Shock is a systemic state of low tissue perfusion which is inadequate for normal cellular respiration

Greater than 90% of young, otherwise healthy patients with hypovolemic shock survive with appropriate management; in comparison, septic shock, or cardiogenic shock associated with extensive myocardial infarction, can have substantially worse mortality rates, even with optimal care.

1. shock DR. SHILPA SOMAN 1ST MDS DEPARTMENT OF ORAL PATHOLOGY AND MICROBIOLOGY. G.D.C. CALICUT

2. Contents INTRODUCTION CAUSES OF SHOCK PATHOGENESIS MORPHOLOGY STAGES OF SHOCK CLINICAL CONSEQUENCES TREATMENT CONCLUSION REFERENCES

3. Shock is a systemic state of low tissue perfusion which is inadequate for normal cellular respiration [BAILY AND LOVE] It is characterized by systemic hypotension due to either reduced cardiac output or to reduced effective circulating blood volume. The consequences are impaired tissue perfusion and cellular hypoxia What is shock ??

4. Causes of shock Cardiogenic shock Hypovolemic shock Septic shock From low cardiac output due to myocardial pump failure intrinsic myocardial damage (infarction) ventricular arrhythmias extrinsic compression, outflow obstruction (e.g., pulmonary embolism). R esults from low cardiac output due to the loss of blood or plasma volume, such as can occur with massive hemorrhage or fluid loss from severe burns. results from vasodilation and peripheral pooling of blood as part of a systemic immune reaction to bacterial or fungal infection

5. Other types. Traumatic shock .: R esulting from trauma is initially due to hypovolaemia , but even after haemorrhage has been controlled, these patients continue to suffer loss of plasma volume into the interstitium of injured tissue. Neurogenic shock .: Neurogenic shock results from causes of interruption of sympathetic vasomotor supply. Hypoadrenal shock .: Hypoadrenal shock occurs from unknown adrenal insufficiency in which the patient fails to respond normally to the stress of trauma, surgery or illness. Anaphylactic shock : denotes systemic vasodilation and increased vascular permeability caused by an IgE –mediated hypersensitivity reaction , results in tissue hypoperfusion and hypoxia.

6. Results from a severe left ventricular dysfunction from various causes. The resultant decreased cardiac output has its effects in the form of decreased tissue perfusion , movement of fluid from pulmonary vascular bed into Initially pulmonary interstitial space (interstitial pulmonary oedema) . Later alveolar spaces (alveolar pulmonary oedema). PATHOGENESIS OF CARDIOGENIC SHOCK

7. PATHOGENESIS OF HYPOVOLAEMIC SHOCK Hypovolemic shock occurs from inadequate circulating blood volume due to various causes. The major effects of hypovolemic shock are due to decreased cardiac output and low intracardiac pressure. The severity of clinical features depends upon degree of blood volume lost, haemorrhagic shock is divided into 4 types: < 1000 ml: Compensated 1000-1500 ml: Mild 1500-2000 ml: Moderate >2000 ml: Severe Increased heart rate (tachycardia) Low blood pressure (hypotension), Low urinary output (oliguria to anuria) Alteration in mental state (agitated to confused to lethargic clinical features

8. PATHOGENESIS OF SEPTIC SHOCK Associated with severe hemodynamic and hemostatic derangements , Mortality rate near 20% First among the causes of death in intensive care units and accounts for over 200,000 lost lives each year in the United States. Currently, septic shock is most frequently triggered by gram-positive bacterial infections, followed by gram-negative bacteria and fungi.

9. Systemic vasodilation and pooling of blood in the periphery leads to tissue hypoperfusion, even though cardiac output may be preserved or even increased[early]. widespread endothelial cell activation and injury, often leading to a hypercoagulable state that can manifest as DIC. Changes in metabolism that directly suppress cellular function Hypoperfusion and dysfunction of multiple organs— culminating in the extraordinary morbidity and mortality associated with sepsis.

