Infection, Inflammation, Sepsis, and Pneumonia

Question 1

What is infection?

Answer 1

• Invasion of tissues by pathogens

Question 2

What is inflammation?

Answer 2

• Complex protective reaction
• Body’s response to invasion
• Damaging agents destroyed, diluted
• Without inflammation, survival not possible
• Process has consequences- potentially harmful (autoimmune)
• Local or systemic (e.g. sepsis)
• Acute or chronic

Question 3

What are the cardinal signs of inflammation?

Answer 3

• Rubor, calor, dolor, tumour, loss of function
• Increased blood flow- vascular dilation- redness and heat
• Increased vascular permeability gives oedema- welling
• Certain chemical mediators stimulate nerve endings- pain (also stimulated by stretching from oedema)
• Pain and swelling can result in loss of function

Question 4

What are the components of inflammation?

Answer 4

• Vasodilation- increases blood delivery, increase temp, removes toxins
• Exudate- delivers immunoglobulins, etc, dilutes toxins, fibrinogen, increase lymphatic drainage
• Increased lymphatic drainage- bugs, phagocytes and antigens to immune system
• Cells- killers, phagocytosis removes pathogenic organisms

Question 5

What are the phases of inflammation?

Answer 5

• First, dilation of vessels
• Fluid leads to interstitial due to increased permeability of vessels
• Second, cells move into interstitium

Question 6

Describe oedema fluid

Answer 6

• Transudate has low protein content
• • Usually caused by alterations in hydrostatic/ oncotic pressure, implies a hydrostatic problem
• An exudate has a high protein content, caused by increased vascular permeability
• Implies inflammation

Question 7

What cells are involved in inflammation?

Answer 7

• Endothelium cells- adhesion molecules (neutrophils can stick, roll and migrate from endothelial cells)
• Neutrophils degranulate
• Interleukin and cytokines destroy- cellular damage
• Cells not entirely specific

Question 8

What are the effects of mediators of inflammation?

Answer 8

• Vasodilation- prostaglandins, NO
• Vascular permeability- histamine, serotonin, C3a, C5a, bradykinin
• Fever- IL1,6, TNF-α, prostaglandins
• Pain- prostaglandins, bradykinin
• Tissue damage- neutrophil and macrophage lysosomal enzymes, oxygen metabolites

Question 9

What is sepsis?

Answer 9

• Systemic response to infections
• Life-threatening
• Organ dysfunction= breakdown in regulation of inflammatory response

Question 10

What is SIRS?

Answer 10

• Systemic inflammatory response
• Rise in temp
• Pyrexia= clinical signs
• Tachycardia >90
• Tachypnoeic- >20 breaths/minute
• Leucocytosis- high white cell >12,000mm³ or < 4,000mm³ or >10% immature neutrophils
• Non-specific
• SIRS also caused by trauma, burns, pancreatitis, and other insults

Question 11

What is sepsis?

Answer 11

• SIRS with presumed or confirmed infectious process
• Severe sepsis- involves 1 acute organ failure
• Septic shock- severe sepsis with hypotension refectory to adequate volume resuscitation

Question 12

Describe the pathogenesis of sepsis?

Answer 12

• Injury- invading pathogens
• Local inflammatory cells
• ICAMS- intracellular adhesion molecules
• Neutrophils adhesion (activation of cytokines/coagulation)
• Amplification and systemic overspill
• Leads to SIRS/ Sepsis

Question 13

What is ATP bioenergetics?

Answer 13

• Cell survival
• Mitochondria
• Reduction in ATP–> bioenergetic failure, resulting in mitochondria failure (leads to cell death)
• Less oxygen
• Leads to sepsis

Question 14

What organisms may cause Sepsis?

Answer 14

• Only 60% have conformed infection
• Similar clinical picture with all
• Gram +ve/-ve
• Positive- thick peptidoglycan layer
• Negative- thin peptidoglycan layer

Question 15

What are important gram negatives?

Answer 15

• Medically relevant cocci- Neisseria sps, Moxarella
• Medically relevant bacilli/ coccobacilli
• Lungs- haemophilus, klebsiella, psuedomonas legionella
• Urine- E coli, enterobacter, proteus
• GIT- salmonella, helicobacter

Question 16

What are important gram positives?

Answer 16

• Medically relevant cocci
• Staphylococci and streptococci
• Medically relevant bacilli
• • Clostridium, Listeria

Question 17

What is the relevance of the cell wall in bacteria?

Answer 17

• Lipopolysaccharides, aka endoto- extremely provocative to immune system
• Also confers resistance to certain antibiotics

Question 18

What is the treatment of sepsis?

Answer 18

• Recognition- more likely to survive
• Drain and culture- start antibiotics
• Respiratory rate, altered mentation, systolic BP
• Every hour delay in treatment leads to 8% increase in chance of death

Question 19

What are the physiological effects of sepsis?

Answer 19

• Altered conscious level
• Tachypnoea and hypoxia
• Jaundice, increased enzymes, decreased albumin, increased PT
• Failure to absorb diarrhoea & GI bleeding
• Tachycardia, hypotension and acidosis
• Oliguria, anuria and increased creatinine
• Decreased platelets, increased PT/APTT, decreased protein C, increased D-dimer

Question 20

Describe pathogenesis

Answer 20

• SIRS/Sepsis- systemic disorder with widespread endothelial injury and activation
• Hypoxia- appears common to range of imitating events with total or relative ischaemia
• Oxygen extraction defect- mitochondrial level- often clinically silent

Question 21

What are the mediators of sepsis response?

Answer 21

• Cytokines (pro-inflammatory and anti-inflammatory)
• Complement
• Coagulation

Question 22

What are cytokines?

Answer 22

• Diverse group of soluble proteins/peptides
• Act as humeral regulators modulating cellular activity
• Produced by variety of clels
• Local/systemic effects, pro/anti-inflammatory

Question 23

What are the pro-inflammatory cytokines?

Answer 23

• TNF-α: regulates proliferation/ apoptosis pro-inflammatory, recruiting immune cells and stimulating release of other cytokines
• IL1- similar actions to TNF-α less aggressive but synergistic
• IL6- released by stimulation by TNF-α and IL1

Question 24

What are the anti-inflammatory cytokines?

Answer 24

• IL10- inhibits release of TNF and IL1 from macrophages
• TNF receptors- present in sepsis bind TNF and limit activity
• IL-1ra- competitive inhibitor IL-1, produced by activated monocytes and PMNL

Question 25

What is the function of complement?

Answer 25

- Begins with antibody binding to cell-surface and ends with cell lysis - Proteins in pathway names C1-9 - When activates- split into 2 parts (A-smaller of two) - Activation, amplification, attack

Question 26

What is the function of coagulation in sepsis response?

Answer 26

- Key feature - Activation of extrinsic pathway by tissue factor exposed on epithelial cells - Results in release of thrombin and fibrinogenesis - Inhibitory anticoagulation pathways down-regulated

Question 27

What is the pathophysiology of pneumonia?

Answer 27

- Alveoli free from fluid - Air space- full of mucus and fluid- leads to poor diffusion, hypoxia - Aetiology- most likely bacteria (75%), other organisms that cause it- viruses, fungi, mycoplasma, parasites, chemicals