1. General Principles of Pathophysiology Energy Metabolism PerfusionShock PerfusionShock

2. TopicsTopics nDefine shock in terms of cellular function nReview the requirements for adequate cellular perfusion (Fick principle) nReview the mechanisms for starling’s law  Preload vs. afterload  Muscle contraction nDefine shock in terms of cellular function nReview the requirements for adequate cellular perfusion (Fick principle) nReview the mechanisms for starling’s law  Preload vs. afterload  Muscle contraction

3. Topics Continued nDiscuss the mechanisms for oxygen transport  oxyhemoglobin dissociation curve nDefine the stages of shock nDescribe different causes of shock nDefine multiple organ dysfunction syndrome nDiscuss the mechanisms for oxygen transport  oxyhemoglobin dissociation curve nDefine the stages of shock nDescribe different causes of shock nDefine multiple organ dysfunction syndrome

4. Shock Defined nInadequate tissue perfusion nAnaerobic metabolism nInadequate tissue perfusion nAnaerobic metabolism Final Common Pathway!

5. Aerobic Metabolism 6 O 2 GLUCOSE METABOLISM 6 CO 2 6 H 2 O 36 ATP HEAT (417 kcal)

6. Anaerobic Metabolism GLUCOSEMETABOLISM 2 LACTIC ACID 2 ATP HEAT (32 kcal)

7. Anaerobic? So What? InadequateCellularOxygenationInadequateCellularOxygenation AnaerobicMetabolismAnaerobicMetabolism MetabolicFailureMetabolicFailureMetabolicAcidosisMetabolicAcidosis InadequateEnergyProductionInadequateEnergyProduction Lactic Acid Production Production Cell Death!

8. Homeostasis is maintenance of balance nRequires proper functioning systems  Cardiovascular  Respiratory  Renal nRequires proper functioning systems  Cardiovascular  Respiratory  Renal

9. Physiology of Perfusion nDependant on 3 components of circulatory system  Pump  Fluid  Container nDependant on 3 components of circulatory system  Pump  Fluid  Container

10. Factors Affecting The Pump nPreload nContractile force  Frank-starling mechanism nAfterload nPreload nContractile force  Frank-starling mechanism nAfterload

11. Muscle Anatomy

12. Contraction: Sliding Filaments image from: http://www.accessexcellence.com/AB/GG/muscle_Contract.html

13. What Is Blood Pressure? BP = Cardiac Output X Systemic Vascular Resistance BP = Cardiac Output X Systemic Vascular Resistance CO = Stroke Volume X Heart Rate CO = Stroke Volume X Heart Rate

14. What Affects Blood Pressure? nANS balance nContractility  Preload  Starling’s law nAfterload nANS balance nContractility  Preload  Starling’s law nAfterload

15. Autonomic Nervous System Review… Quiz Time! Yeah!

16. JeopardyJeopardy Controls vegetative functions,exits the CNS at high in the neck and low in the back. What is the parasympathetic nervous system? What is the parasympathetic nervous system?

17. JeopardyJeopardy The chief neurotransmitter of the sympathetic nervous system. What is Norepinephrine? Norepinephrine?

18. JeopardyJeopardy The ‘cutesy’ name for the parasympathetic nervous system. What is ‘Feed or Breed’? What is ‘Feed or Breed’?

19. JeopardyJeopardy Two types of parasympathetic receptors. What is nicotinic (NMJ) and muscarinic (organs)? What is nicotinic (NMJ) and muscarinic (organs)?

20. JeopardyJeopardy Two types classes of sympathetic receptors. What is alpha and beta? What is alpha and beta?

21. JeopardyJeopardy The ‘cutesy name’ for the sympathetic nervous system. What is ‘fight or flight’? What is ‘fight or flight’?

