Physiology of shock

1. Late Sciences lecture series: Lecture 1 Physiology of shock Mahesh Nirmalan Division of Cardiovascular Sciences Intensive Care Unit, Manchester Royal Infirmary

2. Objectives • Definition • Clinical end points • Classification • Stages • Physiological compensation • Immediate • Late • Treatment objectives

3. MCQ: Shock is defined as: • Sustained reduction in Systolic blood pressure < 80 mm Hg • Sustained reduction in mean arterial pressure < 80 mm Hg • Sustained reduction in diastolic blood pressure < 40mm Hg • Inadequate blood flow to the tissues to meet its metabolic requirements • None of the above

4. MAP= 68 mm Hg MAP= 90 mm Hg Compensated shock MAP is a very poor surrogate of blood flow to the peripheral tissues Vasoconstriction will maintain MAP at thee expense of tissue flow Compensated shock

5. Definition of Shock Shock is an acute clinical syndrome initiated by ineffective perfusion, resulting in severe dysfunction of organs vital to survival. Shock is not a synonym to hypotension!

6. Shock: Definition • Inadequate perfusion to tissues • Large enough to compromise the supply of nutrients and removal of metabolic waste • Resulting in compromised organ functions • Usually recognised by clinical features suggestive of reduced blood flow • Reduced capillary fill • Cold clammy hands or feet • Widening core-toe temperature gradient • Reduced urine output • Raised plasma [Lactate-] • Low blood pressure is a late sign- particularly in the young previously fit individuals

7. Hypovolaemia Cardiogenic shock Obstructive Sepsis Anaphylaxis Ineffective perfusion Organ perfusion may be compromised by an overall decrease or maldistribution of cardiac output.

8. Classification • Hypovolaemic: Haemorrhage, loss of ECF • Cardiogenic: Tamponade, Infarction, heart failure • Extracardiac obstructive: Pulmonary embolism, tension pneumothorax • Distributive: sepsis, anaphylaxis

9. Physiological factors affecting Arterial pressure, CO and ventricular performance

10. Blood volume Venous tone RA pressure Intra-pleural pressure Ventricular filling: preload State of myocardium pH Inotropic state Catecholamines, sympathetic tone SV Contractility Arteriolar tone Catecholamines Sympathetic tone After load SV* HR=CO Systemic vascular resistance Arteriolar tone Catecholamines Sympathetic tone Arterial pressure

11. Effect of EDV and contractility on SV

12. Stages of shock • Compensated shock or occult shock • Normal physiological compensation will lead to complete recovery • External interventions not necessary • Progressive shock • Progressively worse in the absence of external interventions • Irreversible shock • Death is inevitable in spite of all forms of therapy

13. Stages of shock • Compensated shock • Autotransfusion • De-compensated shock • Redistribution of blood • Irreversible shock • MODS/ delayed death

14. CO, MAP and SvO2

15. Post hoc groups Irreversible shock Plasma [Lactate] A priori groups 6 C(n=9) S(n=10) 5 G(n=10) 4 Plasma[lactate] (mmol/l) 3 2 1 0 Baseline Initiation of End of shock Post shock phase phase resuscitation

16. Effects of prolonged shock on cardiac functions • Modified Frank- Starling curves • Dogs bled to a pressure of 30mm Hg • Maintained hypotensive for variable periods • Resuscitated in stages to assess ventricular functions • Impaired ventricular functions after 4 hours of sustained shock • Concept of irreversible shock CO 0 5 10 LAP mm Hg Adapted from Crowell et al 1962

17. Reversible Vs Irreversible shock Sustained shock can breed more shock Adopted from Guyton and Hall

18. Physiological compensatory mechanisms • Immediate • Fluid shifts • Neural reflexes: Autonomic nerves • Endocrine • Delayed • Renal: Renin-Aldosterone-Angiotensin • Hypothalamo-pituitary axis • ADH • Thirst

