Pathophysiology of circulatory shock Prof. MUDr. Miloš Tatár, CSc. Dept of Pathophysiology

Clinical features of shock - drop of systolic blood pressure (BP  90 torr) in hypertonic patients: decrease of 50 torr - low cardiac output and tachycardia - vasoconstriction: skin and splanchnic areas - oliguria (< 20 ml/hour) - cold wet skin - constriction of superficial veins - marked muscle weakness - usualy  body temperature (except septic shock) - disorientation - metabolic acidosis

Characteristics of circulatory shock Complex clinical syndrome encompassing a group of conditions with variable hemodynamic manifestations Common denominator is generalised inadequacy of blood flow through the body; hypoperfusion compromises the delivery of oxygen and nutrients and the removal of metabolites; tissue hypoxia shifts metabolism to anaerobic pathways with production of lactic acid if shock is not corrected it leads to: a) cell dysfunction b) irreversible multiorgan insufficiency d) death

Cardiovascular dysorders in shock: a) acute circulatory insufficiency b) mismatching between blood volume and volume of vascular bed tissue hypoperfusion

Blood pressureTissue perfusion Cardiac output x Vascular resistance

Factors determining tissue perfusion A. cardial: A. cardial: cardiac output B. vascular: B. vascular: changes in vascular resistance regulation of vascular tone: regulation of vascular tone: - tonic sympathetic activity - systemic catecholamines - myogenic response - constant tissue blood flow during changed perfusion pressure - metabolic autoregulation - vasodilatory substances - endothelial NO

C. humoral C. humoral: renin, vazopresin, prostaglandins, kinins, atrial natriuretic factor Factors determining microcirculation: - adhesion of leukocytes and platelets on epithelial lesions - intravascular coagulation - constriction of precapillary and postcapillary vessels - intense hypoxia  vasodilation of arteriols, venoconstriction continues  intravascular fluid loss -  capillary permeability  tissue edema

Etiology of circulatory shock 1. Hypovolemic - intravascular fluid volume loss hemorrhage, fluid depletion or sequestration 2. Cardiogenic- impairment of heart pump 2. Cardiogenic - impairment of heart pump myopathic lesions: myocardial infarction, cardiomyopathies dysrhythmias obstructive and regurgitant lesions of intracardial blood flow mechanics

3.Obstructive factors extrinsic to cardiac valves and 3. Obstructive - factors extrinsic to cardiac valves andmyocardium v. cava obstruction, pericardial tamponade, pulmonary embolism, coarctation of aorta 4.Distributive pathologic redistribution of intravascular 4. Distributive -pathologic redistribution of intravascular fluid volume septicaemia: endotoxic, secondary to specific infection anaphylactic

NORMAL 1. HYPOVOLEMIC 2. CARDIOGENIC 3. DISTRIBUTIVE High Resistance 4. OBSTRUCTIVE Low Resistance

Pathogenesis of circulatory shock inadequate cardiac output (CO) Usually results from inadequate cardiac output (CO) Any factor reducing CO will likely lead to shock 2. Decreased venous return - diminished blood volume - decreased vasomotor tone fl - obstruction to blood flow at some points in the circulation 1.Cardiac abnormalities decreased ability of the heart to pump blood - myocardial infarction - toxic states of heart - severe heart valve dysfunction - arrhythmias

Stages of shock 1. Nonprogressive stage (compensated) (negative feedback) Compensatory mechanisms (negative feedback) of the circulation can return CO and BP to normal levels - baroreceptor reflexes protection of coronary and cerebral blood flow - baroreceptor reflexes  sympathetic stimulation  constrict arteriols in most parts of the body and venous reservoirs  protection of coronary and cerebral blood flow - angiotensin-aldosteron, ADH - angiotensin-aldosteron, ADH  vasoconstriction, water and salt retention by the kidneys - absorption of fluid from ISF and GIT, increased thirst

2. Progressive shock - positive feedback mechanisms - positive feedback mechanisms are developed and can vicious circle cause vicious circle of progressively decreasing CO - circulatory system themselves begin to deteriorate, without therapy shock becomes steadily worse until death Cardiac depression Cardiac depression -  coronary blood flow,  contractility Vasomotor failure - Vasomotor failure -  cerebral blood flow Release of toxins by ischemic tissues: Release of toxins by ischemic tissues: histamine, serotonin, tissue enzymes Intestines hypoperfusion  mucosal barrier disturbance endotoxin  endotoxin formation and absorption  vasodilatation, cardiac depression Generalised cellular deterioration Generalised cellular deterioration:  K +,  ATP, release of hydrolases – first signs of multiorgan failure Vasodilation Vasodilation in precapillary bed

3. Irreversible shock - despite therapy circulatory system continues to death ensues deteriorate and death ensues - marked hypoxic tissue damage - endothelial dysfunction  adhesive molecules, inflammation neutrophils, macrophages  inflammation - progressive acidosis - advanced disseminated intravascular coagulation - microcirculation failure  plasma proteins leak to interstitium

Cardiogenic shock - ventricle fails as a pump - infarction process (45% loss of functional mass of left ventricle) - BP  90 torr for at least 30 min,  pulmonary capillary pressure  lung edema (vicious circle) metabolic acidosisreduced coronary perfusion dysrhythmias - self-perpetuing cycle then ensues (vicious circle): metabolic acidosis and reduced coronary perfusion further impairing ventricular function and predisposing to the development of dysrhythmias Progression of myocardial dysfunction: - hypotension, tachycardia, fluid retention, hypoxemia

Septic shock Typical causes: Typical causes: peritonitis, gangrenous infection, pyelonephritis Special features: 1. high fever 2. marked vasodilatation (inflammation) 3.  or normal CO: vazodilatation,  metabolic rate 4. disseminated intravascular coagulation  clotting factors to be used up  hemorrhages occur into many tissue (GIT) IL-1 and TNF: PGE 2, leukotrienes and NO - vascular relaxation -  endothelial permeability (deficit of intravascular volume) -  myocardial contractility

Early stage: Early stage: no signs of circulatory insufficiency Progression of infection: Progression of infection: circulatory disorders becomes  deterioration of circulation  Bacterial toxins  deterioration of circulation  end-stage is not greatly different from the end-stage (hypodynamic stage) of hemorrhagic shock (hypodynamic stage) Death: - Death: - hypotension - multiorgan failure

Cell dysfunction cell death prolong tissue hypoperfusion  cell membrane lesion, lysosomal enzymes  cell death mechanisms: mechanisms: hypoxia, inflammatory mediators, free radicals

Multiorgan failure Kidney oliguria -  blood flow (to 10%)   GF  oliguria acute tubular necrosis - ischemia  acute tubular necrosis izostenuria - countercurrent mechanism failure  izostenuria acute renal failure - marked lesions  acute renal failure

Lungs - disturbances of pneumocytes and endothelium - accumulation of Tr, Neu in pulmonary circulation  release of proteases -  leukotriens and free radicals -  permeability -  surfactant, edema and hemorrhagies respiratory insufficiency(ARDS)  respiratory insufficiency (ARDS)

% SURVIVAL ( 142 Pts) > 16 LACTATE mM/l

HYPOVOLEMIC EXTRACARDIAC Obstruction CARDIOGENICDISTRIBUTIVE Fluid loss, hemorrhage e.g., Pericardial tamponade Myocardial injury or necrosis Decreased systemic vascular resistance Myocardiac dysfunction Reduced systolic performance Reduced filling Low cardiac output Reduced preload Decreased arterial pressure Shock Multiple organ system failure High or normal cardiac output Maldistribution of blood flow in microcirculation