Pathophysiology of shock

anesthesia & pathophysiology of shock

1. PATHOPHYSIOLOGY OF SHOCK MODERATOR: Dr. TARUN SINGH PRESENTER: Dr. RICHA KUMAR

2. DEFINITION Shock is failure of cardiovascular system to provide oxygen transport necessary to meet oxygen demand It is final common pathway resulting in systemic hypoperfusion  hypotension impaired tissue perfusion cellular hypoxia-  anaerobic metabolism Underlying pathology can be :- Severe haemorrhage , extensive trauma or burns, MI, massive pulmonary embolism and microbiological sepsis Hypoxic and metabolic effects initially cause reversible cellular injury Persistence of shock causes irreversible tissue injury and culminate on death of patient

3. Can result from four basic mechanism: Reduced intravascular volume Failure of cardiac pump Obstruction of circulation Distributive disorders of peripheral circulation First three mechanism result in low cardiac output  tissue hypoperfusion & microcirculatory abnormalities Every type of shock can eventually lead to distributive shock due to inflammatory response elicited by persistent tissue hypoxia

4. PHYSIOLOGY OF MICROCIRCULATION Microcirculation= tissue oxygenation Determined by 2 mechanisms: Convection Diffusion Depends on determined by: Microcirc . Oxygen content 1. gradient between Blood flow capillary and mitochondrial PO2 2. diffusional distance Controlled by arteriolar 3. area available for gas Resistance vessels tone exchange increase in Arteriolar resistance also decreases hematocrit.

5. THREE MAJOR TYPES OF SHOCK TYPE CLINICAL EXAMPLES PRINCIPAL MECHANISM Cardiogenic MI Ventricular rupture Arrythmias Cardiac tamponade Pulmonary embolism Failure of myocardial pump owing to intrinsic myocardial damage, extrinsic pressure or obstruction to flow Hypovolemia Hemorrhage Fluid loss Inadequate blood & plasma level Septic Overwhelming microbial infection Gram - septicemia Endotoxic shock Fungal sepsis superantigens Peripheral vasodilation & pooling of blood Endothelial activation Leukocyte induced damage DIC Activation of cytokine cascades

6. Less common types: Neurogenic shock : Anaesthetic accident or spinal cord injury it is due to loss of vascular tone and peripheral pooling of blood Anaphylactic shock : IgE mediated hypersensitivity response  widespread vasodilatation, increased vascular permeability  sudden increase in vascular bed capacitance which is not filled up by the normal blood volume hypoperfusion  cellular anoxia

7. PATHOGENESIS OF SEPTIC SHOCK Most cases due to gram negative bacilli (endotoxin producing) Endotoxin are bacterial cell wall LPS, released when cell wall is degraded Endotoxin consist of toxic fatty acid (lipid A) core and complex polysaccharide core  unique to each species

8. LPS + LPS binding protein This complex binds to cell surface receptor CD14, TLR -4 & Stimulate immune response Directly activate vascular wall cells /leukocytes/initiate cascade of cytokine mediators On endothelial cells  Downregulation of natural anticoagulation mechanism (decrease tissue factor pathway inhibitor & thrombodulin ) On monocytes and macrophages mononuclear cell activation production of potent cytokines like IL1, TNF This mechanism normally helps to isolate organisms and eradicate invading microbes Depending on dosage and numbers of macrophages that are activated , the seccondary effects of LPS release can lead to severe pathologic changes, including fatal shock

9. At low doses initial release of LPS results in circumscribed cytokines casscade intended to enhance local acute inflammatory response and improve clearance of the infection Moderately severe infections  cytokine mediated secondary effectors like NO become significant + systemic effects if TNF IL1 start appearing like fever and increased synthesis of acute phase reactants At higher dosage the same cytokines and interleukines now at higher dosage result in Systemic vasodilatation (hypotension) Diminished myocardial contractility Widespread endothelial injury & activation causing systemic leukocyte adhesion and pulmonary capillary damage (ARDS) Activation of coagulation system, culminating in DIC

