Causes and clinical manifestations of Sepsis

1. Causes and clinical manifestations of Sepsis Dr. G. Koshy

2. An overview A matter of semantics

8. A matter of semantics - 1 SIRS � septic inflammatory response syndrome

9. A matter of semantics - 1 SIRS � septic inflammatory response syndrome A collection of signs and symptoms in response to a variety of insults ranging from trauma to infection

10. A matter of semantics - 1 SIRS � septic inflammatory response syndrome A collection of signs and symptoms in response to a variety of insults ranging from trauma to infection Temperature >38 degrees C or < 36 degrees C, Heart rate > 90/min, Respiratory rate > 20/min or PaCO2 < 4.3 kPa, WCC > 12,000 or < 4000/cu.mm

11. A matter of semantics - 2 Severe sepsis: Sepsis associated with organ dysfunction, hypotension and hypoperfusion.

12. A matter of semantics - 2 Severe sepsis: Sepsis associated with organ dysfunction, hypotension and hypoperfusion. Evidenced by lactic acidosis, acute alteration in mental state, oliguria

13. A matter of semantics - 3 Septic shock � A subset of severe sepsis with hypotension despite adequate filling. Patients receiving inotropes and patients with MODS fall in this category.

14. A matter of semantics - 3 Septic shock � A subset of severe sepsis with hypotension despite adequate filling. Patients receiving inotropes and patients with MODS fall in this category. Refractory shock � Septic shock not responding to inotropes and vasoactive agents within one hour of commencement of treatment

15. Causes of Sepsis - 1 Infection across natural interfaces between the body and micro-organisms Skin Airway, sinuses and lungs GI tract Urinary tract and kidneys

16. Causes of sepsis - 2 Infection across unnatural interfaces between the body and micro-organisms Wounds, surgical sites Prosthesis Indwelling catheters, cannulae and lines

17. Causes of sepsis - 3 Infected tissues and organs Liver and gall bladder Abscess cavities meningitis

18. Fundamental concepts - 1 Vasodilatation leading to enhanced local blood flow to allow neutrophils and monocytes to reach the site of infection.

19. Fundamental concepts - 1 Vasodilatation leading to enhanced local blood flow to allow neutrophils and monocytes to reach the site of infection. Increased capillary leakage allowing protein rich fluid, neutrophils and monocytes to reach the site of infection

20. Fundamental concepts - 1 Vasodilatation leading to enhanced local blood flow to allow neutrophils and monocytes to reach the site of infection. Increased capillary leakage allowing protein rich fluid, neutrophils and monocytes to reach the site of infection Clotting of proteins to �wall-off� the infection

21. Fundamental concepts �2 Chemical mediators Bacterial toxins Degenerative tissue products Products of the complement cascade Clotting factors Cytokines

22. Cytokines Polypeptide in nature released by lymphocytes, macrophages, endothelium

23. Cytokines Polypeptide in nature released by lymphocytes, macrophages, endothelium Normal (constitutive) function includes thermoregulation, endocrine functions, metabolic functions and immune functions

24. Cytokines Polypeptide in nature released by lymphocytes, macrophages, endothelium Normal (constitutive) function includes thermoregulation, endocrine functions, metabolic functions and immune functions IL-1 stimulates helper T cells to produce IL-2 which promotes growth and proliferation of cytotoxic T cells

25. Cytokines Polypeptide in nature released by lymphocytes, macrophages, endothelium Normal (constitutive) function includes thermoregulation, endocrine functions, metabolic functions and immune functions IL-1 stimulates helper T cells to produce IL-2 which promotes growth and proliferation of cytotoxic T cells TNF 2a Enhances phagocytosis, neutrophil adherence, activates neutrophil degranulation

26. Other chemical mediators Prostaglandins PGI 2, PGF 2a, TXA 2 Platelet activating Factor ( PAF ) Lysosomal enzymes

27. EDRF � Nitric Oxide Synthesised from l-arginine by NO synthase

28. EDRF � Nitric Oxide Synthesised from l-arginine by NO synthase Constitutive form

29. EDRF � Nitric Oxide Synthesised from l-arginine by NO synthase Constitutive form Inducible form

30. Pathophysiology - 1 Infection is severe enough to overwhelm body defences

31. Pathophysiology - 1 Infection is severe enough to overwhelm body defences Infection is widespread

32. Pathophysiology - 1 Infection is severe enough to overwhelm body defences Infection is widespread Extensive tissue damage

33. Pathophysiology - 2 Large release of cytokines with widespread actions

34. Pathophysiology - 2 Large release of cytokines with widespread actions Extensive activation of the coagulation cascade

35. Pathophysiology - 2 Large release of cytokines with widespread actions Extensive activation of the coagulation cascade Activation of protein C which modulates both coagulation cascade and the inflammatory process

36. Cardio-vascular system in sepsis Failure of vascular tone

37. Cardio-vascular system in sepsis Failure of vascular tone Vasodilatation due to local metabolites like lactic acid, H ions, K ions