22. JeopardyJeopardy Stimulation of this receptor causes an increase in peripheral vasoconstriction. What is alpha 1?

23. JeopardyJeopardy Stimulation of this receptor causes an increase in myocardial contractility. What is beta 1?

24. JeopardyJeopardy Stimulation of this receptor causes an increase in bronchodilation. What is beta 2?

25. JeopardyJeopardy Stimulation of this receptor causes a decrease in the sympathetic activation. What is alpha 2?

26. JeopardyJeopardy Two types of parasympathetic receptors. What is nicotinic (NMJ) and muscarinic (organs). What is nicotinic (NMJ) and muscarinic (organs).

27. Changes in Afterload and Preload n  Peripheral vasoconstriction…  n  peripheral vascular resistance… n  afterload… n  blood pressure.

28. Changes in Afterload and Preload n  Peripheral vasodilation…      n  peripheral vascular resistance… n  afterload… n  blood pressure.

29. Changes in Afterload and Preload n  fluid volume…  n  preload… n  contractility (Starling’s Law)… n  cardiac output. n  blood pressure.

30. Changes in Afterload and Preload n  fluid volume…  n  preload… n  contractility (Starling’s Law)… n  cardiac output. n  blood pressure.

31. FluidFluid nMust have adequate amounts of hemoglobin nMust have adequate intravascular volume nMust have adequate amounts of hemoglobin nMust have adequate intravascular volume

32. Maintenance of Fluid Volume nRenin-Angiotensin-Aldosterone system.  Works through kidneys to regulate balance of Na + and water. nRenin-Angiotensin-Aldosterone system.  Works through kidneys to regulate balance of Na + and water.

33. Renin-Angiotensin-AldosteroneRenin-Angiotensin-Aldosterone  Plasma volume volume  [Na+] Kidney(juxtaglomerularapparatus)Kidney(juxtaglomerularapparatus) Detected by Releases ReninRenin Angiotensinogen Angiotensin I… Converts &/Or Via ACE (Angiotensin Converting Enzyme) Angiotensin II…

34. Renin-Angiotensin-AldosteroneRenin-Angiotensin-Aldosterone  vasoconstriction  PVR  BP!  thirst  Fluid volume volume  ADH (anti-diuretichormone) (anti-diuretichormone) AdrenalcortexAdrenalcortex Releases AldosteroneAldosterone  Na+ reabsorption reabsorption

35. HemostasisHemostasis nThe stoppage of bleeding. nThree methods  Vascular constriction  Platelet plug formation  Coagulation nThe stoppage of bleeding. nThree methods  Vascular constriction  Platelet plug formation  Coagulation

36. CoagulationCoagulation nFormation of blood clots nProthrombin activator nProthrombin  thrombin nFibrinogen  fibrin nClot retraction nFormation of blood clots nProthrombin activator nProthrombin  thrombin nFibrinogen  fibrin nClot retraction

37. FibrinolysisFibrinolysis nPlasminogen nTissue plasminogen activator (tPA) nPlasmin nPlasminogen nTissue plasminogen activator (tPA) nPlasmin

38. Disseminated Intravascular Coagulation “A systemic thrombohemorrhagic disorder … with evidence of: 1)Procoagulant activation 2)Fibrinolytic activation 3)Inhibitor consumption 4)End-organ failure” “A systemic thrombohemorrhagic disorder … with evidence of: 1)Procoagulant activation 2)Fibrinolytic activation 3)Inhibitor consumption 4)End-organ failure” Bick, R.L. Seminars in Thrombosis and Hemostasis 1996

39. Pathophysiology of DIC nUncontrolled acceleration of clotting cascade nSmall vessel occlusion nOrgan necrosis nDepletion of clotting factors nActivation of fibrinolysis nUltimately severe systematic hemorrhage nUncontrolled acceleration of clotting cascade nSmall vessel occlusion nOrgan necrosis nDepletion of clotting factors nActivation of fibrinolysis nUltimately severe systematic hemorrhage

40. ContainerContainer nVasculature is continuous, closed and pressurized system nMicrocirculation responds to local tissue needs nBlood flow dependent on PVR nVasculature is continuous, closed and pressurized system nMicrocirculation responds to local tissue needs nBlood flow dependent on PVR

