Infection Term/Sepsis Flashcards
Host
An entity in which microorganisms reside and/or replicate; an entity in which microbial pathogenesis occurs
Damage
Disruption in the normal homeostatic mechanisms of a host that alter the functioning of cells, tissues, or organs. Can be caused by host and/or microbe.
- -Microorganisms produce mediators that can alter organ function or hijack cellular function.
- -The host’s cellular response can cause collateral damage. For example toxic oxygen radicals released by phagocytes to kill a microbe also may impair the function or integrity of the host cells.
Yersinia pestis - infectious disease pathology?
co-opts normal function of macrophages - stops signal that they have been invaded (dampened immune response)
colonization
a state of infection that results in a continuum of damage from none to great, with the latter leading to the induction of host responses that could eliminate or retain the microbe, or progress chronicity or disease
another def: a state of host-microoranism interaction that leads to a variable amount of host damage, from minimal to great, thereby reflecting host immune responses that have the capacity to eliminate the microorganism or to promote the development of another state
mutualism
a state of infection whereby both the host and the microorganism benefit
commensalism
a state of infection that results in either no damage or clinically inapparent damage to the host, though it can elicit and immune response
disease
a clinical outcome of host damage that occurs after a threshold amount of damage has occurred
microbial infection
the acquisition of a microorganism by a host
virulence
the relative capacity of a microorganism to cause damage in a host
pathogen
- term of 1880s
- some have argued that this term should be eliminated from the lexicon of microbiology and infectious disses
- so called non-pathogens were recognized as causing disease (ex. coagulase negative staphylococci and diphtherioids –both are skin flora that can cause major disease)
latency
a state of host-microorganism interaction in which a microorganism persists in a host and can be associated with damage that can be evident at the cellular or tissue level, but is not associated with disease
virulence factor
a microbial component that can damage a host
examples of virulence factor?
toxins
enzymes (often degradative - Dnase, elastase)
enzymes - catalases, phosphatoases, dismutases
proteins that impair signaling
opportunist
causes disease when the host is impaired - can be due to pharmacologic agents that alter immunity or a genetic defect
ex. aspergillus (in those that are neutropenic)
streptococci can cause skin infections - can also cause disease in immunocompromised pts.
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two goals with pathogens?
eradicate it
limit tissue damage associated with inflamm
if you have a weak immune system, give therapy that enhances the immune response/inflammation to lessen disease/host damage (increase neutrophils etc)
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if you have a too strong response, give therapy that reduces immune response/inflamm. Give steroids - can be dangerous though because they are so nonspecific!
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host benefits, microbe does not?
fecal transplantation
host benefits, microbe neutral?
intestinal flora synthesizes vitamen k and host provides niche for nutrients.
host does not benefit, microbe does?
microbe causes disease
host does not benefit, microbe is neutral?
infection in dead end hosts, i.e. the organism will no longer be transmitted
pathogens that can cause disease in only strong immune responses?
helicobacter pylori
SARS associated cornavirus
whipples agent
theoretical agents
pathogens that cause damage across the spectrum of immune responses but damage can be enchanted by strong immune responses
shigella mycoplasma pneumoniae mumps chalamydia trypanosoma
pathogens that cause damage primarily at the extremes of both immune repsonses
aspergillus and vaccina virus
pathogens that cause damage in the setting of appropriate immune responses and produce damage at both ends of the continuum of immune responses
staph aureus
mycobacterium tb
herpes
HIV
pathogens that cause damage either in hosts with weak immune responses or in the setting of normal
strep pneumoniae
candida albincas
arboviruses
toxoplasma gondii
pathogens that only cause damage in the setting of weak immune respnoses
staph epidermis
pneumocystis carinii
exposrue refers to risk of contact with a microbe
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isoniazid for Tb
For tb - you have a period of latency after infection before reactivation and disease
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Neisseria meningitidies - go from exposure, to colonization, to infection (no latency).
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If you give antibiotics to a patient, the may have elevated prothrombin time. This is because wiped out normal flora that produce vitamin K!!! Produce menaquinones for vit K production.
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Reduced immune system can allow for candida albicans to grow in immune compromised individuals! (chemotherapy) We are normally colonized by them in a commensalistic relationship.
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Candida Albicans disease route
exposed at birth in vaginal tract
commensalism
disruption of gut epithelium
infection or diease
definition of sepsis
systemic response to an infectious agent that could be bacterial (common), viral, or fungal
typical responses in sepsis? (4)
change in temp (fever or hypothermia)
tachycardia
tachypnea
alteration in WBC count (typically up but can be low)
humoral responses to sepsis
- complement
- coagulation cascade - Protease activated receptors (PAR) are the link between coagulate band inflammation. high levels of thrombin activate these receptors (PAR1) and this causes disruption of the endothelial cell-barrier function
- pro inflammatory mediators (IL-1)
- anti-inflamm mediatorys (IL-10)
metabolic response to sepsis?
increase ACTH
glucocorticoids
what are the benefits of bodily changes in sepsi?
increased WBC - fight infection
tachycardia - increase CO
tachypnea - increase ventilation
fever - temp inhibits microbial growth
benefits of complement in sepsis
opsonizes organisms, pro inflamm
benefits of pro inflamm cytokines in sepsis
helps to mobilize WBCs to sites of infection
benefits of anti-inflamm mediates in sepsis
prevents excessive damage to tissues
benefits of coagulation in sepsis
helps to seal off infection and prevent dissemination
benefits of changes in metabolic response in infection
preserves normal glucose, mobilizes energy stores
what is severe sepsis/septic shock?
sepsis +evidence of insufficient organ perfusion and oxygen delivery, leading to organ dysfunction.
SHOCK DOES NOT EQUAL HYPOTENSION!
YOU DO NOT HAVE TO BE HYPOTENSIVE TO BE IN SHOCK.
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def of shock?
insufficient organ perfusion and oxygen delivery
Signs of severe sepsis…
at least two of
- temp >38.3 or <36
- HR>90
- RR >20
- WBC >1200 or <4000 or >10% bands
and 1 sign of significant organ dysfunction
signs of significant organ dysfunction?
lactate >2 mmol/L INR >1.6 or aPTT>60 platelets <100,000 total bilirubin >2.0 mg/dl creatine >2.0 mg/dl urine output <0.5 mg/kg/hr systolic BP <90 or MAP <65
What are the first steps in treating severe sepsis? (w/n 3 hrs of arrival - optimally w/n 1 hr)
initial lactate measurement
2 blood cultures prior to antibiotic. culture lines too.
broad spectrum IV
fluid resuscitation with 30 mL/kg crystalloid fluids
admit to suitable level of care (usually ICU)
the longer you wait for tx of shock, the worse the outcome for the pt
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mortality rate for sepsis
30 to 35% for adults
10% for children
pathogen associate factors in shock?
overgrowth and tissue invasion causes direct tissue and organ injury
bacteria also release endotoxin/exotoin (leads to both direct tissue/organ injury but also inflamm cell recruitment)
host response to sepsis causes what factors in shock?
complement, coagulation, o2 and n2 radicals, proteases if excessive or uncontrolled can lead to direct tissue/ organ injury
gram positive causes of sepsis?
staph aureus
strep pneumoniae
gram negative causes of sepsis?
e coli
klebsiella sp.
pseudomonas aeruginosa
usual sites of organ damage upon presentation with severe sepsis?
lung
kidney (usual)
liver
CNS (2nd highest)
Lung damage from sepsis?
impaired gas exchange requiring exogenous o2 or ventilation
kidney damage from sepsis?
impaired glomerular filtration rate as evidence by increase in creatinine
liver damage from sepsis?
increase in liver enzymes - typically AST and ALT
CNS damage from sepsis?
loss of consciousness
delirium
confusion
Tx for sepsis?
Hemodynamic support Control infection with antibiotics Ventilation for reps failure Nutrition Dialysis if renal failure CNS support-sedation
Antibiotic approach for sepsis? - overview
Most initial therapy is empirical
Delayed or inappropriate antibiotic therapy is associated with higher mortality
choices of antibiotics for sepsis
- vancomycin for gram positives + a third generation cephalosporin for gram negatives
- if you think the pt has pseudomonas (neturopenic/on ventilator, etc) then cefipime of piperacillin/tazobactam
- if pseudomonas is not part of your consideration, then ceftriaxone is fine
alternatives for gram neg
ciproflaxacin - good for pseudomonas
carbapenems (imipenem/meropenem) - these should be used for highly resistant gram negatives (ESBLs)
alternatives for vanco?
daptomycin (if worried about MRSA)
ceftriaxone(if not worried about MRSA)
when appropriate, deescalate antibiotics to make them match the sensitivity of the organism. For example, do not need a carbapenem to treat penicillin sensitive pneumococcus
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post-sepsis immune paralysis
following tx, period of weeks to months where pt is vulnerable to new infection
WBC will be normal
will have defective DC’s and macrophages, buildup of trigs, and TGFbeta (antiinflamm)