38. Cardio-vascular system in sepsis Failure of vascular tone Vasodilatation due to local metabolites like lactic acid, H ions, K ions Induced NO release

39. Cardio-vascular system in sepsis Failure of vascular tone Vasodilatation due to local metabolites like lactic acid, H ions, K ions Induced NO release Loss of reactivity of smooth muscle

40. Cardiovascular system in sepsis Failure of microcirculation

41. Cardiovascular system in sepsis Failure of microcirculation AV Shunting

42. Cardiovascular system in sepsis Failure of microcirculation AV Shunting Capillary leak and intestitial oedema

43. Cardiovascular system in sepsis Failure of microcirculation AV Shunting Capillary leak and intestitial oedema Hemoconcentration, sludging, intravascular coagulation, closure of capillary

44. Cardiovascular system in sepsis Myocardial depressant factor

45. Cardiovascular system in sepsis Myocardial depressant factor Maldistribution due to stealing

46. Clinical picture Absolute and relative hypovolaemia resulting in hypotension

47. Clinical picture Absolute and relative hypovolaemia resulting in hypotension Warm peripheries in early stages, cold and shut down in late decompensated stages

48. Clinical picture Absolute and relative hypovolaemia resulting in hypotension Warm peripheries in early stages, cold and shut down in late decompensated stages Myocardial depression

49. CNS in sepsis Failure of autoregulation, hypoperfusion, impaired oxygenation, metabolic encephalopathy and effects of endotoxins

50. CNS in sepsis Failure of autoregulation, hypoperfusion, impaired oxygenation, metabolic encephalopathy and effects of endotoxins Confusion, restlessness, irritability, stupor, coma, convulsions and death

51. Respiratory system in sepsis Protein rich fluid leaking into the intestitium

52. Respiratory system in sepsis Protein rich fluid leaking into the intestitium Protein rich fluid leaking into the alveoli

53. Respiratory system in sepsis Protein rich fluid leaking into the intestitium Protein rich fluid leaking into the alveoli Hypotension

54. Clinical picture Metabolic acidosis driven tachypnoea

55. Clinical picture Metabolic acidosis driven tachypnoea Hypoxia

56. Clinical picture Metabolic acidosis driven tachypnoea Hypoxia ARDS

57. Clinical picture Metabolic acidosis driven tachypnoea Hypoxia ARDS �Lung motor theory of sepsis�

58. Renal system in sepsis Oliguria leading onto anuria

59. Renal system in sepsis Oliguria leading onto anuria Related to hypotension and hypoperfusion

60. Renal system in sepsis Oliguria leading onto anuria Related to hypotension and hypoperfusion Stress hormones

61. Renal system in sepsis Oliguria leading onto anuria Related to hypotension and hypoperfusion Stress hormones Nephrotoxins

62. Splanchnic circulation and the GI tract Hypoperfusion

63. Splanchnic circulation and the GI tract Hypoperfusion Ischaemia of the mucosa and villi

64. Splanchnic circulation and the GI tract Hypoperfusion Ischaemia of the mucosa and villi Denudation of the villi 30min. � 60 min Trans mucosal necrosis 4 hours Transmural necrosis 6 hours

65. Splanchnic circulation and the GI tract Hypoperfusion Ischaemia of the mucosa and villi Denudation of the villi 30min. � 60 min Trans mucosal necrosis 4 hours Transmural necrosis 6 hours Translocation of bacteria �gut motor theory of sepsis�

66. Splanchnic circulation and the GI tract Hypoperfusion Ischaemia of the mucosa and villi Denudation of the villi 30min. � 60 min Trans mucosal necrosis 4 hours Transmural necrosis 6 hours Translocation of bacteria �gut motor theory of sepsis� Ischaemic injury of pancreas

67. Coagulation in sepsis Pro-coagulant state

68. Coagulation in sepsis Pro-coagulant state Disseminated intravascular coagulation and consumptive coagulopathy

69. Metabolism in sepsis Glucose metabolism � hypoglycaemia and hyperglycaemia

70. Metabolism in sepsis Glucose metabolism � hypoglycaemia and hyperglycaemia Muscle proteolysis

71. Metabolism in sepsis Glucose metabolism � hypoglycaemia and hyperglycaemia Muscle proteolysis Hepatic protein synthesis

72. Metabolism in sepsis Glucose metabolism � hypoglycaemia and hyperglycaemia Muscle proteolysis Hepatic protein synthesis Tissue metabolism prodominantly anaerobic in nature, not energy efficient

73. Summary Causes of sepsis at a clinical level

74. Summary Causes of sepsis at a clinical level Microvasculature and endothelium - at a microscopic level

75. Summary Causes of sepsis at a clinical level Microvasculature and endothelium - at a microscopic level Clinical manifestations in the light of the underlying pathophysiology

76. Thank you all