10. The major factors contributing to its pathophysiology Inflammatory mediators Endothelial activation and injury Metabolic abnormalities Immune suppression Organ dysfuction

11. Inflammatory mediators; microbial cell wall constituents engage receptors on neutrophils, mononuclear inflammatory cells, and endothelial cells, leading to cellular activation. Toll-like receptors recognize microbial elements and trigger the responses that initiate sepsis. other pathways are probably also involved in the initiation of sepsis in humans (e.g., G-protein coupled receptors that detect bacterial peptides and nucleotide oligomerization domain proteins 1 and 2 [NOD1, NOD2]) Upon activation, inflammatory cells produce TNF, IL-1, IFN-γ, IL-12, IL-18 and high mobility group box 1 protein (HMGB1). Prostaglandins and platelet activating factor (PAF) are also elaborated.

12. These activates endothelial cells resulting in adhesion molecule expression, a procoagulant phenotype, and secondary waves of cytokine production . The complement cascade is also activated by microbial components, both directly and through the proteolytic activity of plasmin, resulting in the production of anaphylotoxins (C3a, C5a), chemotactic fragments (C5a), and opsonins (C3b) that contribute to the pro-inflammatory state . In addition, microbial components such as endotoxin can activate coagulation directly through factor XII and indirectly through altered endothelial function. The systemic procoagulant state induced by sepsis not only leads to thrombosis, but also augments inflammation through effects mediated by protease-activated receptors (PARs) found on inflammatory cells.

13. Endothelial cell activation and injury Endothelial cell activation by microbial constituents or inflammatory mediators produced by leukocytes has three major sequelae: (1) thrombosis (2) increased vascular permeability (3) vasodilation. The derangement in coagulation is sufficient to produce the fearsome complication of DIC in up to half of septic patients

14. Sepsis alters the expression of many factors so as to favor coagulation . Pro-inflammatory cytokines result in increased tissue factor production by endothelial cells (and monocytes as well), while at the same time reining in fibrinolysis by increasing PAI-1 expression. Procoagulant tendency is further exacerbated by decreased blood flow at the level of small vessels, producing stasis Deposition of fibrous thrombi in small blood vessels leads to hypoperfusion of tissues. Increased vascular permeability leads to exudation of fluid into the interstitium edema increase in interstitial fluid pressure decreased blood flow to tissues Along with increases in vasoactive inflammatory mediators (e.g., C3a, C5a, and PAF), cause the systemic relaxation of vascular smooth muscle, leading to hypotension and diminished tissue perfusion.

15. Metabolic abnormalities. Septic patients exhibit insulin resistance and hyperglycemia . Cytokines such as TNF and IL-1, stress-induced hormones (such as glucagon, growth hormone, and glucocorticoids), and catecholamines all drive gluconeogenesis. Hyperglycemia decreases neutrophil function—thereby suppressing bactericidal activity—and causes increased adhesion molecule expression on endothelial cells. This phase is frequently followed by adrenal insufficiency and a functional deficit of glucocorticoids.

16. Immune suppression . The hyperinflammatory state initiated by sepsis can activate counter-regulatory immunosuppressive mechanisms, which may involve both innate and adaptive immunity. Proposed mechanisms for the immune suppression include a shift from pro-inflammatory (TH1) to anti-inflammatory (TH2) cytokines , production of anti-inflammatory mediators (e.g., soluble TNF receptor, IL-1 receptor antagonist, and IL-10), lymphocyte apoptosis, the immunosuppressive effects of apoptotic cells, and the induction of cellular anergy. It is still debated whether immunosuppressive mediators are deleterious or protective in sepsis.

17. Organ dysfunction . Systemic hypotension, interstitial edema, and small vessel thrombosis all decrease the delivery of oxygen and nutrients to the tissues, which fail to properly utilize those nutrients that are delivered due to changes in cellular metabolism. High levels of cytokines and secondary mediators may diminish myocardial contractility and cardiac output, and increased vascular permeability and endothelial injury can lead to the adult respiratory distress syndrome. To cause the failure of multiple organs, particularly the kidneys, liver, lungs, and heart, culminating in death.

