Infection Term/Sepsis

Question 1

Host

Answer 1

An entity in which microorganisms reside and/or replicate; an entity in which microbial pathogenesis occurs

Question 2

Damage

Answer 2

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.

Question 3

Yersinia pestis - infectious disease pathology?

Answer 3

co-opts normal function of macrophages - stops signal that they have been invaded (dampened immune response)

Question 4

colonization

Answer 4

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

Question 5

mutualism

Answer 5

a state of infection whereby both the host and the microorganism benefit

Question 6

commensalism

Answer 6

a state of infection that results in either no damage or clinically inapparent damage to the host, though it can elicit and immune response

Question 7

disease

Answer 7

a clinical outcome of host damage that occurs after a threshold amount of damage has occurred

Question 8

microbial infection

Answer 8

the acquisition of a microorganism by a host

Question 9

virulence

Answer 9

the relative capacity of a microorganism to cause damage in a host

Question 10

pathogen

Answer 10

• • 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)

Question 11

latency

Answer 11

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

Question 12

virulence factor

Answer 12

a microbial component that can damage a host

Question 13

examples of virulence factor?

Answer 13

toxins
enzymes (often degradative - Dnase, elastase)
enzymes - catalases, phosphatoases, dismutases
proteins that impair signaling

Question 14

opportunist

Answer 14

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)

Question 15

streptococci can cause skin infections - can also cause disease in immunocompromised pts.

Answer 15

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Question 16

two goals with pathogens?

Answer 16

eradicate it

limit tissue damage associated with inflamm

Question 17

if you have a weak immune system, give therapy that enhances the immune response/inflammation to lessen disease/host damage (increase neutrophils etc)

Answer 17

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Question 18

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!

Answer 18

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Question 19

host benefits, microbe does not?

Answer 19

fecal transplantation

Question 20

host benefits, microbe neutral?

Answer 20

intestinal flora synthesizes vitamen k and host provides niche for nutrients.

Question 21

host does not benefit, microbe does?

Answer 21

microbe causes disease

Question 22

host does not benefit, microbe is neutral?

Answer 22

infection in dead end hosts, i.e. the organism will no longer be transmitted

Question 23

pathogens that can cause disease in only strong immune responses?

Answer 23

helicobacter pylori
SARS associated cornavirus
whipples agent
theoretical agents

Question 24

pathogens that cause damage across the spectrum of immune responses but damage can be enchanted by strong immune responses

Answer 24

shigella
mycoplasma pneumoniae
mumps 
chalamydia 
trypanosoma

Question 25

pathogens that cause damage primarily at the extremes of both immune repsonses

Answer 25

aspergillus and vaccina virus

Question 26

pathogens that cause damage in the setting of appropriate immune responses and produce damage at both ends of the continuum of immune responses

Answer 26

staph aureus mycobacterium tb herpes HIV

Question 27

pathogens that cause damage either in hosts with weak immune responses or in the setting of normal

Answer 27

strep pneumoniae candida albincas arboviruses toxoplasma gondii

Question 28

pathogens that only cause damage in the setting of weak immune respnoses

Answer 28

staph epidermis | pneumocystis carinii

Question 29

exposrue refers to risk of contact with a microbe

Answer 29

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Question 30

isoniazid for Tb For tb - you have a period of latency after infection before reactivation and disease

Answer 30

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Question 31

Neisseria meningitidies - go from exposure, to colonization, to infection (no latency).

Answer 31

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Question 32

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.

Answer 32

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Question 33

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.

Answer 33

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Question 34

Candida Albicans disease route

Answer 34

exposed at birth in vaginal tract commensalism disruption of gut epithelium infection or diease

Question 35

definition of sepsis

Answer 35

systemic response to an infectious agent that could be bacterial (common), viral, or fungal

Question 36

typical responses in sepsis? (4)

Answer 36

change in temp (fever or hypothermia) tachycardia tachypnea alteration in WBC count (typically up but can be low)

Question 37

humoral responses to sepsis

Answer 37

- 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)

Question 38

metabolic response to sepsis?

Answer 38

increase ACTH | glucocorticoids

Question 39

what are the benefits of bodily changes in sepsi?

Answer 39

increased WBC - fight infection tachycardia - increase CO tachypnea - increase ventilation fever - temp inhibits microbial growth

Question 40

benefits of complement in sepsis

Answer 40

opsonizes organisms, pro inflamm

Question 41

benefits of pro inflamm cytokines in sepsis

Answer 41

helps to mobilize WBCs to sites of infection

Question 42

benefits of anti-inflamm mediates in sepsis

Answer 42

prevents excessive damage to tissues

Question 43

benefits of coagulation in sepsis

Answer 43

helps to seal off infection and prevent dissemination

Question 44

benefits of changes in metabolic response in infection

Answer 44

preserves normal glucose, mobilizes energy stores

Question 45

what is severe sepsis/septic shock?

Answer 45

sepsis +evidence of insufficient organ perfusion and oxygen delivery, leading to organ dysfunction. SHOCK DOES NOT EQUAL HYPOTENSION!

Question 46

YOU DO NOT HAVE TO BE HYPOTENSIVE TO BE IN SHOCK.

Answer 46

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Question 47

def of shock?

Answer 47

insufficient organ perfusion and oxygen delivery

Question 48

Signs of severe sepsis...

Answer 48

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

Question 49

signs of significant organ dysfunction?

Answer 49

``` 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 ```

Question 50

What are the first steps in treating severe sepsis? (w/n 3 hrs of arrival - optimally w/n 1 hr)

Answer 50

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)

Question 51

the longer you wait for tx of shock, the worse the outcome for the pt

Answer 51

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Question 52

mortality rate for sepsis

Answer 52

30 to 35% for adults | 10% for children

Question 53

pathogen associate factors in shock?

Answer 53

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)

Question 54

host response to sepsis causes what factors in shock?

Answer 54

complement, coagulation, o2 and n2 radicals, proteases if excessive or uncontrolled can lead to direct tissue/ organ injury

Question 55

gram positive causes of sepsis?

Answer 55

staph aureus | strep pneumoniae

Question 56

gram negative causes of sepsis?

Answer 56

e coli klebsiella sp. pseudomonas aeruginosa

Question 57

usual sites of organ damage upon presentation with severe sepsis?

Answer 57

lung kidney (usual) liver CNS (2nd highest)

Question 58

Lung damage from sepsis?

Answer 58

impaired gas exchange requiring exogenous o2 or ventilation

Question 59

kidney damage from sepsis?

Answer 59

impaired glomerular filtration rate as evidence by increase in creatinine

Question 60

liver damage from sepsis?

Answer 60

increase in liver enzymes - typically AST and ALT

Question 61

CNS damage from sepsis?

Answer 61

loss of consciousness delirium confusion

Question 62

Tx for sepsis?

Answer 62

``` Hemodynamic support Control infection with antibiotics Ventilation for reps failure Nutrition Dialysis if renal failure CNS support-sedation ```

Question 63

Antibiotic approach for sepsis? - overview

Answer 63

Most initial therapy is empirical | Delayed or inappropriate antibiotic therapy is associated with higher mortality

Question 64

choices of antibiotics for sepsis

Answer 64

- 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

Question 65

alternatives for gram neg

Answer 65

ciproflaxacin - good for pseudomonas | carbapenems (imipenem/meropenem) - these should be used for highly resistant gram negatives (ESBLs)

Question 66

alternatives for vanco?

Answer 66

daptomycin (if worried about MRSA) | ceftriaxone(if not worried about MRSA)

Question 67

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

Answer 67

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Question 68

post-sepsis immune paralysis

Answer 68

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)