General Principles of Pathophysiology

General Principles of Pathophysiology : 

General Principles of Pathophysiology Energy Metabolism Perfusion Shock

Topics : 

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 : 

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 : 

Shock Defined Inadequate tissue perfusion Anaerobic metabolism Final Common Pathway!

Aerobic Metabolism : 

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

Anaerobic Metabolism : 

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

Anaerobic? So What? : 

Anaerobic? So What? Inadequate Cellular Oxygenation

Homeostasis is maintenance of balance : 

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

Physiology of Perfusion : 

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

Factors Affecting The Pump : 

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

Muscle Anatomy : 

Muscle Anatomy

Contraction: Sliding Filaments : 

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

What Is Blood Pressure? : 

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

What Affects Blood Pressure? : 

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

Autonomic Nervous System Review… : 

Autonomic Nervous System Review… Quiz Time! Yeah!

Jeopardy : 

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

Jeopardy : 

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

Jeopardy : 

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

Jeopardy : 

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

Jeopardy : 

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

Jeopardy : 

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

Jeopardy : 

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

Jeopardy : 

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

Jeopardy : 

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

Jeopardy : 

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

Jeopardy : 

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

Changes in Afterload and Preload : 

Changes in Afterload and Preload  Peripheral vasoconstriction… 

Changes in Afterload and Preload : 

Changes in Afterload and Preload  Peripheral vasodilation…  

Changes in Afterload and Preload : 

Changes in Afterload and Preload  fluid volume… 

Changes in Afterload and Preload : 

Changes in Afterload and Preload  fluid volume… 

Fluid : 

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

Maintenance of Fluid Volume : 

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

Renin-Angiotensin-Aldosterone : 

Renin-Angiotensin-Aldosterone Plasma volume  [Na+] &/Or

Renin-Angiotensin-Aldosterone : 

Renin-Angiotensin-Aldosterone Angiotensin II…

Hemostasis : 

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

Coagulation : 

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

Fibrinolysis : 

Fibrinolysis Plasminogen Tissue plasminogen activator (tPA) Plasmin

Disseminated Intravascular Coagulation : 

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 : 

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 : 

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

Fick Principle : 

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 : 

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 : 

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

Offloading Oxygen in Tissues : 

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

Causes of Inadequate Perfusion : 

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 : 

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 : 

Cellular Response to Shock Tissue perfusion

Stages of Shock : 

Stages of Shock Compensated Uncompensated Irreversible

Compensated Shock : 

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

Uncompenstated Shock : 

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 : 

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

Types of Shock : 

Types of Shock Hypovolemic Cardiogenic Neurogenic Anaphylactic Septic

Hypovolemic Shock : 

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

Cardiogenic Shock : 

Cardiogenic Shock  CO

Neurogenic Shock : 

Neurogenic Shock  Sympathetic Tone Or  Parasympathetic Tone

Anaphylactic Shock : 

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

Septic Shock : 

Septic Shock “Container failure” Systemic infection

Multiple Organ Dysfunction System : 

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

References : 

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