18. MORPHOLOGY The cellular and tissue changes induced by cardiogenic or hypovolemic shock are essentially those of hypoxic injury. Adrenal changes : cortical cell lipid depletion Kidneys : acute tubular necrosis Lungs : they are somewhat resistant to hypoxic injury. However, when shock is caused by bacterial sepsis or trauma, changes of diffuse alveolar damage may develop. In septic shock, the development of DIC leads to widespread deposition of fibrinrich microthrombi, particularly in the brain, heart, lungs, kidney, adrenal glands, and gastrointestinal tract. The consumption of platelets and coagulation factors also often leads to the appearance of petechial hemorrhages on serosal surface and the skin.

19. STAGES OF SHOCK Nonprogressive phase Progressive stage Irreversible stage Reflex compensatory mechanisms are activated and perfusion of vital organs is maintained Tissue hypoperfusion and onset of worsening circulatory and metabolic imbalances, including acidosis After the body has incurred cellular and tissue injury so severe that even if the hemodynamic defects are corrected, survival is not possible

20. COMPENSATED (NON-PROGRESSIVE, INITIAL, REVERSIBLE) SHOCK Early stage of shock, an attempt is made to maintain adequate cerebral and coronary blood supply by redistribution of blood so that the vital organs (brain and heart) are adequately perfused and oxygenated. Is achieved by activation of various neurohormonal mechanisms causing widespread vasoconstriction and by fluid conservation by the kidney. If the condition is treated, the compensatory mechanism may be able to bring about recovery and reestablish the normal circulation; this is called compensated or reversible shock

21. These compensatory mechanisms are as under: Widespread vasoconstriction Fluid conservation by kidney Stimulation of adrenal medulla

22. Widespread vasoconstriction In response to reduced blood flow (hypotension) and tissue anoxia, the neural and humoral factors (e.g. baroreceptors, chemoreceptors, catecholamines, renin, and angiotensin-II) are activated . These bring about vasoconstriction, particularly in the vessels of the skin and abdominal viscera. Widespread vasoconstriction is a protective mechanism as it causes increased peripheral resistance, increased heart rate (tachycardia) and increased blood pressure. Clinically cutaneous vasoconstriction is responsible for cool and pale skin in initial stage of shock. In septic shock, there is initial vasodilatation followed by vasoconstriction

23. Fluid conservation by the kidney In order to compensate the actual loss of blood volume in hypovolaemic shock, the following factors may assist in restoring the blood volume and improve venous return to the heart: Release of aldosterone from hypoxic kidney by activation of renin-angiotensin- aldosterone mechanism. Release of ADH due to decreased effective circulating blood volume. Reduced glomerular filtration rate (GFR) due to arteriolar constriction. Shifting of tissue fluids into the plasma due to lowered capillary hydrostatic pressure (hypotension)

24. Stimulation of adrenal medulla. Response to low cardiac output, adrenal medulla is stimulated to release excess of catecholamines (epinephrine and non-epinephrine) which increase heart rate and try to increase cardiac output.

25. PROGRESSIVE DECOMPENSATED SHOCK. This is a stage when the patient suffers from some other stress or risk factors (e.g. pre-existing cardiovascular and lung disease) besides persistence of the shock so that there is progressive deterioration. The effects of progressive decompensated shock due to tissue hypoperfusion are as under: i ) Pulmonary hypoperfusion ii) Tissue ischaemia It worsens pulmonary perfusion and increases vascular permeability resulting in tachypnoea and adult respiratory distress syndrome (ARDS). switch from aerobic to anaerobic glycolysis resulting in metabolic lactic acidosis. Lactic acidosis lowers the tissue pH which in turn makes the vasomotor response ineffective. This results in vasodilatation and peripheral pooling of blood.

