Farhana Zakaria

1. Farhana Zakaria

2. Contents • Definition of shock • Classification of shock • Pathogenesis of shock • Clinical features in shock • Biochemical changes in shock • Tissue changes in irreversible shock

3. Definition of Shock • Shock is an acute clinical syndrome characterised by hypoperfusion and severe dysfunction of vital organs. • There is a failure of the circulatory system to supply blood in sufficient quantities or under sufficient pressure necessary for the optimal function of organs vital to survival.

4. Classification of shock

5. Hypovolaemic Shock • Hypovolaemic shock refers to a medical or surgical condition in which rapid fluid loss results in multiple organ failure due to inadequate perfusion. • Trauma • Haemorrhage • Vomiting / diarrhoea • Burns

6. Cardiogenic Shock • Cardiogenic shock is characterized by a decreased pumping ability of the heart causing a shock-like state with inadequate perfusion to the tissues. • It occurs most commonly in association with, and as a direct result of, acute ischemic damage to the myocardium.

7. Cardiogenic Shock Intrinsic • Myocardial injury • Tachycardia • Bradycardia • Valvular defect Extrinsic • Pericardial tamponade • Tension pneumothorax • Large pulmonary embolus

8. Neurogenic Shock • Imbalance between parasympathetic and sympathetic nervous stimulation of vascular smooth muscle, resulting in sustained vasodilatation • Failure of the nervous system to control diameter of blood vessels • Causes pooling of blood and there is generally no actual blood loss • Common stimuli: head injury, spinal cord trauma, insulin reactions, anaesthesia • Classic signs of shock may not be present.

9. Septic Shock • Leading cause of death in intensive care units • Common stimuli: Gram negative bacterial infections (pseudomonas, E coli); Gram positive bacterial infections (staphylococcus and streptococcus) • Increased risk: patients with chronic illness, poor nutritional status, invasive procedure or tubes, such as Foley catheters

10. Septic Shock Systemic Inflammatory Response Syndrome (SIRS) • physiologic alternations and organ dysfunction seen with bacterial infections • 2 or more changes in these 4 factors, as follows: body temperature, heart rate, respiratory function, and peripheral leukocyte count.

11. Septic Shock Sepsis • systemic host response to infection with SIRS plus a documented infection Severe Sepsis • sepsis plus end-organ dysfunction or hypoperfusion Septic Shock • sepsis with hypotension, despite fluid resuscitation with evidence of inadequate tissue perfusion

12. Anaphylactic Shock • Result of widespread hypersensitivity (anaphylaxis) • Vasodilatation occurs leading to hypovolemia and altered cellular metabolism • Sensitized in past, re-contact with the allergen (medication, bee sting, food allergen) • Allergic reaction with large amounts of histamine released • Histamine leads to increased permeability and massive vasodilatation, • Develops respiratory distress with bronchospasm and laryngospasm

13. Pathogenesis of Shock • The human body responds to shock by activating 4 major physiologic systems: the hematologic system, the cardiovascular system, the renal system, and the neuroendocrine system.

14. Hematologic System • Activating the coagulation cascade and contracting the bleeding vessels (via local thromboxane A2 release) • Platelets are activated which form an immature clot on the bleeding source • The damaged vessel exposes collagen, which subsequently causes fibrin deposition and stabilization of the clot.

15. Cardiovascular System • Increases the heart rate, increasing myocardial contractility, and constricting peripheral blood vessels. • This response occurs secondary to an increase in release of norepinephrine and a decrease in baseline vagal tone (regulated by the baroreceptors in the carotid arch, aortic arch, left atrium, and pulmonary vessels). • The cardiovascular system also responds by redistributing blood to the brain, heart, and kidneys and away from skin, muscle, and GI tract.

16. Renal System • The kidneys respond to hemorrhagic shock by stimulating an increase in renin secretion from the juxtaglomerular apparatus. • Angiotensin II has 2 main effects, both of which help reverse hypovolaemic shock, vasoconstriction of arteriolar smooth muscle and stimulation of aldosterone secretion by the adrenal cortex.

17. Neuroendocrine System • Causes an increase in circulating antidiuretic hormone (ADH) • ADH is released from the posterior pituitary gland in response to a decrease in blood pressure (as detected by baroreceptors) and a decrease in sodium concentration. • ADH indirectly leads to an increase in reabsorption of water and salt (NaCl) by the distal tubule, the collecting ducts, and the loop of Henle.

18. STAGES OF SHOCK • Three stages1.Non-progressive, initial, compensated reversible shock2.Progressive decompensated shock3.Decompensated irreversible shock

19. Compensated reversible shock • Neurohumoral mechanisms help maintain cardiac output and blood pressure. • The net effect is tachycardia, peripheral vasoconstriction and renal conservation of fluid.

