Physiology Seminar12/01/2013

PowerPoint® Seminar Slide Presentation prepared by Dr. Anwar Hasan Siddiqui, Senior Resident, Dep't of Physiology, JNMC,AMU,ALIGARH

©Dr. Anwar Siddiqui

Progressive shock

What is Shock????

• Profound hemodyamic and metabolic disturbance characterized by failure of the circulatory system to maintain adequate perfusion of vital organs.

• Normal relationship between oxygen demand and oxygen supply is impaired.

Etiology of circulatory shock

Reduced cardiac output

Hypovolaemic shock• Reduction in circulating volume causing a reduction in

venous return and consequential reduction in cardiac output• haemorrhage• Dehydration

Obstructive shock• Mechanical obstruction to normal venous return or cardiac

output• massive pulmonary embolism• tension pneumothorax• cardiac tamponade

Cardiogenic shock• Cardiac pump failure• post-myocardial infarction• cardiomyopathy• myocarditis (including septic)• drugs, e.g. β-blockers/calcium channel blockers.

Low peripheral resistanceDistributive shock• Peripheral vasodilatation – may be associated with

inadequate increase in cardiac output• septic shock• anaphylaxis• neurogenic

Endocrine shock• Addisonian crisis• Hyper/hypothyroid crisis

Stages of shock

• Nonprogressive stage (sometimes called the compensated stage) - normal circulatory compensatory mechanisms eventually cause full recovery without help from outside therapy.

• Progressive stage - without therapy, the shock becomes steadily worse until death.

• Irreversible stage - shock has progressed to such an extent that all forms of known therapy are inadequate to save the person’s life, even though, for the moment, the person is still alive.

What makes the shock to go into compensated or decompensated state???

• Depends on the feedback mechanism elicited by the shock

• Can be negative feedback mechanism or positive feedback mechanism.

• Negative feedback predominant – compensdated stage of shock

• Termed negative because the direction of the secondary change in response to shock is opposite to the direction of the initiating change

• Positive feedback mechanisms exaggerate any primary change initiated aggravating the hypotension induced by shock and tend to initiate "vicious" cycles, which may lead to decompensated or irreversible stage.

• Whether a positive feedback mechanism will lead to a vicious cycle depends on the gain of that mechanism.

• Gain is defined as the ratio of the secondary change evoked by a given mechanism to the initiating change itself.

• A gain greater than 1 induces a vicious cycle; a gain less than 1 does not

Non progressive or compensated shock

Negative feedback mechanism responsible for non progression of shock includes: Baroreceptor reflexes –

• elicit powerful sympathetic stimulation of the circulation.• Generalized arteriolar constriction is a prominent response to the

diminished baroreceptor stimulation • The reflex increase in peripheral resistance minimizes the fall in

arterial pressure caused by the reduction of cardiac output.• Vasoconstriction most pronounced in the cutaneous, skeletal

muscle and splanchnic vascular beds, slight or absent in the cerebral and coronary circulations.

• Renal vasoconstriction resisted by autoregulatory mechanism initially but with severe shock there occurs intense renal and splanchnic vasoconctriction.

Chemoreceptor reflexes.• Reductions in arterial pressure below about 60 mm Hg do not evoke

any additional responses through the baroreceptor reflexes.• Inadequate blood flow hypoxia in chemoreceptor tissues and

activation 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 the

maximal neural activity that occurs when the baroreceptors cease to be stimulated.

• With more severe degrees of cerebral ischemia, however, the vagal centers also become activated.

Reverse stress-relaxation of the circulatory system,• causes the blood vessels to contract around the diminished blood

volume, so that the blood volume that is available more adequately fills the circulation.

Formation of endogenous vasoconstrictors.• Epinephrine from the adrenal medulla, whereas norepinephrine from

both the adrenal medulla and the peripheral sympathetic nerve endings reinforce the effects of sympathetic nervous.

• Vasopressin , a potent vasoconstrictor, is actively secreted by the posterior pituitary gland.

• The plasma concentration of vasopressin rises progressively as the arterial blood pressure diminishes. The receptors responsible for the augmented release of vasopressin are the sinoaortic baroreceptors and stretch receptors in the left atrium.

• Diminished renal perfusion during shock secretion of renin from the juxtaglomerular apparatus conversion of angiotensinogen to angiotensin I ACE converts angiontensin I to angiotensin II.

• Angiotensin II is a powerfull vasoconstrictor.

Compensatory mechanisms that return the blood volume back toward normal.• Absorption of fluid into the blood capillaries from the interstitial spaces

of the body.• conservation of water and salt by the kidney by release of aldosterone.• increased thirst and increased appetite for salt, which make the person

drink water and eat salty foods if able.

Progressive stage of shock

• Caused by a vicious circle of cardiovascular deterioration.

• Positive feedback mechanism evoked by uncorrected shock results in the vicious progression.

• Requires prompt and aggressive intervention else the shock enters the irreversible stage where death is imminent

• Different types of “positive feedback” that can lead to progression of shock. (courtesy- guyton n hall textbook of physiology 11th edition

Cardiac depression.• blood pressure coronary blood flow hypoxia and decrease

nutrition of myocardium leading to diminshed contractility and reduced cardiac output.

• The consequent reduction in cardiac output leads to a further decline in arterial pressure, a classic example of a positive feedback mechanism

• The role of cardiac failure in the progression of shock during hemorrhage is controversial.

• The reduced blood flow to the peripheral tissues leads to an accumulation of vasodilator metabolites which decreases peripheral resistance and therefore aggravates the fall in arterial pressure

• All investigators agree that the heart fails terminally, but opinions differ about the importance of cardiac failure during earlier stages of hemorrhagic hypotension.

• The heart has tremendous reserve capability that normally allows it to pump 300 to 400 per cent more blood than is required by the body for adequate 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 from Crowell JW, Guyton AC: Am J Physiol 203:248, 1962.)

Vasomotor Failure.• Diminished blood flow to the brain’s vasomotor center

depresses the center so much that it becomes progressively less active and finally totally inactive.

• Complete circulatory arrest to the brain for 10 to 15 minutes, depresses the vasomotor center such that no evidence of sympathetic discharge can be demonstrated.

• The resulting loss of sympathetic tone then reduces cardiac output and peripheral resistance which reduces mean arterial pressure and intensifies the inadequate cerebral perfusion.

• Various endogenous opioids, such as enkephalins and β-endorphin, may be released into the brain substance or into the circulation in response circulatory shock, which further depresses brainstem centres.

• Vasomotor center usually does not fail if the arterial pressure remains above 30 mm Hg

Acidosis. • The inadequate blood flow during shock affects the metabolism

of all cells in the body.• Hypo-perfusion reduces adenosine triphosphate (ATP)

availability required for maintenance of transmembrane potential. Leaky cell membranes cause interstitial fluid uptake and massive cell oedema.

• This oedema obstructs adjacent capillaries reducing oxygen delivery

• The decreased oxygen delivery to the cells accelerates the production of lactic acid and other acid metabolites by the tissues.

• Impaired kidney function prevents adequate excretion of the excess H+, and generalized metabolic acidosis ensues .

• The resulting depressant effect of acidosis on the heart further reduces tissue perfusion and thus aggravates the metabolic acidosis

• Acidosis also diminishes the reactivity of the heart and resistance vessels to neurally released and circulating catecholamines, and thereby intensifies the hypotension.

Blockage of Very Small Vessels—“Sludged Blood.”• sluggish blood flow in the microvessels due to decrease

arterial pressure leads to their blockage.• Acidosis and deterioration products from the ischemic

tissues, causes local blood agglutination, resulting in minute blood clots, leading to small plugs in the small vessels.

• an increased tendency for the blood cells to stick to one another makes it more difficult for blood to flow through the microvasculature, giving rise to the term sludged blood.

Aberrations of blood clotting. • The alterations of blood clotting after hemorrhage are

typically biphasic. An initial phase of hypercoagulability is followed by a secondary phase of hypocoagulability and fibrinolysis.

• In the initial phase, platelets and leukocytes adhere to the vascular endothelium, and intravascular clots, or thrombi, develop few minutes of the onset of severe hemorrhage.

• Coagulation may be extensive throughout the small blood vessels.

• The initial phase is further enhanced by the release of thromboxane A2 from various ischemic tissues.

• Thromboxane A2 aggregates platelets. As more platelets aggregate, more thromboxane A2 is released and more platelets are trapped

• Later tisuue ischaemia activates endothelial plasminogen activator whilst hypo-perfusion inhibits plasminogen activator inhibitor, thus promoting hyperfibrinolysis.

• Acidosis inhibits the activity of coagulation factors and leads to increased degradation of fibrinogen.

• systemic activation of the anticoagulant protein C pathway also occurs in later stage of shock.