26. IRREVERSIBLE DECOMPENSATED SHOCK. So severe that in spite of compensatory mechanisms and despite therapy and control of etiologic agent which caused the shock, no recovery takes place, it is called decompensated or irreversible shock. Its effects due to widespread cell injury include the following: i ) Progressive vasodilatation. ii) Increased vascular permeability iii) Myocardial depressant factor (MDF) iv) Worsening pulmonary hypoperfusion. v) Anoxic damage to heart, kidney, brain vi) Hypercoagulability of blood

27. i ) Progressive vasodilatation. Later stages of shock anoxia damages the capillary and venular wall and arteioles become unresponsive to vasoconstrictors and begin to dilate. Vasodilatation results in peripheral pooling of blood which further deteriorate the effective circulating blood volume. ii) Increased vascular permeability. Inflammatory mediators released by tissues which undergone anoxic damage leads to increased vascular permeability. This results in escape of fluid from circulation into the interstitial tissues thus deteriorating effective circulating blood volume.

28. iii) Myocardial depressant factor (MDF). Progressive fall in the blood pressure and persistently reduced blood flow to myocardium causes coronary insufficiency and myocardial ischaemia due to release of myocardial depressant factor (MDF). This results in further depression of cardiac function, reduced cardiac output and decreased blood flow. iv) Worsening pulmonary hypoperfusion. Further pulmonary hypoperfusion causes respiratory distress due to pulmonary oedema, tachypnoea and adult respiratory distress syndrome (ARDS)

29. v) Anoxic damage to heart, kidney, brain. Progressive tissue anoxia causes severe metabolic acidosis due to anaerobic glycolysis. There is release of inflammatory cytokines and other inflammatory mediators and generation of free radicals. Since highly specialised cells of myocardium, proximal tubular cells of the kidney, and neurons of the CNS are dependent solely on aerobic respiration for ATP generation, there is ischaemic cell death in these tissues vi) Hypercoagulability of blood. Tissue damage in shock activates coagulation cascade with release of clot promoting factor, thromboplastin and release of platelet aggregator, ADP, which contributes to slowing of blood-stream and vascular thrombosis. In this way, hypercoagulability of blood with consequent microthrombi impair the blood flow and cause further tissue necrosis. Clinically, at this stage the patient has features of coma, worsened heart function and progressive renal failure due to acute tubular necrosis.

30. Clinical Consequences In hypovolemic and cardiogenic shock Hypotension A weak, rapid pulse Tachypnea Cool, clammy, cyanotic skin. Septic shock The skin may initially be warm and flushed because of peripheral vasodilation. Individuals who survive the initial complications may enter a second phase dominated by renal insufficiency and marked by a progressive fall in urine output as well as severe fluid and electrolyte imbalances.

31. CLINICAL FEATURES OF SHOCK

32. RESUSCITATION Immediate resuscitation will ensure patent airway and adequate oxygenation and ventilation. Once ‘airway’ and ‘breathing’ are assessed and controlled, attention is directed to cardiovascular resuscitation. Conduct of resuscitation Resuscitation should not be delayed in order to definitively diagnose the source of the shocked state. The timing and nature of resuscitation depends on the type, severity and timing of insult. If there is initial doubt about the cause of shock, it is safer to assume the cause is hypovolaemia and begin with fluid resuscitation, and then assess the response. Operarative haemorrhage control should not be delayed and resuscitation should proceed in parallel with surgery.

33. Conversely, a patient with bowel obstruction and hypovolaemic shock must be adequately resuscitated before undergoing surgery otherwise the additional surgical injury and hypovolaemia induced during the procedure will exacerbate the inflammatory activation and increase the incidence and severity of end-organ insult. Fluid therapy In all cases of shock, hypovolaemia and inadequate preload must be addressed before other therapy. Use of inotropic and chronotropic agents to an empty heart will rapidly and permanently deplete the myocardium of oxygen stores reduces diastolic filling and therefore Coronary perfusion. Myocardium becomes progressively more ischaemic and unresponsive to resuscitative attempts.

