2  : H +  n Respiration  : CO 2  : H +  n Minutes n CO 2  H + n Respiration  : CO 2  : H +  n Respiration  : CO 2  : H + 

52. Renal System n Hours to days n Recovery of Bicarbonate n Excretion of H + n Excretion of ammonium n Hours to days n Recovery of Bicarbonate n Excretion of H + n Excretion of ammonium

53. DisordersDisorders n Respiratory Acidosis n Respiratory Alkalosis n Metabolic Acidosis n Metabolic Alkalosis n Respiratory Acidosis n Respiratory Alkalosis n Metabolic Acidosis n Metabolic Alkalosis

54. Respiratory Acidosis n  CO 2 + H 2 0   H 2 CO 3   H + + HCO 3 Simplified:  CO 2   H + Simplified:  CO 2   H +

55. Respiratory Alkalosis n  CO 2 + H 2 0   H 2 CO 3   H + + HCO 3 Simplified:  CO 2   H + Simplified:  CO 2   H +

56. Metabolic Acidosis n  H + + HCO 3   H 2 CO 3  H 2 0 +  CO 2 Simplified: Producing too much H + Simplified: Producing too much H +

57. Metabolic Alkalosis n  H + + HCO 3   H 2 CO 3  H 2 0 +  CO 2 Simplified: Too much HCO 3 Simplified: Too much HCO 3

58. Normal Values n pH: 7.35 - 7.45 n PCO 2 : 35 - 45 n pH: 7.35 - 7.45 n PCO 2 : 35 - 45

59. Abnormal Values

60. All Roads Lead to Rome! Respiratory Opposes Metabolic Equals (or doesn’t oppose) Metabolic Equals (or doesn’t oppose)

61. Example:Example: n pH = 7.25 n PCO 2 = 60 n pH = 7.25 n PCO 2 = 60 RespiratoryAcidosis!RespiratoryAcidosis!

62. Example:Example: n pH = 7.50 n PCO 2 = 35 n pH = 7.50 n PCO 2 = 35 MetabolicAlkalosis!MetabolicAlkalosis!

63. Example:Example: n pH = 7.60 n PCO 2 = 20 n pH = 7.60 n PCO 2 = 20 RespiratoryAlkalosis!RespiratoryAlkalosis!

64. Example:Example: n pH = 7.28 n PCO 2 = 38 n pH = 7.28 n PCO 2 = 38 MetabolicAcidosis!MetabolicAcidosis!

65. ResourcesResources n A Continuing Education article on Acid- Base disturbances is available on our web site at: n http://www.templejc.edu/ems/resource.htm n A great online tutorial at: n http://www.tmc.tulane.edu/departments/anesthesi ology/acid/acid.html n A Continuing Education article on Acid- Base disturbances is available on our web site at: n http://www.templejc.edu/ems/resource.htm n A great online tutorial at: n http://www.tmc.tulane.edu/departments/anesthesi ology/acid/acid.html