1. Awatif Jamal, MD, MSc, FRCPC, FIAC Consultant & Associate Professor Department of Pathology King Abdulaziz University Hospital

2. Hemodynamic Disorders Thrombosis & Shock Shock Shock

3. Shock or cardiovascular collapse Shock constitutes systemic hypo perfusion due to Shock constitutes systemic hypo perfusion due to reduction either in : reduction either in : --cardiac output --cardiac output --or in the effective circulating blood volume. --or in the effective circulating blood volume. It is the common final pathway for a number of It is the common final pathway for a number of potentially lethal events including ; potentially lethal events including ; severe hemorrhage severe hemorrhage Extensive trauma Extensive trauma Severe burns Severe burns Large myocardial infarction Large myocardial infarction Massive pulmonary embolism Massive pulmonary embolism Massive microbial sepsis. Massive microbial sepsis.

4. Shock or cardiovascular collapse The end results are: 1.Hypotension, followed by 1.Hypotension, followed by 2.Impaired Tissue Perfusion 2.Impaired Tissue Perfusion 3.Cellular Hypoxia 3.Cellular Hypoxia 4. Hypoxic and metabolic effects of hypoperfusion causes initially reversible cell injury. 4. Hypoxic and metabolic effects of hypoperfusion causes initially reversible cell injury. 5. Persistence of shock causes irreversible cell injury, even to death of patient. 5. Persistence of shock causes irreversible cell injury, even to death of patient.

5. Shock Shock or “cardiovascular collapse” could be grouped into three Main Categories: Shock or “cardiovascular collapse” could be grouped into three Main Categories: Cardiogenic shock Cardiogenic shock Hypovolemic shock Hypovolemic shock Septic shock Septic shock Others: Others: Neurogenic Shock (spinal cord injury) Neurogenic Shock (spinal cord injury) Anaphylactic Shock Anaphylactic Shock

6. Cardiogenic Shock Results From Severe Myocardial Pump Failure Due to: Results From Severe Myocardial Pump Failure Due to: Myocardial Infarction Myocardial Infarction Ventricular Arrhythmia Ventricular Arrhythmia Extrinsic Compression (Cardiac Tamponade) Extrinsic Compression (Cardiac Tamponade) Outflow Obstruction (Pulmonary Embolism) Outflow Obstruction (Pulmonary Embolism)

7. Hypovolemic Shock Results From Loss of Blood or Plasma Volume: Results From Loss of Blood or Plasma Volume: Hemorrhage Hemorrhage Fluid loss from severe burns or trauma Fluid loss from severe burns or trauma

8. NEUROGENIC SHOCK In case of spinal cord injury or anesthetic accident which can lead to; In case of spinal cord injury or anesthetic accident which can lead to; Loss of vascular tone Loss of vascular tone And peripheral pooling of blood And peripheral pooling of blood

9. ANAPHYLACTIC SHOCK Initiated by generalized Ig E-mediated hypersensitivity reaction associated with systemic vasodilatation and increased vascular permeability. Initiated by generalized Ig E-mediated hypersensitivity reaction associated with systemic vasodilatation and increased vascular permeability.

10. Septic Shock Most common cause of death in ICU’s in the US The incidence is increasing due to; The incidence is increasing due to;  Improved life support for high-risk patients  Increased invasive procedures  Increasing number of immunocompromized cases as HIV infection, secondary to chemotherapy, and immunosuppression.  Caused by systemic microbial infection; most often by endotoxins-producing gram-negative bacilli infection (endotoxic shock) [in 70% of cases], but can also occur with gram-positive and fungal infections

11. Pathogenesis Of Endotoxic [Septic] Shock Endotoxins are bacterial wall lipopolysaccharides (LPS) which consists of ; --a toxic fatty acid (lipid A) core and --a toxic fatty acid (lipid A) core and --a complex polysaccharide coat. --a complex polysaccharide coat. LPS are released when the cell walls are degraded in an inflammatory response.

12. Pathogenesis Of Endotoxic [Septic] Shock Free LPS attaches to circulating LPS- binding proteins, Free LPS attaches to circulating LPS- binding proteins, It will then bind to a receptor ( CD14) in macrophages, monocytes, and neutrophils leading to their activation and production of TNF, and IL-1. It will then bind to a receptor ( CD14) in macrophages, monocytes, and neutrophils leading to their activation and production of TNF, and IL-1. Depending on the dose and number of macrophages that are activated,the secondary effects of LPS release can cause severe pathologic changes including the fatal shock. Depending on the dose and number of macrophages that are activated,the secondary effects of LPS release can cause severe pathologic changes including the fatal shock.

13. Pathogenesis Of Septic Shock High quantities of LPS  High quantities of LPS  systemic vasodilatation (hypotension) systemic vasodilatation (hypotension) diminished cardiac contractility (low cardiac output) diminished cardiac contractility (low cardiac output) endothelial injury and activation  leukocyte adhesion endothelial injury and activation  leukocyte adhesion activation of coagulation system ( Disseminated Intravascular Coagulopathy) activation of coagulation system ( Disseminated Intravascular Coagulopathy) adult respiratory distress syndrome ( ARDS) adult respiratory distress syndrome ( ARDS) multiorgan system failure and death multiorgan system failure and death

14. Stages of Shock: Shock is a progressive disorder that evolves through 3 stages, and if uncorrected will lead to death. Initial “Non-progressive stage”: Initial “Non-progressive stage”: Reflex compensatory mechanism activation  maintain perfusion of vital organs through maintenance of cardiac output and blood pressure. Reflex compensatory mechanism activation  maintain perfusion of vital organs through maintenance of cardiac output and blood pressure. C/P; tachycardia, C/P; tachycardia, peripheral vasoconstriction,cold skin, pallor (although septic shock may be associated with inflammation and hotness) peripheral vasoconstriction,cold skin, pallor (although septic shock may be associated with inflammation and hotness) Shock

15. Stages of Shock Irreversible stage: Irreversible stage: Severe cellular and tissue injury  thus survival is not possible Severe cellular and tissue injury  thus survival is not possible Acute renal tubular necrosis Acute renal tubular necrosis Adult respiratory distress syndrome ( ARDS ) Adult respiratory distress syndrome ( ARDS ) Bowel ischemia and release of its flora. Bowel ischemia and release of its flora. Disseminated Intravascular Coagulopathy Disseminated Intravascular Coagulopathy “Progressive stage: “Progressive stage: tissue hypo perfusion with widespread hypoxia  circulatory & metabolic imbalance. tissue hypo perfusion with widespread hypoxia  circulatory & metabolic imbalance. C/P: patient is confused C/P: patient is confused Reduced urine output. Reduced urine output.

16. Disseminated Intravascular Coagulation (DIC) Sudden widespread fibrin deposition in microcirculation Sudden widespread fibrin deposition in microcirculation Rapid consumption of platelets and coagulation proteins (consumption coagulopathy) Rapid consumption of platelets and coagulation proteins (consumption coagulopathy) Secondary massive fibrinolysis, all the little thrombi dissolve Secondary massive fibrinolysis, all the little thrombi dissolve Clotting disorder turns into a Bleeding Disaster Clotting disorder turns into a Bleeding Disaster