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ECVECC Board Exam > Sepsis/SIRS > Flashcards

Sepsis/SIRS Flashcards

1
Q

Why do owners need to wear gloves when giving Chloramphenicol?

A

May cause idiosyncratic aplastic anemia

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2
Q

Which ampicillin is antipseudomonal penicillin?

A

Piperacillin-tazobactam

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3
Q

True or False: Most of the NE produced by adrenal glands are converted to epinephrine after being released to the blood stream.

A

True

About 80% NE are converted to epinephrine

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4
Q

Name a condition when “spillover” of NE can be observed.

A

Heart failure

where chronically elevated sympathetic tone cause NE “spillover” from the synaptic cleft into the bloodstream.

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5
Q

What are the two major pre-synaptic adrenoreceptors?

A

𝜶2A/D - inhibitory effect
𝜷2 - stimulatory effect

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6
Q

What are the 9 subtypes adrenoreceptors?

A

𝜶1A, 𝜶1B, 𝜶1D
𝜶2A/D, 𝜶2B, 𝜶2C
𝜷1, 𝜷2, 𝜷3

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7
Q

True or False: 𝜶1 receptors generally have stronger affinity to epinephrine than NE, while 𝜶2 receptors are the opposite.

A

False

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8
Q

True or False: 𝜷1 receptors have equal affinity to epinephrine and NE, while 𝜷2 receptors have much stronger affinity to epinephrine than NE.

A

True

𝜷2 receptors are pretty much exclusively to Epi

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9
Q

True or False: In most tissues, 𝜶1 receptor subtypes are junctional, and 𝜶2 receptor subtypes are extra-junctional.

A

True

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10
Q

Which 𝜶2 receptor subtypes locate at the pre-synaptic region and endothelium and cause vasodilation?

A

𝜶2A/D

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11
Q

Which G protein does 𝜶1, 𝜶2 and 𝜷 receptor subtypes usually couple with? are they stimulatory or inhibitory?

A

𝜶1: Gq/11 protein → activate phospholipase C → release non-mitochondrial intracellular Ca stores

𝜶2: Gi protein → inhibits adenylate cyclase → inhibit conversion of cAMP from ATP → inhibits protein kinase A → inhibit voltage-gated Ca channels

𝜷: Gs protein → activates adenylate cyclase → convert ATP to cAMP → activates protein kinase A → open voltage-gated Ca channels

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12
Q

True or False: 𝜶1A/D receptors are responsible for large arterial vasoconstriction, and 𝜶1B receptors are responsible for smaller arteries and arterioles as well as induces vascular smooth muscle growth and/or hypertrophy.

A

True

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13
Q

What is the main difference in the 𝜶 receptor subtypes distribution between artery and venous?

A

Artery: 𝜶1 receptors are junctional and 𝜶2 receptors are extra-junctional
Venous: 𝜶2 receptors are junctional and 𝜶1 receptors are extra-junctional → 𝜶2 receptors is the predominate one managing vasoconstriction

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14
Q

Which adrenoreceptors on the endothelium stimulate NO production and subsequent vasodilation?

A

𝜶2A/D

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15
Q

What is the density of 𝜶1 receptor subtypes on the myocardium compared to 𝜷?

A

𝜶1A receptor subtypes 10-15% of 𝜷 receptors
𝜶1A receptor subtypes is responsible for about 25% of inotropy

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16
Q

True or False: 𝜷1 receptors activation at the heart increase inotropy (contractility), chronotropy (HR), lusitropy (relaxation) and dromotropy (AV node conduction).

A

True

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17
Q

What is the effect of 𝜷 receptors at the vascular system?

A

Vasodilation

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18
Q

What is the effect of 𝜶 receptors and 𝜷 receptors on the coronary system?

A

𝜶 receptors - vasoconstriction
𝜷 receptors - vasodilation

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19
Q

What is the predominant 𝜷 receptor subtypes on the endothelium?

A

𝜷2 receptor

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20
Q

Stimulation of which adrenoreceptors will cause renin release? which one will cause inhibition of renin release?

A

𝜷1 → renin release
𝜶2 → inhibition of renin release

Both receptors locate at JXA

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21
Q

What is the role of 𝜷-agonist receptor kinase (𝜷-ARK).