41. Fick Principle nEffective movement and utilization of O 2 dependent on:  Adequate fio 2  Appropriate O 2 diffusion into bloodstream  Adequate number of RBCs  Proper tissue perfusion  Efficient hemoglobin ‘loading’ nEffective movement and utilization of O 2 dependent on:  Adequate fio 2  Appropriate O 2 diffusion into bloodstream  Adequate number of RBCs  Proper tissue perfusion  Efficient hemoglobin ‘loading’

42. Fick Principle nPerfusion = Arterial O 2 Content - Venous O 2 Content nAffected by:  Hemoglobin levels  circulation of RBCs  distance between alveoli and capillaries  pH and temperature nPerfusion = Arterial O 2 Content - Venous O 2 Content nAffected by:  Hemoglobin levels  circulation of RBCs  distance between alveoli and capillaries  pH and temperature

43. Onloading Oxygen in Lungs Pressure Saturation oxyhemeglobin deoxyhemeglobin pH 7.4 pH 7.45  pH shifts curve to left  pH shifts curve to left  ‘onloading’ in lungs  ‘onloading’ in lungs  pH shifts curve to left  pH shifts curve to left  ‘onloading’ in lungs  ‘onloading’ in lungs Remember: CO 2  [H + ] Remember:

44. Offloading Oxygen in Tissues Pressure Saturation oxyhemeglobin deoxyhemeglobin pH 7.4 pH 7.35  pH shifts curve to right  pH shifts curve to right  ‘offloading’ to tissues  ‘offloading’ to tissues  pH shifts curve to right  pH shifts curve to right  ‘offloading’ to tissues  ‘offloading’ to tissues Remember: CO 2  [H + ] Remember:

45. Causes of Inadequate Perfusion nInadequate pump  Inadequate preload  Poor contractility  Excessive afterload  Inadequate heart rate nInadequate fluid volume  Hypovolemia nInadequate container  Excessive dilation  Inadequate systematic vascular resistance nInadequate pump  Inadequate preload  Poor contractility  Excessive afterload  Inadequate heart rate nInadequate fluid volume  Hypovolemia nInadequate container  Excessive dilation  Inadequate systematic vascular resistance

46. Responses to Shock nNormal compensation includes:  Progressive vasoconstriction  Increased blood flow to major organs  Increased cardiac output  Increased respiratory rate and volume  Decreased urine output nNormal compensation includes:  Progressive vasoconstriction  Increased blood flow to major organs  Increased cardiac output  Increased respiratory rate and volume  Decreased urine output

47. Cellular Response to Shock  Tissue perfusion perfusion  Na + Pump Function Function  ATP synthesis synthesis AnaerobicmetabolismAnaerobicmetabolism  Cellular edema  Vascular volume  Cellular edema  Vascular volume Impaired cellular metabolism metabolism  O 2 use use Intracellular Na +  Intracellular Na + & water Intracellular Na +  Intracellular Na + & water ImpairedglucoseusageImpairedglucoseusage Stimulation of clotting cascade & inflammatoryresponse Stimulation of clotting cascade & inflammatoryresponse

48. Stages of Shock nCompensated nUncompensated nIrreversible nCompensated nUncompensated nIrreversible

49. Compensated Shock nDefense mechanisms are successful in maintaining perfusion nPresentation  Tachycardia  Decreased skin perfusion  Altered mental status nDefense mechanisms are successful in maintaining perfusion nPresentation  Tachycardia  Decreased skin perfusion  Altered mental status

50. Uncompenstated Shock nDefense mechanisms begin to fail nPresentation  Hypotension  Prolonged Cap refill  Marked increase in heart rate  Rapid, thready pulse  Agitation, restlessness, confusion nDefense mechanisms begin to fail nPresentation  Hypotension  Prolonged Cap refill  Marked increase in heart rate  Rapid, thready pulse  Agitation, restlessness, confusion

51. Irreversible Shock nComplete failure of compensatory mechanisms nDeath even in presence of resuscitation nComplete failure of compensatory mechanisms nDeath even in presence of resuscitation