Increased Capillary Permeability.• In prolonged shock due to capillary hypoxia and lack of

other nutrients, the permeability of the capillaries gradually increases, and large quantities of fluid begin to transude into the tissues.

• Further deteriorates blood volume and cardiac output.

Release of Toxins by Ischemic Tissue.• shock causes tissues to release toxic substances, such as

histamine, serotonin, and tissue enzymes, that cause further deterioration 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 causes enhanced formation and absorption of this toxin.

• The circulating toxin causes cardiac depression and further decreases cardiac output.

Depression of Reticuloendothelial system. • During the course of circulatory shock, reticuloendothelial

system (RES) function becomes depressed.• The phagocytic activity of the RES is modulated by an

opsonic protein and the opsonic activity in plasma diminishes during shock.

• When the RES is depressed, normal flora endotoxins invade the general circulation. Endotoxins produce profound, generalized vasodilation, mainly by inducing the abundant synthesis of an isoform of nitric oxide synthase in the smooth muscle of blood vessels throughout the body.

• The profound vasodilation aggravates the hemodynamic changes.

Vasopressin deficiency.• posterior pituitary hormone released in response to

increased plasma osmolality or decreased intravascular volume.

• Plasma vasopressin levels subsequently decline, secondary to depletion of the pituitary neurohypophyseal stores.

• Decrease vasopressin decreased vasoconstriction and renal absorption of fluid decreased blood volume

decreased cardiac output.

Activation of ATP-sensitive potassium channels (KATP)• KATP channel opening allows an efflux of potassium ions

and results in membrane hyperpolarization and reduced calcium ion movement into the cell.

• Under resting conditions, the KATP channels are closed.• Altered tissue metabolism or hypoxia leads to channels

activation, causing vasodilatation.• Vasodilation decreased peripheral resistance,

decreased venous return decreassed cardiac out put

Activation of the inducible form of nitric oxide synthase enzyme.• Nitric oxide is a vasodilator produced in vascular

endothelium.• Production is controlled by a group of enzymes called nitric

oxide synthases.• In shock, there is an increased expression of the inducible

form of nitric oxide synthase (NOS) due to circulating cytokines

• Increase NOS increase NO increase vasodilation

Generalized Cellular Deterioration.• Active transport of sodium and potassium through the

cell membrane is greatly diminished sodium and chloride accumulate in the cells, and potassium is lost from the cells the cells begin to swell.

• Mitochondrial activity in the tissues becomes severely depressed.

• Lysosomes in the cells in widespread tissue areas begin to break open, with release of hydrolases that cause further intracellular deterioration.

• Cellular deterioration further leads to multiorgan failure.

• 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 volume

ventilation-perfusion ratio.• Late phase: fibrin and leucocytes in interstitial

and alveolar spaces.• Accumulation of Neutrophill in pulmonary

circulation 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

acute tubular necrosis• Marked ischemia acute renal failure.

Interactions of Positive and Negative Feedback Mechanisms

• The gain of any specific mechanism varies with the severity of the shock .

• With only a slight loss of blood, mean arterial pressure is within the normal range and the gain of the baroreceptor reflexes is high.

• With greater losses of blood, when mean arterial pressure is below 60 mm hg the baroreceptor reflex gain is zero or near zero.

• a general rule, with minor degrees of blood loss, the gains of the negative feedback mechanisms are high, whereas those of the positive feedback mechanisms are low and vice versa

Irreversible stage of shock

• Any therapeutic intervention ceases to be effective.• Therapy can, on rare occasions, return the arterial pressure

and the cardiac output to normal or near normal for short periods, but the circulatory system continues to deteriorate, and death ensues in another few minutes to few hours.

Why no going back from irreversible stage of shock??

• The high-energy phosphate reserves in the tissues of the body, are greatly diminished in severe degrees of shock.

• All the adenosine triphosphate downgrades to adenosine diphosphate, adenosine monophosphate, and, eventually, adenosine.

• adenosine diffuses out of the cells into the circulating blood and is converted into uric acid, a substance that cannot re-enter the cells to reconstitute the adenosine phosphate system.

• Adenosine depleted is difficult to replenish• The cellular depletion of these high energy compounds

leads to no going back.

Monitoring CO, securing CV line Adequate volume correction, inotropes and vasopressors

Early management – RecoveryDelayed care – Progression to irreversible stage

Identifying and correcting the cause of shock

Thanx for patience hearing…….