Id 1Y2: Sepsis

Front 1

Systemic Inflammatory Response Syndrome (SIRS)

Definition?

Criteria?

Can be triggered by?

Back 1

A clinical response arising from a nonspecific insult, including at least 2 of the following:
- Temperature >=38C or <=36C (High or low temp)

- HR >=90 beats/min (tachycardia)

- Respirations >=20/min (tachypnea)

- WBC count >12,000/mm3 or  <4,000/mm3 or >10% immature neutrophils (segmented neutrophils or bands)

SIRS can be triggered by infection, trauma, burns, and other inflammatory conditions (main point = may/may NOT be due to infection)

Front 2

Sepsis = ______ + _______

Severe Sepsis = _______ + ________

Back 2

Sepsis = SIRS + Infection

Severe Sepsis = Sepsis + Organ Failure

Organ failure:
- Cardiovascular (refractory hypotension)
- Renal (renal insufficiency)
- Respiratory (hypoxemia)
- Hepatic (shock liver)
- Hematologic (marrow suppression)
- Central nervous system (confusion)
-Metabolic acidosis

Front 3

Septic Shock = _______ + _________

Back 3

Septic Shock = sepsis + hypotension refractory to volume repletion/resuscitation + end organ signs / perfusion abnormalities

Front 4

Multiple Organ Dysfunction Syndrome

Definition: Dysfunction of ___ or more organs

Mortality is near 100% when?

Back 4

Dysfunction of 2 or more organs

When 4 or more systems involved, 100% mortalitiy

Front 5

Why is incidence of sepsis increasing?

Name 4

Back 5

Invasive techniques allow bacteria direct access to the blood stream (venous and arterial catheters, ventilators, foley catheters, intra-aortic balloon pumps, transvenous pacemakers, ventricular assist devices, etc)

Immunocompromised patients who lack host defenses against bacteria

Debilitated patients kept alive longer with severe underlying diseases.

Antibiotic resistance.

Front 6

Causal Pathogens

Majority of sepsis cases are caused by gram ______ organisms (56%)

Greatest increase in the past 20 years has been in _______ infections

Back 6

Majority of cases of sepsis now caused by gram-POSITIVE organisms (56%)

Though still relatively uncommon, the greatest increase in the past 20 years has been in FUNGAL infections

Front 7

Gram negative sepsis

Usually a complication of existing conditions: (name 3)

Back 7

- urinary tract infection
- pneumonia
- abdominal infection

Front 8

Which gram negative organism is an exogenous pathogen that causes sepsis?

Back 8

Pseudomonas from a water source

Front 9

LPS from a gram- organism contacts _______ (extracellular receptor anchored in cell membrane), which then "snuggles up to" _______ and ________, which all together begin signal transduction (inflammatory cascade)

Back 9

CD14

TLR4 and MD2

Front 10

CD14 in septic shock

Receptor found on which cells?

Functions to?

Back 10

A glycosylphosphatidylinositol (GPI)-anchored surface protein on macrophages and neutrophils

Transfers the lipopolysaccharide to a signalling complex consisting of a transmembrane receptor element (Toll-like receptor 4, or TLR4) and an extracellular protein (MD-2), resulting in transmission of the LPS signal to the interior of the host cell (and subsequently invoking the inflammatory cascade)

Front 11

Toll-like receptors - Sepsis

Which TLR mediates gram- signal transduction?

Which TLR mediates gram+ signal transduction?

Back 11

TLR4 appears to mediate LPS-induced signaling from gram negative bacteria

TLR-2 may mediate activation by peptidoglycan and lipoteichoic acid of gram positive bacteria

Front 12

Cytokines in human sepsis

Increased levels of which 4 are seen in some patients with sepsis?

Act on?

Excessive cytokine activity may lead to ?

Back 12

IL-1, IL-6, IL-10, and TNFα

Cytokines act on the hypothalamus, vascular endothelium and smooth muscle, and other targets to produce many of the signs and symptoms of sepsis

Excessive cytokine activity may lead to collateral tissue damage

Front 13

Sepsis:
Cytokine effect on:

1) hypothalamus?
2) capillary endothelial cell?
3) vessel wall?

Back 13

1) fever, tachycardia, tachypnea

2) [Neutrophil migration, platelet adherence, DIC with clinical thrombosis and/or hemorrhage, depletion of intravascular volume] --> cellular hypoxia --> lactic acidosis --> death

3)NO synthesis --> vasodilation --> cellular hypoxia --> lactic acidosis --> death

Front 14

Gram Positive Sepsis

T/F
Clinically indistinguishable from sepsis caused by other types of organisms (gram-)

Back 14

True

Front 15

How do gram (+) bacteria cause sepsis and septic shock?

Back 15

Peptidoglycan activation of:
cytokine production; nitric oxide -> vasodilation; complement

Lipoteichoic acid activation of:
cytokines; binding and activation via TLR-2

Toxins
superantigens: activate T cells to release cytokines
exotoxins- cytotoxic enzymes and other proteins

Front 16

Superantigens

Causes _____ ______ syndrome due to ________ or _________ (name 2 common organisms)

Back 16

Immune system (T cell) hyperactivity

Cause of toxic shock syndrome due to Staphylococcus aureus or Group A streptococcus

Front 17

What is the most common cause of ARDS?

Back 17

Sepsis

Front 18

What skin reaction/presentation is associated with pseudomonas sepsis as well as other gram negative bacteria?

Back 18

Ecthyma gangrenosum

Front 19

Management of sepsis

Back 19

- Supportive Care (Volume/ management/vasopressors/ inotropes)

- Infection diagnosis and treatment (diagnostic cultures, source identification and control, antibiotics)

- Other therapies (corticosteroids, recombinant human activated protein C, glucose control)

Front 20

Human recombinant activated protein C (HRAPC)

indicated for?

mechanism?

Back 20

Indicated for sepsis presumed due to infection with at least one associated acute organ dysfunction

mechanism:
- stimulates fibrinolysis by inhibiting factors V and VIII
- reduces inflammation by inhibiting LPS and CD14 coupling

Front 21

Potential Role of Steroids in Sepsis

T/F
Relative/functional adrenal insufficiency is common in sepsis (“critical illness-related corticosteroid insufficiency” or CIRCI)

Back 21

True

Front 22

___________ should be considered in the management strategy of patients with septic shock, particularly those patients who have responded poorly to fluid resuscitation and vasopressor agents.

Back 22

Hydrocortisone

Front 23

In patients with multiple organ failure with a septic focus, ___________ resulted in a ~4-fold reduction in mortality

Back 23

intensive insulin therapy for hyperglycemia