Infection and Sepsis Student Notes PDF

Infection & Sepsis NRSG - Pathophysiology Winter 2024 Adam Elliott, MN NP Defense System The defense system works well but is not perfect, infections happen and can either inhibit or escape this system. This can lead to break down, inadequate protection, or inappropriate activation. Inadequate respo...

Infection & Sepsis NRSG - Pathophysiology Winter 2024 Adam Elliott, MN NP Defense System The defense system works well but is not perfect, infections happen and can either inhibit or escape this system. This can lead to break down, inadequate protection, or inappropriate activation. Inadequate response or immune deficiency can range from mild to life-threatening. Inappropriate responses or hypersensitivity reactions may be exaggerated (allergy), misdirected against the body’s own cells (autoimmunity), or directed against beneficial foreign tissue like transplant or transfusions (alloimmunity). These can also be mild or life-threatening. Defense System Infectious disease is not typically a major cause of death in Canada, but with recent viruses, this landscape is changing (COVID19, SARS, etc.) Infectious disease is a major cause of death in the developing world. Factors that influence the ability of a pathogen to cause disease COMMUNICABILITY INFECTIVITY VIRULENCE PATHOGENICITY PORTAL OF ENTRY TOXIGENICITY Production of toxins which can kill phagocytes Pathogens Can use many different mechanisms to resist the immune system Produce antioxidants inhibiting oxygen-dependent mechanisms Prevent functioning of antibodies Mimicry - Resembles body’s own tissue that force body to fight against itself Mutation of antigen and change surface molecules which causes a delayed immune response, causing the body not to recognize the antigen and fail. Bacterial Disease Bacteria are prokaryotes, lacking a discrete nucleus. They can be aerobic or anaerobic, mobile or immobile. Can be in different shapes and sizes (cocci, rods, spirochetes, etc.) Can be gram + or gram - Common Pathogens URTI - Haemophilus influenzae (G -) Otitis Media - Streptococcus (G+) LRTI - Pseudomonas aeruginosa (G-) GI - Clostridium Difficile (G+) Invasive GI - Helicobactor Pylori (G-) STI - Chlamydia trachomatis (Nonstainable), Neisseria gonorrhoeae (G-) Skin - Staphylococcus aureus (G+) Zoonotic - Borrelia Burgdorferi (lyme) (G-) Hosp Acq - Staphylococcus Aureus G+; escherichia coli - G FIGURE 8.1 General Structure of Bacteria. A, The structure of the bacterial cell wall determines its staining characteristics with Gram stain. A Gram-positive bacterium has a thick layer of peptidoglycan (left). A Gramnegative bacterium has a thick peptidoglycan layer and an outer membrane (right). B, Example of a Grampositive (darkly stained microorganisms, arrow) group A Streptococcus. This microorganism consists of cocci that frequently form chains. C, Example of a Gram-negative (pink microorganisms, arrow) Neisseria meningitides in cerebrospinal fluid. Neisseria form complexes of two cocci (diplococci). FIGURE 8.2 Page 179 Staphylococcus aureus Infections. Different strains of Staphylococcus aureus (Gram-positive cocci in sputum from an individual with pneumonia [centre photograph]) cause a variety of infections. The particular infection may depend on the toxin produced: exfoliative toxin (scalded skin syndrome), enterotoxins A–G (food poisoning), or toxic shock syndrome toxin-1 (TSST-1). Bacterial Chain of Infection Need an infected reservoir Infected human Animal (zoonotic) Non-living (soil, water, food, etc.) Transmission Contact: Direct, Indirect, Droplet Vehicle: Water, food, air Vector: Arthropod; Mosquito Susceptible Host Portal of Entry: Wound, m. membranes, lungs Penetrate and Evade host-cell defenses: Capsules, Exoenzymes (coagulase, kinase...) Damage Host Cells: Toxin production, exotoxins (associated with G+), endotoxins (associated with G-), siderophore secretion (deplete iron stores) Bacterial Disease Pathogens create Exotoxins and Endotoxins Exotoxins Endotoxins Enzymes that damage the plasma membranes of host cells or inactivate enzymes critical to protein synthesis. Destroy cells, cause cellular disruption. The most poisonous yet discovered is botulinum neurotoxin produced by Clostridium botulinum; less than 1 ng/kg is toxic to humans. Activate the inflammatory response and produce fever. Bacteremia occurs when bacteria are present in the blood. When these bacteria produce endotoxin (and initiate inflammatory response), it is called Sepsis or Septicemia. This creates overproduction of proinflammatory cytokines (the cells that initiate inflammatory response) Septicemia Results from failure of the body’s defense mechanisms, often by gram-negative bacteria. Endotoxins released into the blood activate complement and clotting systems, lead to capillary permeability which causes large volumes of plasma (blood) into the tissue, contributing to hypotension, and left untreated can cause cardiovascular shock, can cause DIC, and death (50% mortality) Steps to Sepsis Uncontrolled, exaggerated immune response Causes endothelium damage, cell mediator activation, disruption of coagulation system, disruption in homeostasis Vasodilation (hypOtension) due to increased capillary permiability Systemic Inflammatory Response End-organ damage leading to death if untreated Continuum of Sepsis Systemic Inflammatory Response Syndrome (SIRS) ⚬ Temp > 38 or < 36 ⚬ HR > 90 ⚬ RR > 20 or PaCO2 < 32 (resp alkalosis) ⚬ WBC > 12 or < 4 or Bands > 10% Sepsis ⚬ The systemic inflammatory response to infection. Severe Sepsis ⚬ Organ dysfunction 2ndary to Sepsis. ⚬ e.g. hypoperfusion, hypotension, acute lung injury, encephalopathy, acute kidney injury, coagulopathy. Septic Shock ⚬ Hypotension 2to Sepsis that is resistant to fluid administration & and with hypoperfusion. Sepsis SIR S T: >38 20 HR: >90 WBC: >12