20. Compensated reversible shock • Peripheral Vasoconstriction: In response to reduced blood flow and tissue anoxia the humoral factors are activated (eg. Baroreceptors, chemoreceptors, catecholamine, renin and VEM or vasoexcitor material from hypoxic kidney) are activated.

21. Compensated reversible shock • All these bring about vasoconstriction particularly in the vessels of the skin and abdominal viscera. • It causes increased peripheral resistance, increased heart rate and increased BP. • In septic shock, there is initial vasodilatation followed by vasoconstriction.

22. Compensated reversible shock • In severe septic shock there is elevated levels of thromboxane A2 which is a potent vasoconstrictor and may augment cardiac output along with other sympathetic mechanisms.

23. Compensated reversible shock • Fluid conservation by the kidney:To compensate for the actual loss of blood volume the following factors my assist in restoring the blood volume and improve the venous return to heart1. Release of aldosterone2. Release of ADH3. Reduced GFR4. Shifting of tissue fluids

24. Compensated reversible shock • Vascular autoregulation:In response to hypoxia and acidosis, regional blood flow to the heart and brain is preserved by vasodilatation of the coronary and cerebral circulation.

25. Progressive decompensated shock • If the underlying causes are not corrected shock passes to the progressive phase, during which there is widespread tissue hypoxia. • In case of persistent O2 deficit, intracellular aerobic respiration is replaced by anaerobic glycolysis with excessive production of lactic acid.

26. Progressive decompensated shock • The resultant metabolic lactic acidosis lowers the tissue pH and blunts the vasomotor response, arteriole dilate and blood begins to pool in the microcirculation. • Peripheral pooling not only worsens the cardiac output but also puts endothelial cells at risk for developing anoxic injury with subsequent DIC. • With widespread tissue hypoxia, vital organs are affected and begin to fail. • Clinically patient becomes confused and urine output declines.

27. Decompensated (Irreversible) shock • When the shock is so severe that inspite of compensatory mechanisms and despite therapy and control of etiologic agent which caused the shock, no recovery takes place.

28. Decompensated(Irreversible) shock • Its effect due to widespread cell injury include the following:1. Progressive fall in BP due to deterioration in cardiac output attributed to release of Myocardial depressant factor (MDF)2. Severe metabolic acidosis due to anaerobic glycolysis.3. Respiratory distress due to pulmonary oedema, tachypnoea and ARDS.4. Ischaemic cell death of brain, heart and kidneys due to reduced blood supply to these organs.

29. Septic Shock • Caused by endotoxin producing gram negative bacilli, hence the term Endotoxic shock. • Major causes are E.Coli, Pseudomonas, Klebsiella. • Gram positive cocci such as Staph. aureus and Streptococcus pneumoniae

30. Septic Shock • Endotoxins are bacterial wall, Lipopolysaccharides (LPS) that are released when the cell walls are degraded. • LPS consists of a toxic fatty acid core and a complex polysaccharide coat. • Free LPS attaches to a circulating LPS binding protein and the complex binds to a cell surface receptor CD14, followed by binding of LPS to a signal transducing protein called Mammalian toll like receptor protein 4 (TLR-4)

31. Septic Shock • Engagement of TLR-4 on endothelial cells can lead directly to downregulation of natural anticoagulation mechanism including diminished synthesis of tissue factor pathway inhibitor(TFPI) and thrombomodulin. • Engagement of the receptor on monocyte and macrophages causes profound mononuclear cell activation with the subsequent production of potent effector cytokines such a interleukin1 and TNF

32. Septic Shock • At low doses, LPS serves to activate monocyte and macrophages with effects to eliminate invading bacteria and to directly activate complement. • Mononuclear phagocytes repond to LPS by producing cytokines TNF, IL1, IL6 and chemokines. • TNF and IL1 act on endothelial cell to stimulate the expression of adhesion molecule and production of other cytokine and chemokines.

33. Septic Shock • With higher levels of LPS cytokines induced secondary effectors become significant. • Systemic effects of cytokines TNF and IL1 such as fever and increased synthesis of acute phase reactants begin to occur. • LPS at higher doses results in diminished endothelial cell production of thrombomodulin and TFPI leading towards thrombosis.

