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Causes and clinical manifestations of Sepsis

An overview. A matter of semantics. An overview. A matter of semanticsCauses of sepsis. An overview. A matter of semanticsCauses of sepsisFundamental concepts. An overview. A matter of semanticsCauses of sepsisFundamental conceptsPathophysiology. An overview. A matter of semanticsCauses of sepsisFundamental conceptsPathophysiologyClinical picture.

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Causes and clinical manifestations of Sepsis

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    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

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