Pathophysiology of circulatory shock Shock - definition —Severe tissue hypoperfusion resulting in low supply of oxygen to the organs —Systemic hypotension (of various causes) is present —P = Q ´ R —Q ~ CO = SV ´ f —CO depends on — a) cardiac function — b) venous return (→preload) •R – systemic resistance (mostly arterioles) - afterload Cardiac function and venous function —aa Phases of shock —Compensation of initiating cause —Decompensation —Refractory shock Compensatory mechanisms and their limits —Activation of sympathetic nervous system (tens of seconds) —Activation of RAAS (cca 1 hour) —Vasoconstriction (if possible) —Vasodilatation in some tissues (esp. myocardium) —Positively inotropic effect of SNS (if possible) – but at cost of higher metabolic requirements of the heart —Increased heart rate – but CO decreases in high HR (>150 bpm) —Keeping circulating volume by lower diuresis – but at cost of acute renal failure —Shift to anaerobic metabolism – but at cost of ↓ ATP a ↑ lactate (acidosis) —Shift of saturation curve of hemoglobin to right (↑2,3-DPG) —Hyperglycemia – but there is decreased utilization of Glc in the periphery — — — http://pfyziollfup.upol.cz/castwiki2/wp-content/uploads/2011/07/Frekv.jpg Heart rate [min-1] Decompensated shock —↓ BP —↓ diuresis —Brain hypoperfusion – involvment of mental functions —Acrocyanosis —Tachypnoe —Treatment – colloid solutions, catecholamines Shock at cellular level —Mitochondrial dysfunction (result of hypoxia) – lower production of ATP —↑ ROS production by dysfunctional mitochondria —Failure of ion pumps (e.g. Na/K ATP-ase →↑intracelular Ca2+) —Lysosomal abnormalities – release of lysosomal proteases —↓ intracelular pH Refractory shock —Vicious circles — 1) Vasodilatation ↔ hypoperfusion ◦Endothelial cells contain two isoforms of nitric oxid synthase – constitutive (eNOS) and inducible (iNOS) ◦In lasting hypoxia of endothelial cells there is increased iNOS activity (primarily physiological mechanism) ◦↑NO increases vasodilation and hypoperfusion ◦2) Myocardial hypoxia ↔ lower contractility ◦Lower myocardial perfusion leads into ↓CO, which further reduces coronary flow ◦Myocardium does not benefit from the shift of Hb saturation curve – efficiency of O2 extraction is already at its maximum ◦3) Brain hypoperfusion ↔ ↓SNS activity ◦Lower perfusion of vasomotor centre leads first into SNS hyperactivity, which is then followed by its supression ◦That leads into ↓brain perfusion ◦ Other vicious circles in refractory shock http://emsbasics.com/files/2011/12/img00005.gif Forms of shock a)Hypovolemic shock (i.e. absolute fluid loss) – low preload b)Distributive („warm“) shock – low resistance, afterload, CO might be increased c)Cardiogennic shock – normovolemia, normodistribution, low CO in bad cardiac function d)Obstructive shock – low preload of one ventricle in normovolemia and subsequent lowering of CO – pathophysiology similar to cardiogennic shock e) Cardiac and venous function in shock —Hypovolemic shock: compensation by the vasoconstriction and cardiac mechanisms —Distributive shock: compensation by cardiac mechanisms (vasoconstriction is usually impossible) —Cardiogennic (and obstructive) shock: compensation by vasoconstriction Q [dm3.min-1] P [mmHg] in right atrium http://o.quizlet.com/i/E7P6z4XySta1htzMfDHg1A.jpg Hypovolemic shock - causes —Acute bleeding —Burns, trauma —Rapid development of ascites —Acute pancreatitis —Severe dehydratation ◦Vomiting, diarrhoea ◦Excessive diuresis (e.g. in diabetes insipidus) Distributive shock - causes —Anafylactic shock —Anafylactoid shock ◦Mediators of mast cells, but without IgE ◦E.g. snake venoms, radiocontrasts —Septic shock ◦Role of bacterial lipopolysaccharides ◦Bacterial toxins ◦IL-1, TNF-α – stimulate synthesis of PGE2 and NO —Neurogennic shock ◦Vasodilatation as a result of vasomotoric centre (or its efferent pahways) impairment Cardiogennic shock - causes —Myocardial infarction —Arrhythmias —Valvular disease (e.g. rupture of papillary muscles) —Decompensation of heart failure in dilated/restrictive cardiomyopathy, amyloidosis —Overload by catecholamines (“tako-tsubo cardiomyopathy“ – apical akinesia + basal hyperkinesia) — — —Rupture of ventricular septum —Obstructive shock – e.g. cardiac tamponade, massive pulmonary embolism, aortic dissection https://encrypted-tbn0.gstatic.com/images?q=tbn:ANd9GcQQtSiuL07uDaZxA4jCasQ6j7GWaWKJJ7JfAzWg7AsOFAD IugPUIQ Organ complications in shock —Lungs ◦ARDS —Liver ◦necrosis of hepatocytes —GIT ◦stress ulcer ◦Damage of intestinal mucosa by ischemic necrosis → sepsis —Kidneys ◦Acute renal failure in vasoconstriction of a. afferens ◦Acute tubular necrosis during ischemia — Disseminated intravascular coagulopathy (DIC) —Systemic exposure to thrombin —Consequence of the vessel wall damage —Moreover, slower blood flow contributes to the extent of coagulation reactions —Two phases: 1)Formation of microtrombi (with local ischemia) 2)Bleeding as a result of consummation of coagulation factors —DIC is especially frequent in septic shock http://www.impact-r.com/en/wp-content/uploads/2012/01/bloodclot.png Systemic Inflammatory Response Syndrome(SIRS) —Systemic activation of immune mechanisms —Causes: ◦infections (sepsis) ◦Shock caused by non-infectious causes (diffuse tissue damage in hypoxia) ◦Non-compatible blood transfusions ◦Radiation syndrome (esp. GIT form) Adult Respiratory Distress Syndrome (ARDS – „shock lung“) —Result of lung inflammation in SIRS, pulmonary infections, aspiration of gastric juice, drowning —Exsudative phase (hours): cytokine release, leukocyte infiltration, pulmonary edema, destruction of type I pneumocytes —Proliferative phase: fibrosis, ↑ dead space, proliferation of type II pneumocytes —Reparative phase: ↓ inflammation, ↓ edema, continuing fibrosis, in most cases permanent restrictive diseases — http://classconnection.s3.amazonaws.com/445/flashcards/491445/jpg/ards_clinical_pathology1318419263 671.jpg Multiorgan dysfunction syndrome (MODS) —Failure of more organs at once (lungs, liver, GIT, kidneys, brain, heart) —It can develop after initial insult (days or weeks) —Hypermetabolism, catabolic stress —Can both preceed or result from SIRS General principles of treatment —Treatment of underlying cause —Positively inotropic drugs, vasopressors (e.g. catecholamines – but: they can worsen the situation in obstructive shock) —Colloid solutions, crystaloid solutions (but: there is a risk of edema in cardiogennic shock) —O2 —i.v. corticoids (anafylaxis, SIRS?) —ATB (septic shock) —Mechanic circulation support (cardiogennic shock) —Anti-shock position