1、Circulatory shock (hypoperfusion),syndrome,Basal pathogenetic mechanisms of circulatory shock2. Changes in macro- and microcirculation3. Shock mediators4. Types of shock syndrome5. Derangements of organ functions multiple organ failure (MOF)6. Shock dynamics7. Clinical expression of shock8. Shock th
2、erapy,1. Basal pathogenetic mechanisms of shock,Definition of circulatory shock: An acute dysbalance between delivery and consumption of oxygen in all (or all vital at least) organs, which cannot be compensated for (or only transitorily)Dynamics: generalization, self-maintainance, refractoriness,Tis
3、sue ischemia could be produced by:-decline of circulating volume (haemorrhagic shock)-failure of cardiac performance (cardiogenic shock)-failure of regulation of peripheral resistance relative lack of volume and/or of exchange area of capillaries (anaphylactic shock, septic shock),Hypotension is typ
4、ical, however, normotonic phases may be present-regulatory reaction (sympatoadrenal system, glucocorticoids, vasopressine, endorphins)-endotoxin hyperdynamic shock syndrome“,2.Changes in macro- and microcirculation,Excessive activity of sympatoadrenal system,catecholamine concentration tachycardia,
5、contractility of myocardium, vasoconstriction, tonisation of capacitance vessels venous return centralisation of circulation (for the benefit of heart and brain) long-term organ dysfunction (kidneys!),Specific microcirculatory and vasomotoric disturbance,Fig. 1 Vasomotorics and fluid exchange in sho
6、ck:1 - normal 2 - sympaticus precapillary vasoconstriction tissue perfusion sucking of fluids hematocrit, blood viscosity, plasma oncotic pressure dissociation of capillary regions:-stasis-fast streaming plasma poor in cells unbalanced capillary perfusion perfusion per unit area 3 - tissue acidosis
7、dilation of precapillary sphincters extravasation hemoconcentration (+ edema) perfusion,1,3. Shock mediators,Kallikrein-kinin systeme:,Kininogens in plasma (HMWKG and LMWKG) cleaved by kallikrein (plasma and tissue) bradykinin (=kinin 9) and kallidin (= kinin 8) BP, contraction of extravascular smoo
8、th musculature, vasodilation and permeability, pain,Contact activation: Complex of prekallikrein + HMW-kininogen + Hageman factor (XII) present in plasma affinity to negatively charged surfaces addition to them mutual activation of Hageman factor and prekallikrein rise of kinin permeability etc. ris
9、e of plasmin fibrinolysis activation of the intrinsic pathway of blood clotting (coagulation),In shock the following systems are activated (Fig. 2):- blood clotting stasis, acidosis, effusion of tissue factor (in traumas)- complement immunocomplexes, plasmin, thrombin etc.- kallikrein-kinin Hageman
10、factor; effects as above- arachidonic acid Endo- + exotoxins of bacterias role in septic shock syndrome,2,In all forms of shock, releasing of cytokines and other mediators influencing the vasculatory tonus is of basal importance:- Aggregated platelets thromboxan A2, serotonin, leucotriens, reactive
11、oxygen species- Adhering and activated leucocytes thromboxan A2, PGE2, PAF, ROS, proteases- Damages endothelial cells PGI2, thromboxan, PAF, HETE, interleukin-1, ROS- Macrophages TNF vascular resistence and BP,Reperfusion damage Shock therapy (xanthindehydrogenase xanthioxidase) rise of ROS lipid pe
12、roxidation rise of AA metabolites and denaturation of cellular (incl. membrane) proteins endothelial lesions, intracellular edema, inflow of calcium ions into cells cellular necrosisHypoperfusion production and metabolism of lactic acid tissue acidosis,4. Types of shock syndrome,Hypovolemic shock,De
13、finition: A shock caused by decline of intravascular volume (acute loos of 20-30% of volume) insufficient preload cardiac output: Q = P/ R (Fig. 3). Administration of fluids () restauration of CO Traumatic shock: extensive tissue lesions, of volume. Early stimulation of humoral cascades, nociceptors
14、 sympatoadrenal reaction,Cardiogenic shock,Definition: A shock caused by all types of cardiac failure, inclusive by cardiac tamponade, pneumo- and hemothorax and pulmonary embolism. Preload is adaequate, in spite of this, CO is insufficient: Q = P/R (Fig. 4) Diagnosis must prove the adaquate preload
15、,Distributive = vasodilatory = vasogenic = hyperdynamic shock,Definition: Shock produced by loss of regulation of peripheral resistance relative lack of volume + decline of exchange area of capillary bed (Fig. 5) Inappropriate vasodilation peripheral amassing of blood preload compensatory rise of co
16、ntractility (hyperdynamic circulation“); CO may be high, normal od decreasedEtiology: sepsis, anaphylaxis, CNS depressionCombined shock syndromes are common,Disturbances of organ functions multiple organ failure (MOF),Focal ischemia, activation of humoral systems (esp. of complement s.), interaction
17、 of leucocytes with endothelial cells progressing disturbance of perfusion and function of organs. Cytokines (esp. IL-1 a TNF) stimulate granulocytes (ROS, adhesion to endothelial cells, cytotoxicity). MOF could be invoked by sole cytokine infusion. It appears after lag of hours to days Pulmonary fa
18、ilure (shock lung“),Pulmonary permeability edema: - Initial phase: intrapulmonary blood volumen (not in cardiogenic shock!), collaps of alveoli in dependent regions ventilation-perfusion ratio (functional shunt)- Adult respiratory distress syndrome:- Exsudative phase- Early proliferative phase: fibr
19、in and leucocytes in interstitial and alveolar spaces- Late proliferative phase: fibroblasts and histiocytes, thickening of alveolar septaPulmonary functions: progressing hypoxemia, pulmonary compliance, dynamic pulmonary resistencies, mechanical work,Renal failureIschemic damage and/or compensatory
20、 mechanism diuresis. Sympatoadrenal stimulation renal perfusion. Prerenal azotemia, later acute tubular necrosisHepatic failureLowering of syntheses in the liver (clotting factors!), lowering of the trapping liver capacity for some metabolites (lactate!)Storage of glycogen exhausted soon therapetic
21、delivering of energy“cleaning“ function of the system of mononuclear phagocytes accumulation of vasoactive and clotting promoting metabolites disseminated intravascular coagulation spill-over“ of bacterias and endotoxins into systemic circulation,Gastrointestinal failureDisturbances if microcirculat
22、ion and focal ischemia permeability of gut vessels leakage of fluid rich in proteins into interstitium loss of circulating volume intu gut lumen and peritoneal cavity accentuation of hypovolemia. Corruption of mucosal barrier bacteriemia, sepsis,Stages of shock (Fig. 6 : I. early, latent“ stage, com
23、pensated“ shock; II. progressive“, decompensated“ shock; III. irreverzible“, refractory“shock,6,Compensated shock: blood pressure and CO may be normal. Extremely labile stage, weight of the situation may go unnoticed Progressive (decompensated) stage: positive feebacks spontaneous“ deepening of shoc
24、k. BP, CO, ARDS and oliguria,metabolic acidosis (!) Irreversible (refractory) shock: no therapeutic measure can avoid progressive worsening. Steady decline of CO, BP, acidosis. Koma and reanal failure with uremia.,Fig 7 Positive feedback in a progressive shock,7,Fig. 8 Synopsis of pregressive shock,Fig. 9 Irreversible shock,7. Shock therapy,Fig. 10 Normal pressures in cardiac chambers,
