1. Overview of Shock
Pathophysiology
CT1 Education Series (Intro)

3. Don’t do your research on Google!

4. What is Shock?
A severe pathophysiological insult associated with mitochondrial
and cellular energetic failure due to:
• reduced oxygen and nutrient delivery, and/or
• ineffective utilisation of oxygen and nutrients
and most often occurring in the setting of poor tissue perfusion
• Poor tissue perfusion may be absent in hyperdynamic sepsis
• Mitochondrial dysfunction is critical contributor
• This may exist with near normal perfusion and normal BP
• So…hypotension may well be present, but is not necessary

5. Determinants of effective tissue perfusion
• Cardiovascular performance
• Cardiac function & venous return
• Distribution of cardiac output
• Local tissue systems
• Sympathetic/adrenal systems
• Anatomical abnormalities
• Exogenous vasoactive agents
• Microvascular function
• Pre- & post-capillary sphincter function
• Capillary endothelial integrity
• Microvascular obstruction
• Local oxygen unloading and diffusion
• Oxyhaemoglobin affinity (RBC 2,3-DPG, pH, Temperature)
• Cellular energy generation/utilisation
• Kreb’s cycle, oxidative phosphorylation, ATP utilisation

6. Mechanisms of cellular dysfunction in shock
• Ischaemia
• Failure of ATP generation stops ion pumps, metabolism, mitochondria
• Inflammatory mediators
• TNF-α, IL-1β, IL-2, IL-6, IFN-γ, TGF-β, Endothelin-1, PAF, leukotrienes. TXA2,
prostaglandins, complement C3a, C5a
• Nitric oxide
• altered intracellular transduction
– pathological arterial and venous dilatation
– myocardial depression
• Free radical injury
• Cell membrane failure
• Gene expression patterns

7. Haemodynamic inter-relationships
Blood pressure is related to cardiac output and systemic vascular resistance
BP = CO x SVR
Cardiac output is determined by stroke volume and heart rate
CO = SV x HR
BP = SV x HR x SVR
Preload Afterload Contractility
LVEDV

8. Oxygen delivery
DO2 = SV x HR x Hb x SaO2 x 1.31DO2 = SV x HR x Hb x SaO2 x 1.31

9. Oxygen Extraction
• = arteriovenous oxygen difference
VO2 = Q × (CaO2 − CvO2)
• CvO2 equals the oxygen content of venous blood
• Oxygen extraction ratio = VO2/DO2
• Oxygen extraction ratio = SaO2 − SvO2/SaO2.
• Normal OER in humans at rest is 0.25–0.33
(assumes SvO2 65–70%).

11. Classification of Shock States
• Hypovolaemic
• Cardiogenic
• Obstructive
• Distributive
• Septic
• Neurogenic
• Anaphylactic
• Endocrine (thyroid storm, adrenal failure)

12. Defenses Against Shock
1. Maintain MAP (preload/SVR)
– Volume
• Fluid redistribution to vascular space
– from interstitium (Starling effect) [pre-capillary vasoconstriction]
– from intracellular space (osmotic effect - albumin/glucose)
• Reduce renal fluid loss
– decreased GFR
– renin-angiotensin-aldosterone
– vasopressin
• Thirst response
– Pressure
• Decrease venous capacitance
– sympathetic activity
– adrenaline/noradrenaline secretion
– angiotensin
– vasopressin

13. Defenses Against Shock
2. Maximise cardiac function
– Increase contractility
– Sympathetic stimulation
– Adrenal stimulation
3. Redistribute perfusion
– Extrinsic regulation of vascular tone
– Autoregulation of brain/heart perfusion
– Splanchnic vasoconstriction
4. Optimise O2 unloading
– RBC 2,3-DPG
– Tissue acidosis
– Pyrexia
– Tissue pO2

14. Medullary BP control & Baroreceptors

17. Organ System Consequences
CNS Encephalopathy, ischaemic necrosis
CVS Arrhythmias, ischaemia, myocardial dysfunction
RS Acute respiratory failure, ARDS
Renal Pre-renal impairment, AKI, ATN
GI Ileus, erosive gastritis, pancreatitis, acalculous cholecystitis,
bacterial translocation
Hepatic Ischaemic hepatitis (Shock liver), cholestasis, fatty liver
Haematological DIC, thrombocytopaenia, leukopaenia
Metabolic Hyperglycaemia, glycogenolysis, gluconeogenesis,
hypertriglyceridaemia, late hypoglycaemia
Immune Gut barrier dysfunction (GALT), cellular & humoral depression

18. 1. Hypovolaemic Shock

19. 2. Cardiogenic Shock
• Contributors to dysfunction
– Myocardial necrosis
• irreversible
– Myocardial stunning
• inotrope responsive
• reperfusion injury
• calcium overload
• oedema
– Hibernating myocardium
• adaption to chronic ischemia
• contractility restored by reperfusion
• Features
– PAWP > 18 mmHg
– CI < 2 L/min/m2