A

When 𝜷 receptors are activated, 𝜷-ARK are activated to catalyze the 𝜷 receptors
Sustained stimulation of 𝜷 receptors → lots of 𝜷-ARK → 𝜷 receptors down regulation (both 1&2)

The remaining 𝜷 receptors will become uncoupled
Uncoupled 𝜷1: mediate myocardial apoptosis
Uncoupled 𝜷2: inhibit apoptosis

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22
Q

Rank the following effects on each receptor
Drug: Dobutamine, Epinephrine, Norepinephrine, Phenylephrine

𝜶1&2
𝜷1
𝜷2

A

𝜶1&2: Epi = NE = phenylephrine > Dobutamine (weak)
𝜷1: Epi > Dobutamine > NE (weak) > phenylephrine (none)
𝜷2: Epi > Dobutamine (weak)> Epi (none) = phenylephrine (none)

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23
Q

True or False: When 𝜶 agonist is used alone, it can decrease cardiac output.

A

True

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24
Q

How does vasopressin increase blood pressure (3 mechanisms)?

A

1) Bind to V1 receptor → increase intracellular Ca level via phosphatidylinositol-bisphosphonate cascade
2) Bind to V1 receptor → inhibit IL-𝜷 induced production of NO and cGMP, as well as iNOS mRNA expression
3) Blocks K+-sensitive ATP channels (normally activated with endotoxemia) → decreasing the amount of K+ flux and subsequently opening the voltage-dependent Ca channels → increase intracellular Ca level

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25
Q

Comparing the dopamine and norepinephrine, what dopamine is not recommended as first-line vasopressor?

A
  • Unreliable effects with different doses
  • Patients on dopamine had higher rate of tachyarrhythmias and mortality rate.
  • Dopamine also failed to normalize BP in 40% ppl with septic shock.
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26
Q

In the study published by River and colleagues on NEJM in 2001 about the Early goal-directed therapy, what was the time frame and what were the goals they set to achieve?

A

Within 6 hours

CVP ≥ 8-12 mmHg
MAP ≥ 65 mmHg
SCVO2 ≥ 70%
UOP ≥ 0.5 ml/kg/hr

  • Interventions: IV crystalloid bolus (20-30 ml/kg over 30 minutes), vasopressor, dobutamine, RBC transfusion, mechanical ventilation PRN
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27
Q

In the clinical trails associated with EGDT, what were the conclusions for ProCESS, ARISE and ProMISe studies?

  • Three nails in the coffin of EGDT
A

ProCESS
- NEJM 2014
- 1351 patients
- Three groups: EGDT, Protocol-based standard therapy by dedicated team, usual care group (no dedicated team)
- Primary outcome: 60-day mortality → NO difference
- Secondary outcome: 90-day & 1-year mortality → NO difference

ARISE
- NEJM 2014
- 1600 patients
- Two groups: EGDT vs Control
- Primary outcome: 90-day mortality → no difference
- Secondary outcome: higher vasopressor requirement in EGDT group

ProMISE
- NEJM 2015
- 1260 patients
- Two groups: EGDT vs Control
- Primary outcome:
- Secondary outcome: 90-day mortality → no difference

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28
Q

What is the definition of sepsis in 2016 Sepsis-3?

A

Life-threatening organ dysfunction caused by
dysregulated host response to infection.

NO MORE severe sepsis

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29
Q

According to the 2016 Sepsis-3, how is the organ dysfunction determined?

A

Acute change in total SOFA score ≥ 2 points

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30
Q

Write down the SOFA scoring system.

A

Cardiovascular - MAP & vasopressor
Respiratory - PaO2/FiO2
Neurological - MGCS
Renal - creatinine
Hepatic - bilirubin
Hematologic - platelet
0-4 for each category, the higher the worse

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31
Q

What are the components of qSOFA?

A

Altered mental status (GCS ≤ 15)
SAP ( ≤ 100mmHg)
Respiratory rate (≥ 22 brpm)

Score of ≥ 2 out of 3 suggests a greater risk or poorer outcome

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32
Q

In 2016 Sepsis-3, what is the definition septic shock?

A

A subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality.

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33
Q

What are the 4 clinical criteria for septic shock in 2016 Sepsis-3?

