What is Shock????• Profound hemodyamic and metabolicdisturbance characterized by failure of thecirculatory system to maintain adequateperfusion of vital organs.• Normal relationship between oxygen demandand oxygen supply is impaired.
Etiology of circulatory shockReduced cardiac outputHypovolaemic shock• Reduction in circulating volume causing a reduction in venousreturn and consequential reduction in cardiac output• haemorrhage• DehydrationObstructive shock• Mechanical obstruction to normal venous return or cardiacoutput• massive pulmonary embolism• tension pneumothorax• cardiac tamponade
Low peripheral resistanceDistributive shock• Peripheral vasodilatation – may be associated withinadequate increase in cardiac output• septic shock• anaphylaxis• neurogenicEndocrine shock• Addisonian crisis• Hyper/hypothyroid crisis
Stages of shock• Nonprogressive stage (sometimes called thecompensated stage) - normal circulatory compensatorymechanisms eventually cause full recovery withouthelp from outside therapy.• Progressive stage - without therapy, the shockbecomes steadily worse until death.• Irreversible stage - shock has progressed to such anextent that all forms of known therapy are inadequateto save the person’s life, even though, for the moment,the person is still alive.
What makes the shock to go into compensatedor decompensated state???• Depends on the feedback mechanism elicited by theshock• Can be negative feedback mechanism or positivefeedback mechanism.• Negative feedback predominant – compensdatedstage of shock• Termed negative because the direction of thesecondary change in response to shock is opposite tothe direction of the initiating change
• Positive feedback mechanisms exaggerate anyprimary change initiated aggravating the hypotensioninduced by shock and tend to initiate "vicious"cycles, which may lead to decompensated orirreversible stage.• Whether a positive feedback mechanism will lead toa vicious cycle depends on the gain of thatmechanism.• Gain is defined as the ratio of the secondary changeevoked by a given mechanism to the initiatingchange itself.• A gain greater than 1 induces a vicious cycle; a gainless than 1 does not
Non progressive or compensated shockNegative feedback mechanism responsible fornon progression of shock includes: Baroreceptor reflexes –• elicit powerful sympathetic stimulation of the circulation.• Generalized arteriolar constriction is a prominent response to thediminished baroreceptor stimulation• The reflex increase in peripheral resistance minimizes the fall inarterial pressure caused by the reduction of cardiac output.• Vasoconstriction most pronounced in the cutaneous, skeletalmuscle and splanchnic vascular beds, slight or absent in thecerebral and coronary circulations.• Renal vasoconstriction resisted by autoregulatory mechanisminitially but with severe shock there occurs intense renal andsplanchnic vasoconctriction.
Chemoreceptor reflexes.• Reductions in arterial pressure below about 60 mm Hg do not evokeany additional responses through the baroreceptor reflexes.• Inadequate blood flow hypoxia in chemoreceptor tissues andactivation of chemoreceptor reflex. CNS ischaemic response.• Fall in Mean Arterial Pressure below 50 mm hg activates the response.• The sympathetic nervous discharge is several times greater than themaximal neural activity that occurs when the baroreceptors cease to bestimulated.• With more severe degrees of cerebral ischemia, however, the vagalcenters also become activated. Reverse stress-relaxation of the circulatory system,• causes the blood vessels to contract around the diminished bloodvolume, so that the blood volume that is available more adequately fillsthe circulation.
Formation of endogenous vasoconstrictors.• Epinephrine from the adrenal medulla, whereas norepinephrine from boththe adrenal medulla and the peripheral sympathetic nerve endingsreinforce the effects of sympathetic nervous.• Vasopressin , a potent vasoconstrictor, is actively secreted by theposterior pituitary gland.• The plasma concentration of vasopressin rises progressively as thearterial blood pressure diminishes. The receptors responsible for theaugmented release of vasopressin are the sinoaortic baroreceptors andstretch receptors in the left atrium.
• Diminished renal perfusion during shock secretion of renin fromthe juxtaglomerular apparatus conversion of angiotensinogen toangiotensin I ACE converts angiontensin I to angiotensin II.• Angiotensin II is a powerfull vasoconstrictor. Compensatory mechanisms that return the blood volume backtoward normal.• Absorption of fluid into the blood capillaries from the interstitial spacesof the body.• conservation of water and salt by the kidney by release of aldosterone.• increased thirst and increased appetite for salt, which make the persondrink water and eat salty foods if able.
Progressive stage of shock• Caused by a vicious circle of cardiovasculardeterioration.• Positive feedback mechanism evoked byuncorrected shock results in the vicious progression.• Requires prompt and aggressive intervention elsethe shock enters the irreversible stage where deathis imminent
• Different types of “positive feedback” that can lead to progression ofshock. (courtesy- guyton n hall textbook of physiology 11th edition
Cardiac depression.• blood pressure coronary blood flow hypoxia and decreasenutrition of myocardium leading to diminshed contractility and reducedcardiac output.• The consequent reduction in cardiac output leads to a further decline inarterial pressure, a classic example of a positive feedback mechanism• The role of cardiac failure in the progression of shock duringhemorrhage is controversial.• The reduced blood flow to the peripheral tissues leads to anaccumulation of vasodilator metabolites which decreases peripheralresistance and therefore aggravates the fall in arterial pressure• All investigators agree that the heart fails terminally, but opinionsdiffer about the importance of cardiac failure during earlier stages ofhemorrhagic hypotension.• The heart has tremendous reserve capability that normally allows it topump 300 to 400 per cent more blood than is required by the body foradequate bodywide tissue nutrition.
Ventricular function curve for the left ventricle during the course of hemorrhagic shock.Curve A represents the control function curve; curve B, 117 min; curve C, 247 min; curve D,280 min; curve E, 295 min; and curve F, 310 min after the initial hemorrhage. (Redrawn fromCrowell JW, Guyton AC: Am J Physiol 203:248, 1962.)
Vasomotor Failure.• Diminished blood flow to the brain’s vasomotor centerdepresses the center so much that it becomes progressivelyless active and finally totally inactive.• Complete circulatory arrest to the brain for 10 to 15 minutes,depresses the vasomotor center such that no evidence ofsympathetic discharge can be demonstrated.• The resulting loss of sympathetic tone then reduces cardiacoutput and peripheral resistance which reduces mean arterialpressure and intensifies the inadequate cerebral perfusion.• Various endogenous opioids, such as enkephalins and β-endorphin, may be released into the brain substance or intothe circulation in response circulatory shock, which furtherdepresses brainstem centres.• Vasomotor center usually does not fail if the arterialpressure remains above 30 mm Hg
Acidosis.• The inadequate blood flow during shock affects the metabolismof all cells in the body.• Hypo-perfusion reduces adenosine triphosphate (ATP)availability required for maintenance of transmembranepotential. Leaky cell membranes cause interstitial fluid uptakeand massive cell oedema.• This oedema obstructs adjacent capillaries reducing oxygendelivery• The decreased oxygen delivery to the cells accelerates theproduction of lactic acid and other acid metabolites by thetissues.• Impaired kidney function prevents adequate excretion of theexcess H+, and generalized metabolic acidosis ensues .• The resulting depressant effect of acidosis on the heart furtherreduces tissue perfusion and thus aggravates the metabolicacidosis
• Acidosis also diminishes the reactivity of the heart andresistance vessels to neurally released and circulatingcatecholamines, and thereby intensifies the hypotension. Blockage of Very Small Vessels—“Sludged Blood.”• sluggish blood flow in the microvessels due to decreasearterial pressure leads to their blockage.• Acidosis and deterioration products from the ischemictissues, causes local blood agglutination, resulting in minuteblood clots, leading to small plugs in the small vessels.• an increased tendency for the blood cells to stick to oneanother makes it more difficult for blood to flow through themicrovasculature, giving rise to the term sludged blood.
Aberrations of blood clotting.• The alterations of blood clotting after hemorrhage aretypically biphasic. An initial phase of hypercoagulability isfollowed by a secondary phase of hypocoagulability andfibrinolysis.• In the initial phase, platelets and leukocytes adhere to thevascular endothelium, and intravascular clots, or thrombi,develop few minutes of the onset of severe hemorrhage.• Coagulation may be extensive throughout the small bloodvessels.• The initial phase is further enhanced by the release ofthromboxane A2 from various ischemic tissues.• Thromboxane A2 aggregates platelets. As more plateletsaggregate, more thromboxane A2 is released and moreplatelets are trapped
• Later tisuue ischaemia activates endothelial plasminogenactivator whilst hypo-perfusion inhibits plasminogenactivator inhibitor, thus promoting hyperfibrinolysis.• Acidosis inhibits the activity of coagulation factors andleads to increased degradation of fibrinogen.• systemic activation of the anticoagulant protein C pathwayalso occurs in later stage of shock. Increased Capillary Permeability.• In prolonged shock due to capillary hypoxia and lack ofother nutrients, the permeability of the capillaries graduallyincreases, and large quantities of fluid begin to transude intothe tissues.• Further deteriorates blood volume and cardiac output.
