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

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

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

Shock Defined Inadequate tissue perfusion Anaerobic metabolism Final Common Pathway!

Aerobic Metabolism 6 CO2 6 O2 6 H2O METABOLISM 36 ATP GLUCOSE HEAT (417 kcal)

Anaerobic Metabolism 2 LACTIC ACID GLUCOSE METABOLISM 2 ATP HEAT (32 kcal)

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

Homeostasis is maintenance of balance Requires proper functioning systems Cardiovascular Respiratory Renal

Physiology of Perfusion Dependant on 3 components of circulatory system Pump Fluid Container

Factors Affecting The Pump Preload Contractile force Frank-starling mechanism Afterload

Muscle Anatomy

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

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

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

Autonomic Nervous System Review… Quiz Time! Yeah!

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?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Fluid Must have adequate amounts of hemoglobin Must have adequate intravascular volume

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

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

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

Hemostasis The stoppage of bleeding. Three methods Vascular constriction Platelet plug formation Coagulation

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

Fibrinolysis Plasminogen Tissue plasminogen activator (tPA) Plasmin

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

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

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

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’

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

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

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

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

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

Cellular Response to Shock use 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

Stages of Shock Compensated Uncompensated Irreversible

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

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

Irreversible Shock Complete failure of compensatory mechanisms Death even in presence of resuscitation

Types of Shock Hypovolemic Cardiogenic Neurogenic Anaphylactic Septic

Hypovolemic Shock “Fluid failure” Decreased intravascular volume Causes? “Third spacing”

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

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

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

Septic Shock “Container failure” Systemic infection

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

References New York Presbyterian hospital hypertension center: Http://pc101186.Med.Cornell.edu/htchome/htbk/Htbkindex.htm Biographics Gallery: http://www.accessexcellence.com/AB/GG/#Anchor-Building-11481 RAS (Renin-Angiotensin-Aldosterone System): http://www.science.mcmaster.ca/Biology/4S03/RAS.HTM A graduate student’s hypertension page: http://www.teaching-biomed.man.ac.uk/student_projects/2000/mnpm6ven/default.htm