Sepsis Flashcards
define sepsis
Life-threatening organ dysfunction due to a dysregulated host response to infection
what triggers sepsis
an infection
what is sepsis response
Overwhelming/excessive immune response (to infection) that causes organ dysfunction
what differentiates sepsis from an infection
presence of organ dysfunction differentiates sepsis from an infection
what causes pathology in sepsis
organ dysfunction
not pathology
mortality risk due to sepsis
1 in 5
high
what can organ dysfunction be identified as
an acute change in total SOFA score of 2 or more
septic shock
Sepsis which is underlying circulatory and cellular and/or metabolic abnormalities are marked enough to substantially increase mortality
Clinically defined as sepsis with persisting hypotension that requires vasopressors to maintain the mean arterial pressure at less than 65mmHg and with a serum lactate concentration of greater than 2mmoll-1
- Persistent hypotension despite fluid resuscitation
Immune dysfunction is severe enough to change metabolic activity and increase mortality
SOFA
organ failure score
wide range of tests done on a variety of organs in labs
qSOFA
quick SOFA
tool to clinically characterise patients at risk of sepsis (at risk of prolonged ICU or death)
- No lab tests needed
- can be used in community to assess sepsis risk
3 components measured in qSOFA
Respiratory ≥ 22 breaths/min
- elevated
Altered mentation (Glasgow Coma Scale <15)
Systolic blood pressure ≤ 100 mm Hg
- lower
3 criteria of Glasgow Coma Scale
eye opening
verbal response
best motor response
what is a disability score for Glasgow Coma Scale?
less than maximum 15
what causes sepsis
Any infection can trigger sepsis In susceptible individuals
- Meningitis, small cut, UTI, sore throat
common sites of infections in ICU
Lungs (64%)
Abdomen (20%)
Bloodstream (15%)
Urinary system(14%)
source of infections in adults in ICUs
Gram positive bacteria (47%)
- most common
- Staph aureus (20%)
Gram negative bacteria (62%)
Fungal (19%)
- Candida (17%)
Candida bloodstream infections associated with higher ICU mortality compared with bacterial infections
what type of infection are children more susceptible to
viral infections
e.g. viral meningitis
what 2 classes of factors contribute to infections progressing to sepsis
microbial and host factors
microbial factors that can contribute to sepsis
Virulence factors
- LPS
- Lipoteichoic acid
- Peptidoglycan
- Pili, fimbriae, capsule etc
Virulence contributes to pathogenicity
host factors that contribute to sepsis
Innate immunity
Adaptive immunity – protect from microbial infection
Immuno-compromised
- HIV/AIDs, cancer, autoimmunity, organ transplantation
- Taken immunosuppressant drugs
Pre-existing chronic conditions
- Diabetes, cirrhosis, CKD
Age
Genetics
what is pathogenicity determined by
interactions between microbes and host immune responses
Microbes are more pathogenic in immune-compromised hosts
- Weakened/ compromised
Give competitive advantage
- Easier to overcome host immune response
who most commonly get sepsis
elderly (disproportionate)
medically and immune-compromised patients
medical conditions which are immune compromised
Cancer Cirrhosis Autoimmunity HIV/AIDS Organ transplantation Diabetes
pathophysiology of sepsis
Dysregulated, excessive systemic inflammation
- Leads to organ dysfunction
one or more organs begin o fail
- leads to mortality
systemic effect of sepsis
Body-wide blood clotting and ‘leaky vessels’
Persistent hypotension (Septic shock – 40% in hospital mortality) - Even after fluid resuscitation Unable to keep in vessels – leak into tissues
appearance of septic shock limb
inflammed
shiny skin
red blotching due to leaky vessels
what is acute inflammation in response to localised infection
a protective immune reaction to invading microorganisms or endogenous signals from damaged cells
gives rise to cardinal signs of inflammation
- localised to site of infection
what is present in the localised site of acute inflammation
Presence of microbes or endogenous things that damage cells (PAMPS)
- pathogen associated molecular patterns
pattern recognition receptors
- Toll like receptors
DAMPS – danger associated molecular patterns
causes swelling, redness and leaky vessels localised to site of infection
what does acute inflammation result in if it is successful
clearance of the source of injury and necrotic tissues
- protective clearance at site of infection
followed by tissue repair and return to homeostasis
stages of acute inflammation in sepsis
Innate immune system recognises PAMPs (and DAMPs) through PRRs (pattern recognition receptors – toll like receptors)
- Due to damage to skin
- Microbes access underlying
Responding cells trigger inflammation through release of cytokines and chemokines.