52. Types of Shock nHypovolemic nCardiogenic nNeurogenic nAnaphylactic nSeptic nHypovolemic nCardiogenic nNeurogenic nAnaphylactic nSeptic

53. Hypovolemic Shock n“Fluid failure” nDecreased intravascular volume nCauses? n“Third spacing” n“Fluid failure” nDecreased intravascular volume nCauses? n“Third spacing”

54. Cardiogenic Shock  CO R.A.S.ActivationR.A.S.Activation  Dyspnea  O 2 supply supply  Volume/ Preload Preload  SVR  Peripheral & pulmonary edema  Peripheral & pulmonary edema Impaired myocardial function Impaired  Myocardial O 2 demand  Myocardial O 2 demand  Catecholamine Release Release

55. Neurogenic Shock  Sympathetic Tone Or  Parasympathetic Tone  Sympathetic Tone Or  Parasympathetic Tone  Vascular Tone Massive Vasodilation  SVR & Preload  Cardiac Output  Tissue perfusion perfusion

56. Anaphylactic Shock n“Container failure” nMassive & systemic allergic reaction nLarge release of histamine nIncreases membrane permeability & vasodilation n“Container failure” nMassive & systemic allergic reaction nLarge release of histamine nIncreases membrane permeability & vasodilation

57. Septic Shock n“Container failure” nSystemic infection n“Container failure” nSystemic infection

58. Multiple Organ Dysfunction System nProgressive dysfunction of two or more organ systems nCaused by uncontrolled inflammatory response to injury or illness  Typically sepsis nProgressive dysfunction of two or more organ systems nCaused by uncontrolled inflammatory response to injury or illness  Typically sepsis

59. ReferencesReferences nNew York Presbyterian hospital hypertension center: nNew York Presbyterian hospital hypertension center:  Http://pc101186.Med.Cornell.edu/htchome/htbk/Htbkindex.ht m Http://pc101186.Med.Cornell.edu/htchome/htbk/Htbkindex.ht m Http://pc101186.Med.Cornell.edu/htchome/htbk/Htbkindex.ht m nBiographics Gallery: http://www.accessexcellence.com/AB/GG/#Anchor- Building-11481 http://www.accessexcellence.com/AB/GG/#Anchor- Building-11481 http://www.accessexcellence.com/AB/GG/#Anchor- Building-11481 nRAS (Renin-Angiotensin-Aldosterone System):  http://www.science.mcmaster.ca/Biology/4S03/RAS.HTM http://www.science.mcmaster.ca/Biology/4S03/RAS.HTM nA graduate student’s hypertension page:  http://www.teaching- biomed.man.ac.uk/student_projects/2000/mnpm6ven/default.h tm http://www.teaching- biomed.man.ac.uk/student_projects/2000/mnpm6ven/default.h tm http://www.teaching- biomed.man.ac.uk/student_projects/2000/mnpm6ven/default.h tm nNew York Presbyterian hospital hypertension center: nNew York Presbyterian hospital hypertension center:  Http://pc101186.Med.Cornell.edu/htchome/htbk/Htbkindex.ht m Http://pc101186.Med.Cornell.edu/htchome/htbk/Htbkindex.ht m Http://pc101186.Med.Cornell.edu/htchome/htbk/Htbkindex.ht m nBiographics Gallery: http://www.accessexcellence.com/AB/GG/#Anchor- Building-11481 http://www.accessexcellence.com/AB/GG/#Anchor- Building-11481 http://www.accessexcellence.com/AB/GG/#Anchor- Building-11481 nRAS (Renin-Angiotensin-Aldosterone System):  http://www.science.mcmaster.ca/Biology/4S03/RAS.HTM http://www.science.mcmaster.ca/Biology/4S03/RAS.HTM nA graduate student’s hypertension page:  http://www.teaching- biomed.man.ac.uk/student_projects/2000/mnpm6ven/default.h tm http://www.teaching- biomed.man.ac.uk/student_projects/2000/mnpm6ven/default.h tm http://www.teaching- biomed.man.ac.uk/student_projects/2000/mnpm6ven/default.h tm