19. Starling Forces at the capillary bed Net Filtering Pressure = +5 mmHg Net Filtering Pressure = - 5 mmHg Hydrostatic Pressure= 0 mmHg Interstitial Fluid Venous end Arterial end Blood Hydrostatic Pressure = 30 mmHg Colloid Osmotic Pressure= 25 mmHg Hydrostatic Pressure = 20 mmHg In the normal microcirculation   - At arterial end: water moves out of the capillary Hydrostatic pressure > COP - At venous end: water moves into the capillary Oncotic pressure > Hydrostatic pressure

20. Compensation in shock • In shock, the hydrostatic pressure decreases and the oncotic pressure is constant • The fluid loss from the capillary to the extracellular space decreases. • Re-absorption of fluid return from the extracellular space increases • Partially compensates for the loss in circulatory volume • Never complete • “Fluid shift system” • Re-absorption is aided by the increase in osmotically active substances in blood: Glucose • The amount of fluid recruited through the metabolic responses may be substantial: 20-30m Osmol: 0.5 liters of fluid • Hyperglycaemia is an evolutionary survival mechanism • When persistent may have adverse consequences

21. Venoconstriction: autotransfusion Vasoconstriction: redistribution Tachycardia Increased rate and force of contraction Autonomic neural reflexes • Baro-receptors mediated increase in sympathetic outflow • Chemo-receptor mediated sympathetic outflow • Ischaemic brain response: Late but powerful

22. Ischaemic brain response Stages of shock • Compensated shock • Autotransfusion • De-compensated shock • Redistribution of blood • Irreversible shock • MODS/ delayed death

24. Autonomic reflex responses to hypovolaemia • Baroreceptors are stimulated by stretch: MAP and pulse pressure • Sympathetic outflow is inhibited by baroreceptor affarents • Direct as well as via the vagal nucleus • Reduction in baroreceptor affarents therefore lead to vasoconstriction and tachycardia • Compensates for reduction in MAP and pulse pressure

25. Chemo-receptors • Central chemo-receptors: Medulla • Peripheral chemo-receptors: Carotid body and aortic body • Particularly relevant when MAP < 60 • H+ and CO2 • Evoke a powerful sympathetic response

26. Sympathetic responses to haemorrhage and shock • In the absence of sympathetic responses 15-20% acute haemorrhage is usually fatal. • In the presence of an intact sympathetic response patients may be able to tolerate 30-40% acute haemorrhage and recover completely • Venoconstriction is helpful in maintaining stroke volume • Arterial constriction maintains blood pressure at the expense of organ blood flow • Aimed at preserving coronary and cerebral perfusion • Minimal constriction of the coronary and cerebral vessels • Does not fall until systolic pressure is < 70 mm Hg • Prolonged arterial-constriction initiates secondary changes in organ function

27. The early compensatory mechanisms preserve arterial pressure at the expense of blood flow to key visceral organs

28. Progressive and non-progressive shock

29. Multiple organ failure Generalised cellular degeneration • Prolonged lack of oxygen and nutrients affect the viability of organs • Tissues with high metabolic activity are more prone • Centri-lobular necrosis of the liver • Na+/K+ active transport→swelling • Mitochondrial activity depressed • Release of lysosomal hydrolases • Interruption of metabolism • Lungs • Heart • Gut mucosal barrier Patients resuscitated after prolonged shock usually die of multiple organ failure Human and Health care costs

30. Delayed compensatory pathways Restores normalcy

31. Treatment priorities in shock • Use of inotropic agents to restore myocardial contractility • Use of vasoactive drugs to cause venoconstriction, vasoconstriction and thereby restore venous return and blood pressure • Restore circulating blood volume to optimise cardiac functions • Increase heart rate to increase cardiac output • Use of HCO3- to prevent metabolic acidosis

32. Myocardial O2 supply Myocardial O2 demand Tachycardia, though an important compensatory mechanism always comes at a price Heart rate Wall tension After load CPP Diastolic time CO O2 content

33. Questions?