34. First-line therapy, therefore, is intravenous access and administration of intravenous fluids. Access should be through short, wide-bore catheters that allow rapid infusion of fluids as necessary. Long, narrow lines, such as central venous catheters, have too high a resistance to allow rapid infusion and are more appropriate for monitoring than fluid replacement therapy. Type of fluids There is no ideal resuscitation fluid, and it is more important to understand how and when to administer it. In most cases of shock, there is not much difference in response to crystalloid fluids[ normal saline, Hartmann’s solution, Ringer’s lactate] and colloids [ albumin or commercially available products] On balance, there is little evidence to support the administration of colloids, which are more expensive and have worse side-effect profiles .

35. Most importantly, the oxygen carrying capacity of crystalloids and colloids is zero. If blood is being lost, the ideal replacement fluid is blood. Hypotonic solutions (dextrose etc.) are poor volume expanders and should not be used in the treatment of shock unless the deficit is free water loss ( eg. diabetes insipidus) or patients are sodium overloaded ( eg. cirrhosis). Dynamic fluid response The shock status can be determined dynamically by the cardiovascular response to the rapid administration of a fluid bolus. In total, 250–500 mL of fluid is rapidly given (over 5–10 minutes) and the cardiovascular responses in terms of heart rate, blood pressure and central venous pressure are observed. Patients can be divided into ‘ responders’, ‘ transient responders ’ and ‘ nonresponders ’.

36. Responders Have an improvement in their cardiovascular status which is sustained. These patients are not actively losing fluid but require filling to a normal volume status. Transient responders Improvement which then reverts to the previous state over the next 10–20 minutes. These patients have moderate ongoing fluid losses (either overt haemorrhage or further fluid shifts reducing intravascular volume). Non-responders Severely volume depleted and are likely to have major ongoing loss of intravascular volume, usually through persistent uncontrolled haemorrhage .

37. Vasopressor and inotropic support In hypovolemia, both vasopressor and inotropic agents are not indicated as first line therapy. Administration of these agents in the absence of adequate preload rapidly leads to decreased coronary perfusion and depletion of myocardial oxygen reserves. Vasopressor agents (phenylephrine, noradrenaline) are indicated in distributive shock states (sepsis, neurogenic shock) where there is peripheral vasodilatation, and a low systemic vascular resistance, leading to hypotension despite a high cardiac output. Where the vasodilatation is resistant to catecholamines (e.g. absolute or relative steroid deficiency) vasopressin may be used as an alternative vasopressor. cardiogenic shock, or where myocardial depression complicated a shock state (e.g. severe septic shock with low cardiac output), inotropic therapy may be required to increase cardiac output and therefore oxygen delivery. The inodilator dobutamine is the agent of choice.

38. MONITORING Minimum standard for monitoring of the patient in shock is continuous heart rate and oxygen saturation monitoring, frequent non-invasive blood pressure monitoring and hourly urine output measurements. Most patients will need more aggressive invasive monitoring, including central venous pressure and invasive blood pressure monitoring.

39. Cardiovascular Cardiovascular monitoring at a minimum should include continuous heart rate (ECG) oxygen saturation pulse waveform non-invasive blood pressure. Patients whose state of shock is not rapidly corrected with a small amount of fluid should have central venous pressure monitoring and continuous blood pressure monitoring through an arterial line.

40. Central venous pressure The normal CVP response is a rise of 2–5 cmH2 O which gradually drifts back to the original level over 10–20 minutes. Patients with no change in their CVP are empty and require further fluid resuscitation. Patients with a large, sustained rise in CVP have high preload and an element of cardiac insufficiency or volume overload. Cardiac output It is not only assessment of the cardiac output but also the systemic vascular resistance and, depending on the technique used, end diastolic volume (preload) and blood volume . Measurement of cardiac output, systemic vascular resistance and preload can help distinguish the types of shock present ( hypovolaemia , distributive, cardiogenic), especially when they coexist. The information provided guides fluid and vasopressor therapy by providing real-time monitoring of the cardiovascular response.

