1 SHOCK , PATHOPHYSIOLOGY Prof.M.H.MUMTAZ.Energy Metabolism Perfusion Shock

2 Topics Define shock in terms of cellular functionReview the requirements for adequate cellular perfusion (Fick principle) Review the mechanisms for starling’s law Preload vs. afterload Muscle contraction

3 Topics Continued Discuss the mechanisms for oxygen transportoxyhemoglobin dissociation curve Define the stages of shock Describe different causes of shock Define multiple organ dysfunction syndrome

4 Shock Defined Inadequate tissue perfusion Anaerobic metabolismFinal Common Pathway!

5 Aerobic Metabolism 6 CO2 6 O2 6 H2O METABOLISM 36 ATP GLUCOSEHEAT (417 kcal)

6 Anaerobic Metabolism 2 LACTIC ACID GLUCOSE METABOLISM 2 ATPHEAT (32 kcal)

7 Anaerobic? So What? Inadequate Cellular Oxygenation AnaerobicMetabolism Inadequate Energy Production Lactic Acid Production Metabolic Failure Metabolic Acidosis Cell Death!

8 Homeostasis is maintenance of balanceRequires proper functioning systems Cardiovascular Respiratory Renal

9 Physiology of PerfusionDependant on 3 components of circulatory system Pump Fluid Container

10 Factors Affecting The PumpPreload Contractile force Frank-starling mechanism Afterload

11 Muscle Anatomy

12 Contraction: Sliding Filamentsimage from:

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

14 What Affects Blood Pressure?ANS balance Contractility Preload Starling’s law Afterload

15 Autonomic Nervous System Review…Quiz Time! Yeah!

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

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

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

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

20 Jeopardy Two types classes of sympathetic receptors. What isalpha and beta?

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

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

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

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

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

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

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

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

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

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

31 Fluid Must have adequate amounts of hemoglobinMust have adequate intravascular volume

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

33 Renin-Angiotensin-AldosteronePlasma volume Kidney (juxtaglomerular apparatus) Detected by &/Or  [Na+] Releases Renin Via ACE (Angiotensin Converting Enzyme) Angiotensin II… Angiotensinogen Angiotensin I… Converts

34 Renin-Angiotensin-Aldosterone vasoconstriction  PVR Angiotensin II…  BP!  thirst Adrenal cortex Releases Aldosterone ADH (anti-diuretic hormone) Fluid volume Na+ reabsorption

35 Hemostasis The stoppage of bleeding. Three methodsVascular constriction Platelet plug formation Coagulation

36 Coagulation Formation of blood clots Prothrombin activatorProthrombin  thrombin Fibrinogen  fibrin Clot retraction

37 Fibrinolysis Plasminogen Tissue plasminogen activator (tPA) Plasmin

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

39 Pathophysiology of DICUncontrolled acceleration of clotting cascade Small vessel occlusion Organ necrosis Depletion of clotting factors Activation of fibrinolysis Ultimately severe systematic hemorrhage

40 Container Vasculature is continuous, closed and pressurized systemMicrocirculation responds to local tissue needs Blood flow dependent on PVR

41 Fick Principle Effective movement and utilization of O2 dependent on:Adequate fio2 Appropriate O2 diffusion into bloodstream Adequate number of RBCs Proper tissue perfusion Efficient hemoglobin ‘loading’

42 Fick Principle Perfusion = Arterial O2 Content - Venous O2 ContentAffected by: Hemoglobin levels circulation of RBCs distance between alveoli and capillaries pH and temperature

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46 Onloading Oxygen in Lungsoxyhemeglobin pH 7.45 Remember: CO2  [H+] pH 7.4 Saturation  pH shifts curve to left  ‘onloading’ in lungs deoxyhemeglobin Pressure

47 Offloading Oxygen in Tissuesoxyhemeglobin pH 7.4 Remember: CO2  [H+] pH 7.35 Saturation pH shifts curve to right  ‘offloading’ to tissues deoxyhemeglobin Pressure

48 Causes of Inadequate PerfusionInadequate pump Inadequate preload Poor contractility Excessive afterload Inadequate heart rate Inadequate fluid volume Hypovolemia Inadequate container Excessive dilation Inadequate systematic vascular resistance

49 Responses to Shock Normal compensation includes:Progressive vasoconstriction Increased blood flow to major organs Increased cardiac output Increased respiratory rate and volume Decreased urine output

50 Cellular Response to Shockuse Tissue perfusion Impaired cellular metabolism Anaerobic metabolism Stimulation of clotting cascade & inflammatory response Impaired glucose usage ATP synthesis  Intracellular Na+ & water Na+ Pump Function Cellular edema  Vascular volume

51 Stages of Shock Compensated Uncompensated Irreversible

52 Compensated Shock Defense mechanisms are successful in maintaining perfusion Presentation Tachycardia Decreased skin perfusion Altered mental status

53 Uncompenstated Shock Defense mechanisms begin to fail PresentationHypotension Prolonged Cap refill Marked increase in heart rate Rapid, thready pulse Agitation, restlessness, confusion

54 Irreversible Shock Complete failure of compensatory mechanismsDeath even in presence of resuscitation

55 Types of Shock Hypovolemic Cardiogenic Neurogenic Anaphylactic Septic

56 Hypovolemic Shock “Fluid failure” Decreased intravascular volumeCauses? “Third spacing”

57 Cardiogenic Shock Catecholamine R.A.S.  CO Release Activation  SVRImpaired myocardial function  SVR Volume/ Preload Myocardial O2 demand O2 supply Peripheral & pulmonary edema  Dyspnea

58  Parasympathetic ToneNeurogenic Shock  Sympathetic Tone Or  Parasympathetic Tone Vascular Tone Massive Vasodilation Tissue perfusion  SVR & Preload  Cardiac Output

59 Anaphylactic Shock “Container failure”Massive & systemic allergic reaction Large release of histamine Increases membrane permeability & vasodilation

60 Septic Shock “Container failure” Systemic infection

61 Multiple Organ Dysfunction SystemProgressive dysfunction of two or more organ systems Caused by uncontrolled inflammatory response to injury or illness Typically sepsis

62 References New York Presbyterian hospital hypertension center: Biographics Gallery: RAS (Renin-Angiotensin-Aldosterone System): A graduate student’s hypertension page: