3.1 Sepsis

Question 1

Define sepsis

Answer 1

Life-threatening organ dysfunction due to a dysregulated host response to infection

Question 2

What is septic shock?

Answer 2

subset of sepsis -> severe abnormalities of circulation and/or cellular metabolism with persistent hypotension

results in significantly increased mortality

Question 3

What are the 2 main systems involved in sepsis?

Answer 3

Immune system

Coagulation cascade

Question 4

briefly describe the process of sepsis

Answer 4

1) microbe enters the body
2) host defence systems produces mediators to activate the immune system
3) activation of the inflammatory cascade leads to the activation of coagulation and the deposition of fibrin.

Question 5

What is the leading cause of sepsis?

Answer 5

Pneumonia

Question 6

What are the main receptors involved in sepsis?

Describe what happens upon activation and how this leads to sepsis?

Answer 6

Toll-like receptors

Upon binding to TLR:

1) Activation of signal cascade
2) Recruitment of adaptor proteins and transcription factors
3) Increased expression of cytokines -> cytokine storm (heightened response)
4) leads to acute inflammation and stimulation of adaptive immunity

inflammation -> can develop into sepsis

Question 7

List the 3 main vascular changes of inflammation

Answer 7

Vasodilation
Vascular permeability
Increased adhesion of white blood cells

Question 8

List the main cellular change that follow vascular changes during inflammation

Answer 8

Cellular recruitment and activation of Neutrophils (polymorphonuclear leukocytes)

Question 9

What are the 2 main results of inflammation and how do these affect starlings law?

What is the overall consequence?

Answer 9

1) Vasodilation ➞ decreased systemic vascular resistance (TPR)

[BP = CO x SVR] therefore, decreased CV will cause an increase in CO to maintain BP

2) Fluid leakage ➞ absolute hypovolaemia (decrease blood volume)

decrease volume is sensed by baroreceptors, as [CO=SV x HR] in order to increase CO we must increase HR which results in compensatory tachycardia

Question 10

What cause decreased perfusion to organs? Why?

Answer 10

The reduced circulating volume reduces the venous return: so CO falls, BP falls more and the flow reduces to organs.

The activated coagulation pathway is also causing microthrombi to distribute throughout circulation

Question 11

What happens to the lungs as sepsis progresses?

Answer 11

Increased respiratory rate (tachypnoea) due to insufficient O2 delivery to tissues. Seen as Rapid breathing and Shortness of breath

Surfactant dries out resulting in difficulty taking breaths. This can lead to ARDS Acute respiratory distress syndrome

Question 12

What happens in the tissues as sepsis progresses?

How does the body compensate?

Answer 12

1) Decreased oxygen causes tissues to enter hypoxic state
2) They switch to anaerobic metabolism (utilise pyruvic acid to create lactic acid in tissues)
3) lactic acid decrease pH, causes pain and leads to metabolic acidosis
4) body compensates for acidosis by increase RR (to increase O2 supply to tissues)

*note patients with sepsis already have a high RR, so this only increase is dangerously

Question 13

What happens to the kidneys as sepsis progresses?

How can kidney function be measured and indicate sepsis?

Answer 13

Decreased urine output due to decreased blood flow to kidneys

Both urine output and creatinine can be an indicator of kidney function and therefore sepsis

Question 14

What happens to the brain as sepsis progresses? Why?

Answer 14

Confusion due to lack of O2: As the body goes deeper into shock it protects the core and continually decreases supply to the brain

Increased gluconeogenesis inhibits the ability of the brain to uptake glucose

Question 15

Name 2 things you might see in the blood as a result of sepsis

Answer 15

1) Increased blood sugar; Low O2 increases insulin resistance inhibiting the ability of the peripheral tissues to upstage glucose. The body’s stress response releases cortisol which promotes gluconeogenesis.
2) CRP causes insulin resistance and is a marker of inflammation

Question 16

Why does systemic inflammation result in activation of coagulation? (3)

Answer 16

1) Tissue factor mediated thrombosis
2) Down regulation of physiological anticoagulant mechanisms
3) Inhibition of fibrinolysis

Question 17

Explain the process of coagulation in sepsis

Answer 17

1) Bacteria detected by host immune system
2) Initiates inflammatory response
3) Activation of complement cascade (C3 to C3a and C3b -> activates complement C5 ->
4) C5 increases expression of tissue factor on surface of monocytes and activates MAC)
5) Increaed tissue factor triggers coagulation cascade resulting in build up of fibrin

Question 18

What is purapura and when is it seen?
What does this indicate?
How reliable of a sign is it?

Answer 18

Systemic coagulation activation may lead to depletion of circulating coagulation factors and platelets leading to bleeding -> “disseminated intravascular coagulation”

This is seen as purapura

Do not always appear in sepsis, or can appear very late during septic shock -> do NOT rely on presence of Purapura for diagnosis

• Fibrin deposits also make it difficult for the limited blood to circulate

Question 19

What acronym helps you recognize sepsis?

Answer 19

TIME:
Temperature (higher or lower than normal)
Infection 
Mental decline 
Extremely ill; severe pain or discomfort

Question 20

Name 5 red flags of sepsis

Answer 20

1) HR >130 bpm
2) Resp rate >25 per min
3) Not passed urine in last 18 hours
4) Lactate >2mmol/L
5) Acute confusional state

Question 21

What is SIRS and what criteria define it?

Answer 21

SIRS: systemic inflammatory response syndrome

Present if there are at least 2 of the following present (No longer the primary way to identify sepsis due to low speciality and sensitivity)

1) Temp below 36 or above 38.3
2) HR >90
3) Abnormal RR and pCO2
4) Increase in WBC count
5) Confusion
6) Blood glucose >7mmol/L in non-diabetic patients

Question 22

What is the SOFA and the qSOFA score?

Answer 22

Sequential Organ Failure Assessment

SOFA: suspected infection plus a change in 2 or more of the criteria involving resp, hematology (platelet count), liver (serum bilirubin), renal (serum creatinine or urine output), brain and cardiovascular (hypotension and vasopressor requirement)

qSOFA is a quick bedside way to assess:

1) RR of 22/min +
2) altered mentation (Glasgow coma scale < 15)
3) systolic BP of 100 mmHg or less

Question 23

What does NEWS stand for and what is it used for?

Answer 23

National Early warning score -> used to identify anybody in a “quick assessment” using vital signs

Question 24

How would you manage sepsis?

(Hint: The sepsis 6 bundle) “give 3, take 3”

Answer 24

Give…

1) IV antibiotics: initially broad to ensure the microorganism will respond
2) IV fluids
3) O2

Take…

1) Lactate levels
2) Blood culture; identify the presence of infection
3) Urine output measurement

Question 25

What type of antibiotic is doxycycline and how does it work?

Answer 25

Tetracycline

Doxycycline inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit

Question 26

What does a broad-spectrum antibiotic mean?

Answer 26

Covers gram (+), (-) and anaerobes