Cytokines activate endothelial cells, vasodilation and vascular permeability.
- Immune cells can move out of blood into infected tissue to remove infection and dead tissue
Large amounts of cytokines (e.g. TNFa) activate acute phase proteins in the liver, platelet activation and symptoms of fever.
- Significant cut/very ill
- More of an endocrine function – travel in bloodstream to liver to activate coagulation system
Activation of complement
what is the function of acute inflammation
Function is to contain infection and localise it
- Stop spreading through blood stream
what happens in most inflammatory cases
the pathogen is eliminated
what type of process is the resolution of inflammation
active process
involving several regulatory mechanisms
what causes immune suppression
anti-inflammatory mediators
e.g. IL-10 and TGF-b
what happens in inflammation in sepsis
the immune response fails to eliminate the pathogen
pathogen persists
- can spread into the blood stream to other sites
what do patients with sepsis demonstrate
excessive inflammation and immune suppression
excessive inflammation causes
tissue injury
what is strongly activated in excessive inflammation
Strong activation of innate immunity via PAMPs and DAMPs
- Cytokines released in large amounts
- Start to damage host cells
- Host cells release DAMPS - activate immune system more
- Microbes persisting as well - circulate body
sustained hyperinflammation
which 3 systems are activated in sepsis
complement
coagulation
vascular
which immune systems are activated in immune suppression
both innate and adaptive immunity
what occurs in immune suppression
apoptosis of T cells and B cells
dysfunctional dendritic cells
delayed apoptosis of immune dysfunctional neutrophils
widespread impairment of adaptive immune system
- cannot fight of infection
how to treat sepsis
mostly treating the signs and symptoms
- hard to understand cause
IV antibiotics is essential to limit spread of infection
Given fluids immediately in ICU
- Colloids
- crystalloid
Vasopressors for septic shock
- Norepinephrine
- Epinephrine
- vasopressin
lung protective ventilation
urinary catheter
insulin
Time delivery and dosage is unknown
why should dentists care about sepsis
Sepsis is a rare but potentially serious complication of acute dental infections
NICE requires all health care professionals, including dental care professionals to be trained in identifying people who may have sepsis
- state, “all healthcare staff involved in assessing people’s clinical condition are given appropriate training in identifying people who may have sepsis”
what oral conditions could be potential source of sepsis
Caries
- complicated by abscess
Fungal infections
MRSA
what factors of dental abscesses make them a risk factor for sepsis
Fistula can develop – drain into the mouth or cheek lead to severe local consequence
Erode into neck or floor of mouth
- Can spread to other tissue sites
- Bacteria in pus can disseminate throughout body
when would a dental abscess develop
as a consequence of acute inflammatory response to bacterial infection
what is contained in a dental abcess
immune cells, dead tissue and LIVE bacteria
- highly infectious
how to treat a dental abscess
excision and drainage
how to treat a periapical abscess
root canal and extraction
when are antibiotics ineffective in treating abscess
ineffective (in the absence of spreading dental infection)
- No signs or symptoms of spreading infection
where can an infection in oral cavity (e.g. abscess) spread to
floor of mouth
neck (most worrying - enter blood stream)
cheek
via fistula
route determined by complicated anatomy of head and neck
red flag signs and symptoms of spreading dental infection
Temp < 36 or >38
Elevated breathing rate (> 20 breaths/min)
Elevated or reduced heart rate
Varying degrees of facial swelling
Trismus
Dehydration
- Reduced urine output can be sign of renal dysfunction