34. Septic Shock • Still higher levels of LPS, syndrome of septic shock supervenes. • Same cytokines and secondary mediators now at higher levels result in1.Systemic vasodilatation (Hypotension)2.Diminished myocardial contractility3.widespread endothelial injury and activation causing systemic leucocyte adhesion in pulmonary alveolar capillary damage (ARDS)4.Activation of the coagulation system leading to DIC

35. Clinical features in shock

36. Clinical features in shock • Hypovolaemic Shock:Due to inadequate tissue perfusion 1.Skin is cold,pale,clammy,slow capillary refill2.Kidneys:Oliguria, anuria3.Brain: Drowsiness, confusion, irritability

37. Clinical features in shock • Due to increased sympathetic tone:Tachycardia, narrow pulse pressure, weak/thready pulse, sweating • Blood pressure: Hypotension • Metabolic acidosis: compensatory tachypnoea

38. Additional Clinical features • Cardiogenic Shock:Signs of Myocardial failureRaised JVPPulsus alternansGallop rhythmBasal cracklesPulmonary oedema • Obstructive shockRaised JVP, Pulsus paradoxus, Muffled heart sounds

39. Additional Clinical features • Anaphylactic shock:Signs of profound vasodilatation: Warm peripheries, low BP, tachycardiaErythema, urticaria, Angioedema, Pallor, CyanosisBronchospasm, Rhinitis,Oedema of face larynx, pharynxPulmonary oedemaHypovolaemia due to capillary leaknausea, vomitting, diarrhoea, abdominal cramps

40. Additional Clinical features • Sepsis, Severe Sepsis and septic shock:Pyrexia, rigorsHypothermiaNausea, vomittingVasodilatationWarm peripheriesBounding pulseRapid capillary refillHypotensionOccasionally signs of cutaneous vasoconstrictionJaundice, Bleeding diathesis

41. Tissue changes in irreversible shock • Morphological changes in shock are due to hypoxia resulting in degeneration and necrosis in various organs1. Brain2. Heart3. Lung4. Kidney5. Adrenals6. Intestine7. Liver8. Other organs

42. Hypoxic Encephalopathy • Cerebral ischaemia in compensated shock may produce altered state of consciousness.If BP falls below 50mmHg as occurs in systemic hypotension in prolonged shock and cardiac arrest, brain suffers from serious ischaemic damage with loss of cortical functions, coma and vegetative state.

43. Hypoxic Encephalopathy • Gross: The area supplied by the most distal branches of the cerebral arteries suffer from severe ischaemic necrosis which is usually the border zone between the anterior and middle cerebral arteries • Microscopically: changes are noticeable if ischaemia is prolonged for 12-24hrs. Neurons are more prone to develop the effects of ischaemia. Cytoplasm of the affected neurons is intensely eosinophilic and the nucleus is small pyknotic. Dead and dying nerve cells are replaced by gliosis.

44. Heart in Shock • There are two types of morphological changes in heart in all types of shock:1. Haemorrhages and necrosis: there may be small or large ischaemic areas or infarcts, particularly located in the subepicardial and subendocardial region2.Zonal lesions: These are opaque transverse contraction bands in the myocytes near the intercalated disc.

45. Shock Lung • Grossly the lungs are heavy and oedematous. • Microscopically, changes of ARDS are seen. • Briefly the changes include Congestion, Interstitial and alveolar oedema, Interstitial lymphocytic infiltrates. Alveolar hyaline membrane, Thickening and fibrosis of alveolar septa and fibrin and platelet thrombi in the pulmonary microvasculature.

46. Shock Kidney • Grossly, the kidneys are soft,swollen and congested often with a pale cortex adjacent to a hyperaemic outer medulla due to blood pooling. • Microscopically, tubular epithelial cell loss are seen at all levels of nephrons and dead epithelial casts are present in the tubular lumen and are referred to as acute tubular necrosis.

47. Adrenals in Shock • Adrenals show stress response in shock which include release of aldosterone in response to hypoxic kidney, release of glucocorticoids from adrenal cortex and catecholamines like adrenaline from adrenal medulla. • In severe shock adrenal haemorrhages may occur. • Lipid depletion of the cortex is the most frequent alteration.

48. Haemorrhagic Gastroenteropathy • The hypoperfusion of alimentary tract in conditions such as shock and cardiac failure may result in mural infarction called haemorrhagic gastroenteropathy. • Grossly: lesions are superficial ulcers, reddish purple in colour. Adjoining bowel mucosa is oedematous and haemorrhagic • Microscopically: involved areas show dilated and congested vessels and haemorrhagic necrosis of the mucosa and submucosa.

49. Liver in Shock • Due to hypoxia VDM is released from liver which causes vasodilatation. • Focal necrosis maybe seen which is centrilobular at first but can be massive. • Fatty change may occur. • Liver function may be impaired. • Other organs: Lymphnodes, Spleen and Pancreas may also show foci of necrosis

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