Release of Toxins by Ischemic Tissue.• shock causes tissues to release toxic substances, such ashistamine, serotonin, and tissue enzymes, that cause furtherdeterioration of the circulatory system.• Endotoxin is released from the bodies of dead gram-negative bacteria in the intestines.• Diminished blood flow to the intestines often causesenhanced formation and absorption of this toxin.• The circulating toxin causes cardiac depression and furtherdecreases cardiac output.
Depression of Reticuloendothelial system.• During the course of circulatory shock, reticuloendothelialsystem (RES) function becomes depressed.• The phagocytic activity of the RES is modulated by anopsonic protein and the opsonic activity in plasmadiminishes during shock.• When the RES is depressed, normal flora endotoxinsinvade the general circulation. Endotoxins produceprofound, generalized vasodilation, mainly by inducing theabundant synthesis of an isoform of nitric oxide synthasein the smooth muscle of blood vessels throughout thebody.• The profound vasodilation aggravates the hemodynamicchanges.
Vasopressin deficiency.• posterior pituitary hormone released in response to increasedplasma osmolality or decreased intravascular volume.• Plasma vasopressin levels subsequently decline, secondaryto depletion of the pituitary neurohypophyseal stores.• Decrease vasopressin decreased vasoconstriction andrenal absorption of fluid decreased blood volumedecreased cardiac output. Activation of ATP-sensitive potassium channels(KATP)• KATP channel opening allows an efflux of potassium ionsand results in membrane hyperpolarization and reducedcalcium ion movement into the cell.
• Under resting conditions, the KATP channels are closed.• Altered tissue metabolism or hypoxia leads to channelsactivation, causing vasodilatation.• Vasodilation decreased peripheral resistance,decreased venous return decreassed cardiac out put Activation of the inducible form of nitric oxidesynthase enzyme.• Nitric oxide is a vasodilator produced in vascularendothelium.• Production is controlled by a group of enzymes called nitricoxide synthases.• In shock, there is an increased expression of the inducibleform of nitric oxide synthase (NOS) due to circulatingcytokines• Increase NOS increase NO increase vasodilation
Generalized Cellular Deterioration.• Active transport of sodium and potassium through thecell membrane is greatly diminished sodium andchloride accumulate in the cells, and potassium is lostfrom the cells the cells begin to swell.• Mitochondrial activity in the tissues becomes severelydepressed.• Lysosomes in the cells in widespread tissue areas beginto break open, with release of hydrolases that causefurther intracellular deterioration.• Cellular deterioration further leads to multiorganfailure.• Lobular necrosis begins to occur in liver.
• Necrosis of the central portion of a liver lobule in severe circulatory• shock. (Courtesy Dr. J. W. Crowell.)
• Pulmonary failure “shock lung’’ ensues.• Initial phase: intrapulmonary blood volumeventilation-perfusion ratio.• Late phase: fibrin and leucocytes in interstitialand alveolar spaces.• Accumulation of Neutrophill in pulmonarycirculation release of proteases• permeability - surfactant, edema and hemorrhagies• Adult respiratory distress syndrome:
• In kidney blood flow GF oliguria.• Countercurrent mechanism failure isosthenuria• Ischemia of renal tissue azotemia and acutetubular necrosis• Marked ischemia acute renal failure.
Interactions of Positive and Negative FeedbackMechanisms• The gain of any specific mechanism varies with theseverity of the shock .• With only a slight loss of blood, mean arterial pressure iswithin the normal range and the gain of the baroreceptorreflexes is high.• With greater losses of blood, when mean arterial pressureis below 60 mm hg the baroreceptor reflex gain is zero ornear zero.• a general rule, with minor degrees of blood loss, the gainsof the negative feedback mechanisms are high, whereasthose of the positive feedback mechanisms are low andvice versa
Irreversible stage of shock• Any therapeutic intervention ceases to be effective.• Therapy can, on rare occasions, return the arterial pressureand the cardiac output to normal or near normal for shortperiods, but the circulatory system continues to deteriorate,and death ensues in another few minutes to few hours.
Why no going back from irreversiblestage of shock??• The high-energy phosphate reserves in the tissues of thebody, are greatly diminished in severe degrees of shock.• All the adenosine triphosphate downgrades to adenosinediphosphate, adenosine monophosphate, and, eventually,adenosine.• adenosine diffuses out of the cells into the circulatingblood and is converted into uric acid, a substance thatcannot re-enter the cells to reconstitute the adenosinephosphate system.• Adenosine depleted is difficult to replenish• The cellular depletion of these high energy compoundsleads to no going back.
Monitoring CO, securing CV line Adequate volume correction,inotropes and vasopressorsEarly management – RecoveryDelayed care – Progression toirreversible stageIdentifying and correcting the causeof shock