41. Systemic and organ perfusion The goal of treatment is to restore cellular and organ perfusion. Monitoring of organ perfusion should guide the management of shock. The best measures of organ perfusion and the best monitor of the adequacy of shock therapy remains the urine output. However, this is an hourly measure and does not give a minute-to-minute view of the shocked state. The level of consciousness is an important marker of cerebral perfusion, but brain perfusion is maintained until the very late stages of shock, and hence is a poor marker of adequacy of resuscitation. Currently, the only clinical indicators of perfusion of the gastrointestinal tract and muscular beds are the global measures of lactic acidosis (lactate and base deficit) and the mixed venous oxygen saturation.

42. MONITORS OF ORGAN PERFUSION

43. Base deficit and lactate Lactic acid is generated by cells undergoing anaerobic respiration. The degree of lactic acidosis, as measured by serum lactate level and/or the base deficit, is sensitive for both diagnosis of shock and monitoring the response to therapy. Patients with a base deficit over 6 mmol/L have a much higher morbidity and mortality than those with no metabolic acidosis. Furthermore, the duration of time in shock with an increased base deficit is important, even if all other vital signs have returned to normal. the base deficit and/or lactate should be measured routinely in these patients until they have returned to normal levels. The base deficit and/or lactate should be measured routinely in these patients until they have returned to normal levels.

44. Mixed venous oxygen saturation The per cent saturation of oxygen returning to the heart from the body is a measure of the oxygen delivery and extraction by the tissues. Accurate measurement is via analysis of blood drawn from a long central line placed in the right atrium. Normal mixed venous oxygen saturation levels are 50–70 per cent. Levels below 50 per cent indicate inadequate oxygen delivery and increased oxygen extraction by the cells. This is consistent with hypovolaemic or cardiogenic shock. High mixed venous saturations (>70 per cent) are seen in sepsis and some other forms of distributive shock. In sepsis, there is disordered utilization of oxygen at the cellular level, and arteriovenous shunting of blood at the microvascular level. Thus less oxygen is presented to the cells.

45. Patients who are septic should therefore have mixed venous oxygen saturations above 70 per cent; below this level, they are not only in septic shock but also in hypovolaemic or cardiogenic shock. Although the Sv O2 level is in the ‘normal’ range, it is low for the septic state, and inadequate oxygen is being supplied to cells that cannot utilize oxygen appropriately. This must be corrected rapidly. New methods for monitoring regional tissue perfusion and oxygenation are muscle tissue oxygen probes, near-infrared spectroscopy and sublingual capnometry.

46. End points of resuscitation Traditionally, patients have been resuscitated until they have a normal pulse, blood pressure and urine output. These parameters are monitoring organ systems whose blood flow is preserved until the late stages of shock. A patient therefore may be resuscitated to restore central perfusion to the brain, lungs and kidneys and yet continue to underperfuse the gut and muscle beds. Thus activation of inflammation and coagulation may be ongoing and lead to reperfusion injury when these organs are finally perfused, and ultimately multiple organ failure.

47. This state of normal vital signs and continued underperfusion is termed ‘occult hypoperfusion’. With current monitoring techniques, it is manifested only by a persistent lactic acidosis and low mixed venous oxygen saturation. The duration patients spend in this hypoperfused state has a dramatic effect on outcome. Patients with occult hypoperfusion for more than 12 hours have two to three times the mortality of patients with a limited duration of shock. Resuscitation algorithms directed at correcting global perfusion end points (base deficit, lactate, mixed venous oxygen saturation) rather than traditional end points have been shown to improve mortality and morbidity in high-risk surgical patients.

48. CONCLUSION The prognosis varies with the origin of shock and its duration. Greater than 90% of young, otherwise healthy patients with hypovolemic shock survive with appropriate management; in comparison, septic shock, or cardiogenic shock associated with extensive myocardial infarction, can have substantially worse mortality rates, even with optimal care.

49. REFERENCES 1] ROBBINS & COTRAN PATHOLOGIC BASIS OF DISEASE – 8TH EDITION 2] TEXTBOOK OF PATHOLOGY HARSH MOHAN 6 TH EDITION 3] BAILEY AND LOVE’S SHORT PRACTICE OF SURGERY 26TH EDITION