10. Widespread vasodilation, myocardial pump failure, DIC  hypoperfusion  MULTI ORGAN FAILURE affecting liver, kidneys, CNS Unless the underlying infection and LPS overload are brought under control the patient usually dies. An interesting groups of bacterial proteins called SUPERANTIGENS cause syndrome similar to septic shock

11. PATHOPHYSIOLOGY OF HAEMORRHAGIC SHOCK Characterized by both  macrovascular hemodynamic abnormalities decreased venous return , decreased cardiac output and systemic hypotension Alterations in microcirculation In acute phase of haemorrhage , macrovascular and microvascular responses rapidly act to compensate for loss of blood volume and to limit tissue hypoxia

12. MACROVASCULAR RESPONSE Involves autonomic nervous system Decrease in venous return and arterial pressure leads to Unloading of cardiopulmonary and arterial baroreceptors Decrease in vasomotor inhibitory centres in brainstem Activation of sympathetic centre , inhibition of vagal centre (SAN) Increase HR, cardiac contractility & arterial and venous tone , RAS+ Magnitude of compensatory VC depends on net result of interaction betwenn NE (from periphery) & epinephrine (adrenal medulla) VC  decreases non vital organ blood flow to maintain perfusion presuure to vital organs Venous VC  maintains venous return and cardiac output

13. MICROVASCULAR RESPONSE Responds to changes in metabolic demands by limiting blood flow in microcircular units with low oxygen demand and increasing blood flow in those units with high oxygen demand This microvascular heterogenesity is essential component of normal microvascular perfusion to provide adequate DO2 for the tissue The microvascular units with severely reduced blood flow might adjust their function and their energy utilization to prevent hypoxia Two mechanism are proposed to account for local oxygen delivery  regulation of arteriolar tone  control of functional surface area for oxygen demand

14. REGUALTION OF ARETRIOLAR TONE Decreased pO2  arterioles dilate- increase perfusion & DO2 Arteriolar tone is net result of: ANS, vasoactive substances in blood, local regulators of arteriolar tone Local regulation is a crucial factor in microcirculation regulation to match oxygen supply to oxygen demand Several mechanisms of local regulation : intraluminal pressure ( myogenic response ) shear stress on endothelial cells ( shear dependent response ) tissue metabolite concentration ( metabolic response)

15. MYOGENIC RESPONSE : Refers to intrinsic ability of blood vessels to constrict and increase intraluminal pressure or dilate and decrease intraluminal pressure SHEAR DEPENDENT RESPONSE : it is vasodilatation induced by shear stress ( NO-dependent mechanism) Dependent on endothelial sensing/transduction of the shear induced by blood flow Mechanoreceptors on luminal surface of endothelium : glycocalyx (glycoproteins / proteoglycans) Stretch activated ion channels Cytoskeletal arrangements Cell-cell & cell- ECM connections

16. METABOLIC RESPONSE : allows vascular tone to adapt to cellular oxygen demand Hmgic shock  decreased in DO2 decreased ATP ADP accumulates increased ADP degradation products ( AMP,adenosine ) glycolysis is activated increased lactate & H+ ions adenosine , lactate and H+  arteiolar vasodilators Reduced CO2 clearance  accumulates powerful vasodilator

17. An increasingly important role in microvascular tone regulation & matching oxygen supply to demand is being attributed to the RBC and hemoglobin molecule RBC behaves as mobile oxygen sensor and controls vascular tone by means of release of ATP Low PO2,  decreased oxygen saturated hemoglobin  mechanical deformation of membrane ATP is released from RBC This ATP interacts with endothelial purinergic receptors (including VD mediators) VD is conducted  increased blood supply to area with increased oxygen demand

