Inflammation Part II - Sepsis

What is inflammation

attempt to eliminate injurious stimuli and promote healing

What is non-specific inflammation

different types of insults employ same response of cells and molecules

dysregulation of the immune response can lead to

shock and sepsis

How does MI and stroke mortality compare with sepsis mortality, why?

Those who suffer acute MI only ⅓ as likely to die from MI as sepsis, and in stroke population they are only ½ likely to die

Because of advancements in MI and stroke treatment (something not yet achieved for sepsis)

Sepsis _th leading cause of death in Canada in 2011

12th

What is one determining factor for sepsis

Age: very young (neonates and infants) and very old (65+) most susceptible

Most common comorbidities of sepsis (3)

HIV, cancer, diabetes

Mortality rates higher in what gender in sepsis

males

Nosocomial infections, impact on sepsis mortality rate

acquired in hospital > sepsis have higher mortality rate than cases where pt was admitted with sepsis

sepsis 3 guidelines criteria that indicate

systemic inflammatory response (SIRS)

Sepsis-3 guideline markers (4) describe each

• Higher or lower body temp, increased HR and RR, high or low WBC

  • Temp >38° C or <36° C

  • HR > 90 

  • RR > 20 (or a PaCO2 0f <32 mm Hg)

• Another marker: large proportion of  bands immature WBCs > body ramping up production as part of inflammatory response

  • WBC > 12,000 mm3 or < 4,000 mm3, or > 10% bands

can sepsis-3 diagnose sepsis?

NO (some pts display SIRS while not suffering from an infection or adverse outcomes, and vice versa)

sepsis is

life-threatening organ dysfunction from dysregulated host response to infection

Sepsis now described by organ dysfunction assessed by

2-point change in sepsis-related sequential organ failure score (SOFA)

2 main components of sepsis

1. Infection (suspected/confirmed)

2. Organ dysfunction (measured by SOFA score of 2 or more)

septic shock

subset of sepsis in which particularly profound circulatory, cellular and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone

Shock pts can be identified by (2)

• Elevated serum lactate levels (> than 2 mmol/L)

• Need for vasopressor therapy to maintain a mean arterial pressure (MAP) of 65 mm Hg (i.e.: fluid resistant hypotension)

In-hospital mortality rate for septic shock is >__% and associated with

40%

hypotension even with fluid resuscitation

Quick SOFA (qSOFA)

non-invasive bedside tool can be used to help screen clients for sepsis

When is further evaluation of sepsis warranted when using qSOFA

If a client has an infection (suspected or confirmed) and is experiencing 2 or more of the following:

1. Systolic BP ≤ 100mm Hg

2. Altered mentation

3. RR ≥ 22/min

What tool is now more commonly used for predicting sepsis diagnosis and in-hospital mortality for patients with sepsis

Early warning score (EWS)

What tool used to evaluate mental status, score of <__ indicates altered mentation, scores <__ can prompt further evaluation

Glasgow coma scale

<13 indicates altered mentation

<15 can prompt further evaluation

those who survive sepsis may develop, describe, mortality rate

persistent critical illness (PCI)

organ dysfunction continues up to months from initial presentation of sepsis or septic shock

(mortality rate 20-40%)

PCI often results in, and increases risk of (statistics)

disability (cognitive dysfunction, neuropathies, dysfunctional immune systems)

increases risk of sepsis survivor mortality (up to 75% within 5 years)

Effects of sepsis and septic shock due to dysfunction at _________ level

cellular

What is happening at cellular level in sepsis and shock, describe

Cytotoxic hypoxia cell unable to use oxygen efficiently

__________ can be elevated due to (2)

Lactate can be elevated due to increased glycolysis and inability of mitochondria to use lactate

How does mitochondrial dysfunction impact cells

reduces ATP > E deficit in cells

Mitochondrial dysfunction can then lead to (2)

organ dysfunction and greater risk for mortality

Without _____, ______ can proceed in cytoplasm of cell but products (2) cannot enter citric acid cycle in _______

oxygen, glycolysis

pyruvate and lactate cannot enter citric acid cycle in mitochondrion

Explain hypoxia-induced metabolic changes to Na/K pump

• Far fewer ATP produced by glycolysis > E deficit > affecting systems (i.e. Na/K pump)

  • Allows Na flow into cell and K leave cell > damaging gradient

  • Gradient required for action potentials (neurons, muscle cells)

Explain what happens with water in hypoxia-induced metabolic changes

• Water flows into cell > swelling > cellular membrane disruption > release of lysosomal contents

  • Initiate positive feedback loops > greater deterioration of the cell

Ongoing anaerobic metabolism causes increase in

lactate

Explain what happens with pH in hypoxia-induced metabolic changes

drops due to protons generated by hydrolysis of ATP produced by increased glycolysis

Elevations in lactate related to _______ as ________ is never produced, only lactate

acidosis, lactic acid

Explain what happens with glycogen stores in hypoxia-induced metabolic changes

depleted because of reduced nutrient delivery and increased metabolic demands

Explain what happens with protein synthesis in hypoxia-induced metabolic changes

reduced and use of intracellular plasma proteins for fuel may ensue as nutrient stores run out