21. Cardiogenic Shock - Clinical
settings
• Left ventricular systolic dysfunction (the classic)
• Left ventricular diastolic dysfunction
• impaired filling and high pressures at low volumes in ischaemia or LVH
• cope poorly with tachycardia (filling worsens) or bradycardia (poor
CO)
• Valvular dysfunction
• Arrhythmias
• Right ventricular dysfunction

22. LV Pressure-volume Curves

23. LV performance curve

24. Compensatory mechanisms
• Cardiac
– Frank-Starling mechanism - the ability of the heart to change its force of
contraction and stroke volume in response to changes in venous return
– Ventricular dilation or hypertrophy
– Tachycardia
• Autonomic Nerves
– Increased sympathetic adrenergic activity
– Reduced vagal activity to heart
• Hormones
– Renin-angiotensin-aldosterone system
– Vasopressin (antidiuretic hormone)
– Circulating catecholamines
– Natriuretic peptides

25. 3. Anaphylactic Shock
• Common/clearly demonstrated:
– Fluid extravasation -> haemoconcentration & hypovolaemia
• Likely:
– Venodilation and blood pooling
– Impaired myocardial contractility
– Relative bradycardia (neurally mediated) in awake patients
– Early transient increase in pulmonary vascular resistance
– Early arteriolar dilatation [widened pulse pressure and hypotension]
– Increased SVR [increased arteriolar tone] may predominate after early phase
• Uncommon/postulated:
– Severe global myocardial depression [? stunning]
– Non-specific ST segment ECG changes (unresponsive to adrenaline)
– Severe arteriolar dilation as well as venous dilation
– Coronary ischemia caused by coronary vasospasm and plaque ulceration
COCO

26. Anaphylactic shock mediators
• Preformed mediators (immediate release)
• mast cells and basophils
• histamine, heparin, tryptase, chymase, TNF-α
• Mediators generated over minutes
• mast cells, basophils, and possibly other cells
• platelet-activating factor (PAF), nitric oxide (NO), TNF-α
• prostaglandins [PGD2] & leukotrienes [LTC4, LTD4, LTE4]
• Mediators generated over hours
• mast cells, basophils and possibly other cells
• interleukins [IL-4, IL-5, IL-13] & GM-CSF
• Other mediators
• generated by contact system activation = bradykinin, plasmin
• generated by complement pathway = anaphylatoxins C3a and C5a

27. 4. Septic Shock
• Vasodilatation
• Cytokines and PG’s -> excess nitric oxide
• Pressor resistance
– activation of KATP channel by hypoxia/acidosis/lactate
» hyperpolarised membrane = no contraction = vasodilatation
– activation of inducible NO synthase -> excess NO
– decreased circulating vasopressin levels
• Maldistribution of blood flow
• Endothelins -> pathological regional vasoconstriction
• Microvascular occlusion by WBCs and thrombus
• Protein C deficiency
• Myocardial depression
• TNF-α & IL-1β -> altered β receptor signal transduction
• Uncontrolled immune response then ? paresis

29. Protein C Deficiency in Septic
Shock

30. 5. Pericardial Tamponade
Clinically or physiologically significant compression of
the heart by accumulating pericardial contents,
including effusion fluids, blood, clots, pus, and gas,
singly or in combination
• As little as 100ml of fluid if rapid onset
• > 1L of fluid if slow onset

32. Defences against tamponade
1. Pericardial reserve volume
2. Pericardial stretch
3. Increase (venous) blood volume
When defences overwhelmed…
• Reduced cardiac inflow
• Chamber compression (RA & RV first)
• Diastolic compliance falls – pressure rises
• Diastolic pressures equalise
• Stroke volume falls
• Initial compensation then sudden catastrophic decline

33. Pulsus paradoxus
• Accentuated decrease in BP during inspiration
• Normal is < 10 mmHg
• Radial pulse may be lost
• Inspiration causes negative intrathoracic pressure
– Increased right heart filling
– Pooling of blood in pulmonary veins
– Shift of septum into LV (RV free fall can’t expand)
– Reduced LV filling (preload) and stroke volume

34. Pulsus Paradoxus

35. Pericardial Tamponade

36. 6. Pulmonary Embolism
• Haemodynamic response depends on:
– Size of embolus
– Baseline cardiopulmonary function
– Neurohumeral effects
• Serotonin from platelets
• Thrombin from plasma
• Histamine from tissue

37. Pulmonary Embolism
• Increased pulmonary vascular resistance
• Vascular outflow occlusion by thrombus
• Hypoxic pulmonary vasoconstriction
• PA pressure may double to > 40 mmHg in the healthy
• Increased RV afterload
• => RV dilatation
• => Hypokinesis
• => Tricuspid regurgitation
• RV dilatation
• => Shift of interventricular septum to left
• => Diastolic LV impairment & reliance on LA “kick”
• Ischaemia
• RCA compression due to increased RV wall tension
• Hypoxaemia
Eventual
RV Failure
(12-48hrs)
Eventual
RV Failure
(12-48hrs)

38. Management Approach