18. CONTROL OF FUNCTIONAL SURFACE ARE OF OXYGEN EXCHANGE Oxygen extraction depends on Incoming b lood flow = convective oxygen transport  mainly determined by arteriolar tone Functional area of oxygen exchange= diffusive oxygen transport related to number of RBCs  number of capillaries increase in capillaries facilitates oxygen transport by: a) increase in surface area for oxygen exchange b) decrease capillary to mitochondrial diffusion distances

19. Diagram

20. The high capillary density can be achieved by recruiting capillaries that is initiation of RBC influx in previously non-flowing capillaries In some microvascular beds like skeletal or myocardium, most capillaries sustain RBC flux at rest and capillary recruitment does not occur  oxygen extraction is dependent on the distribution of RBCs within previously flowing capillaries Capillary resistance and rheological factors ( blood viscosity and RBC deformability) determine RBC distribution within capillary bed crucial role in determining capillary homogeneity and functional capillary density esp at low flow rates

21. Acute phase haemorrhagic shock Decrease in capillary pressure Net fluid absorption from interstitium to vascular compartment Restore blood volume This effect + hemodilution during resuscitation phase Decreases blood viscosity Decrease hetergenesity of RBC distribution Late phase  inflammatory cells  fluid leakage with fluid shift to interstial compartment increase viscosity and heterogenesity of RBC distribution

22. ALTERATIONS IN MICROCIRCULATION IN HEMORRHAGIC SHOCK Despite efficient microvascular adaptive mechanisms When blood loss severe Progressive decrease in cardiac output & oxygen delivery Progressive decrease in capillary blood flow , RBC velocities , functional capillary density Increase flow heterogeneity Increase in RBC aggregation Blood flow slow + intermittent or no flow capillaries + “plasmatic capillaries” Contribute to increase heterogeneity

23. Increase heterogeneity + hemorrhagic shock induced RBC damage Decrease microvascular PO2 through: 1. Direct diffusion of oxygen from arterioles to venules in close approximity (convective A-V shunting) 2. Functional shunting of disadvantageous microvascular units Early resuscutation may improve time course of microcirculatory dysfunction and eventually patient outcome. But later when inflammatory response is marked, sepsis like microvascular alterations may be observed despite macrovascular resuscutation and is associated with organ failure

24. diagram

25. PATHOGENESIS OF CARDIOGENIC SHOCK

26. STAGES OF SHOCK INITIAL NON PROGRESSIVE PHASE: reflex compensatory mechanisms are activated and perfusion of vital organs is maintained PROGRESSIVE STAGE: characterised bytissue hypoperfusion and onset of worsening circulatory and metabolic imbalances,and acidosis IRREVERSIBLE STAGE: sets in after body has incurred cellular and tissue injuty so severe that even if hemodynamic defects are corrected survival is not possible

27. NON-PROGRESSIVE PHASE: Variety of neurohumoral mechanisms help maintain cardiac output and blood pressure 1. baroreceptor reflexes— 2. release of caecholamines 3. activation of RAAS 4. ADH release 5. generalized symoathetic stimulation Net effect is tachycardia, peripheral VC, renal conservationof fluid Eg . Cutaneous VC  pallor of skin Cerebral and coronary vessels are less sensitive to these compensatory sympathetic changes maintain normal caliber, blood flow, oxygen delivery

28. PROGRESSIVE PHASE: if underlying causes are not corrected in reversible phase There is widespread tissue hypoxia Intracellular aerobic respiration is replaced by anaerobic glycolysis Excessive production of lactic acid Lowering of tissue pH , blunting of vasomotor response Arteriole dilate, blood begins to pool in microcirculation Worsens CO, puts endothelial cells at risk of anoxic injury, Subsequent DIC Vitals organs are affected and begin to fail Clinically patient may become confused and U.O. declines

29. Unless there is intervention  process eventually enters irreversible stage Widespread cellular injury lysosomal enzyme leakage NO synthesis myocardial contractile function worsens Ischemic bowel intestinal flora can enter circulation endotoxic shock Complete renal shut down owing to ATN Despite heroic measures downward clinical spiral almost inevitably leads to death

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