Shock pathophysiology

Overview of Shock Pathophysiology

CT1 Education Series (Intro)

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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

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

Mechanisms of cellular dysfunction in shock

• Ischaemia• Failure of ATP generation stops ion pumps, metabolism, mitochondria

• Inflammatory mediators• TNF-, IL-1, IL-2, IL-6, IFN-, TGF-, 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

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 SVRPreload Afterload Contractility LVEDV

Oxygen delivery

DO2 = SV x HR x Hb x SaO2 x 1.31

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%).

Classification of Shock States• Hypovolaemic• Cardiogenic• Obstructive• Distributive

• Septic• Neurogenic• Anaphylactic• Endocrine (thyroid storm, adrenal failure)

Defenses Against Shock1. 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

Defenses Against Shock2. 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

Medullary BP control & Baroreceptors

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

1. Hypovolaemic Shock

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

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

LV Pressure-volume Curves

LV performance curve

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

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

CO

Anaphylactic shock mediators• Preformed mediators (immediate release)

• mast cells and basophils

• histamine, heparin, tryptase, chymase, TNF-

• Mediators generated over minutes• mast cells, basophils, and possibly other cells

• platelet-activating factor (PAF), nitric oxide (NO), TNF-• 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

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- & IL-1 -> altered receptor signal transduction

• Uncontrolled immune response then ? paresis

Protein C Deficiency in Septic Shock

5. Pericardial Tamponade

Clinically or physiologically significant compression ofthe 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

Defences against tamponade1. Pericardial reserve volume2. Pericardial stretch3. 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

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

Pulsus Paradoxus

Pericardial Tamponade

6. Pulmonary Embolism

• Haemodynamic response depends on:– Size of embolus– Baseline cardiopulmonary function– Neurohumeral effects

• Serotonin from platelets• Thrombin from plasma• Histamine from tissue

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)

Management Approach