A

1) Sepsis
2) Adequate volume resuscitation
3) Vasopressor dependent hypotension (need it to maintain MAP ≥ 65 mmHg)
4) Lactate > 2 mmol/L

a clinical construct of sepsis with persisting hypotension requiring vasopressors to maintain MAP ≥65 mm Hg and having a serum lactate level >2 mmol/L (18 mg/dL) despite adequate volume resuscitation.

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34
Q

According to the 2018 The Surviving Sepsis Campaign Bundle, What are the 5 tasks that need to be accomplished with 1 hour?

A

1) Measure the Lactate. If lactate > 2 mmol/L, reassess
2) Obtain blood sample for blood culture
3) Administration broad-spectrum antibiotic
4) IV crystalloid 30 ml/kg as fluid resuscitation for hypotension or if lactate > 4 mmol/L
5) Start vasopressor is patient is still hypotensive after fluid resuscitation to maintain MAP ≥ 65 mmHg

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35
Q

According to 2021 Surviving Sepsis Campaign guidelines for sepsis & septic shock management, if a patient is shocky and sepsis is possible, what is the timing to administer antibiotic?

A

Within an hour of recognization

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36
Q

According to 2021 Surviving Sepsis Campaign guidelines for sepsis & septic shock management, what is their recommendation for using qSOFA as a single tool to screen for sepsis, septic shock?

A

Against

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37
Q

According to 2016 Surviving Sepsis Campaign guidelines for sepsis & septic shock management, what is the recommended fluid resuscitation plan for hypotensive patient?

A

30 ml/kg crystalloid within 3 hours of recognization

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38
Q

True or False: According to 2021 Surviving Sepsis Campaign guidelines for sepsis & septic shock management, it is recommended to use procalcitonin plus clinical evaluation to decide when to start antibiotics.

A

False

Against the use of procalcitonin to decide the starting time, but can be used to decide when to d/c antibiotic when optimal duration is unknown

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39
Q

According to 2016 Surviving Sepsis Campaign guidelines for sepsis & septic shock management, what is the recommendation for 𝜷-lactam administration in septic or septic shock patients?

A

Prolonged infusion

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40
Q

According to 2021 Surviving Sepsis Campaign guidelines for sepsis & septic shock management, what is their recommendation for restrictive vs liberal fluid strategies in the first 24 hours of resuscitation?

A

No conclusion - insufficient evidence

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41
Q

According to 2021 Surviving Sepsis Campaign guidelines for sepsis & septic shock management, what is their recommendation for recruitment maneuver?

A

It is recommended to use the traditional one, but the incremental PEEP/titration strategy is NOT recommended

  • “traditional” recruitment maneuver consists of the application of sustained continuous positive airway pressure (e.g., 30–40 cm H2O for 30–40 s),
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42
Q

According to 2021 Surviving Sepsis Campaign guidelines for sepsis & septic shock management, what is their recommendation for restrictive vs liberal transfusion strategies?

A

Restrictive transfusion strategy is recommended

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43
Q

According to 2021 Surviving Sepsis Campaign guidelines for sepsis & septic shock management, what is their recommendation for pharmacologic venous thromboembolism prophylaxis?

A

Recommended

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44
Q

According to 2021 Surviving Sepsis Campaign guidelines for sepsis & septic shock management, what is the threshold to start insulin therapy?

A

When BG ≥ 180 mg/dL

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45
Q

According to 2021 Surviving Sepsis Campaign guidelines for sepsis & septic shock management, what is the indication for sodium bicarbonate administration?

A

Severe metabolic acidosis (pH ≤ 7.2) and AKI

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46
Q

What are the two structures that mammalian cells have but bacterial cell walls do not?

A

Cholesterol
Phospholipid

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47
Q

What are the two major classes of antimicrobial peptides (AMPs)?

A

Defensins
Cathelicidins

  • AMPs comprise 3 main groups:
  • digestive enzymes and peptides that disrupt the microbial cell membrane
  • peptides that bind essential elements
  • peptides that act as decoys for microbial attachment
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48
Q

List 5 PAMPs and 5 DAMPs.

A

PAMPs
- Gram (+): lipotechoic acids, flagellin, peptidoglycan, mannose-rich sugar
- Gram (-): LPS, porin in the outer membrane, peptidoglycan, mannose-rich sugar, flagellin
- Acid-fast bacteria (e.g. Mycobacterium spp): mycolic acid, arabinogalactan, peptidoglycan fragments
- Bacterial and viral genomes (RNA, DNA)
- