Session 3

Question 1

Define sepsis.

Answer 1

A life threatening organ dysfunction due to a disregulated host response to infection.

Question 2

Define septic shock.

Answer 2

Persisting hypotension due to sepsis.

Question 3

Define bacteraemia.

Answer 3

Presence of bacteria in the blood.

Question 4

What are some common symptoms of sepsis?

Answer 4

Fever, headache, nausea, weakness, generalised muscle aches, abdominal pain, photophobia, chills, non-specifically unwell, high resp rate, low BP, unresponsive.

Question 5

How quickly should the Sepsis Six Bundle be completed?

Answer 5

Within an hour of presentation if sepsis is suspected.

Question 6

What are the features of the Sepsis Six Bundle?

Answer 6

Give oxygen if needed, take blood cultures, IVAbx, fluid challenge, measure lactate levels, measure urine output.

Should also do FBC, U&E, EDTA (for PCR), BM, LFT, CRP, ABG, coat test and microbiology samples.

Question 7

How do patients with meningitis typically present?

Answer 7

Symptoms of sepsis, widespread purpuric rash, neck stiffness.

Question 8

What is the most common bacterial cause of sepsis?

Answer 8

Neisseria meningitidis.

Question 9

What features of Neisseria meningitidis make it adapted to increase effectiveness?

Answer 9

Lipopolysaccharide endotoxins on cell surface trigger inflammation; pills enhance attachment to host cells; polysaccharide capsule around the cell promotes adherence and prevents phagocytosis.

Question 10

Describe the inflammatory cascade.

Answer 10

• Cytokines are released and initiate thrombin production, promote coagulation and inhibit fibrinolysis
• Causes microvascular thrombosis resulting in organ ischaemia, dysfunction and failure
• Causes shock and multi-organ failure

Question 11

How is a diagnosis of sepsis confirmed?

Answer 11

From blood cultures taken before antibiotic course started and PCR may be taken.
LP may be taken and the CSF may undergo microscopy, culture and PCR.

Question 12

How is sepsis treated?

Answer 12

Antimicrobials: ceftriaxone usually used as effective against N. meningitidis.
Surgery: drainage, debridement or dead space removal.
Supportive treatments to relieve symptoms, restore patient physiologically.
Monitor/ assess regularly and consider ref to ITU

Question 13

What are some complications of sepsis?

Answer 13

Irreversible hypotension, respiratory and renal failure, raised intercranial pressure leading to coning, ischaemic necrosis of the extremities.

Question 14

What are the key features of the innate immune system?

Answer 14

Begins to act very rapidly, non-specific, no memory, doesn’t change in intensity.

Question 15

What are the body’s innate barriers?

Answer 15

Physical barriers: skin, mucous membranes, bronchial cilia.
Physiological barriers: diarrhoea, vomiting, coughing, sneezing.
Chemical barriers: Low pH in stomach, vagina and on skin; antimicrobial molecules.
Biological barriers: normal body flora.

Question 16

WHo is at high risk of infection from normal flora?

Answer 16

Asplenic and hyposplenic patients, patients with damaged or prosthetic valves, patients with PMH of infective endocarditis, immunocompromised patients.

Question 17

What infections commonly result from antibiotic use?

Answer 17

Severe colitis of the intestine due to Clostridium difficile

Thrush of the vagina due to Candida albicans

Question 18

What is the role of macrophages in innate immunity?

Answer 18

Ingest and destroy microbes via phagocytosis; produce cytokines/chemokines.

Question 19

What is the role of monocytes in innate immunity?

Answer 19

Recruited to the infection site from the blood and differentiate into macrophages.

Question 20

What is the role of neutrophils in innate immunity?

Answer 20

Recruited from the blood to sites of infection by chemokines, ingest and destroy progenitor bacteria (Staph. aureus and Strep. pyogenes).

Question 21

What is the role of mast cells/basophils in innate immunity?

Answer 21

Cause inflammation early on (vasomodulation) and are important in allergic responses.

Question 22

What is the role of eosinophils in innate immunity?

Answer 22

Defence against helminths.

Question 23

What is the role of natural killer cells in innate immunity?

Answer 23

Kill all abnormal host cells; may be virally infected or malignant.

Question 24

How are pathogens recognised by the innate immune system?

Answer 24

Using PAMPs on microbes: carbohydrate, lipid, protein and nucleic acid sequences recognised by phagocytes using PRRs.
Opsoninisation causes increased attachment of phagocytes and therefore increased clearance (essential to clear encapsulated bacteria).

Question 25

By which methods do phagocytes kill microbes?

Answer 25

Oxygen-dependent pathways (oxidative burst) or oxygen-independent pathways (lysozyme, lactoferrin, transferrin, cationic proteins, proteo-/hydrolytic enzymes.

Question 26

How is the complement system activated?

Answer 26

Cell surface microbial constituents activate it in the alternative pathway; MBL binding to mannose-containing residues on proteins on microbes activates it in the MBL pathway.

Question 27

Which complement proteins recruit phagocytes?

Answer 27

C3a and C5a.

Question 28

Which complement proteins opsonise pathogens?

Answer 28

C3b and C4b.

Question 29

Which complement proteins kill pathogens using a membrane attach complex?

Answer 29

C5-C9.

Question 30

What is the role of cytokines in the liver?

Answer 30

Cause complement activation.

Question 31

What is the role of cytokines in bone marrow?

Answer 31

To mobilise neutrophils.

Question 32

What is the role of cytokines in inflammation?

Answer 32

Cause vasodilation, an increase in vascular permeability and formation of adhesion molecules.

Question 33

What is the role of cytokines in the hypothalamus?

Answer 33

Cause an increase in body temperature.

Question 34

What conditions can cause reduced phagocytosis?

Answer 34

Chronic granulomatous disease, Chediak-Higashi syndrome, reduced spleen function, decreased neutrophil numbers.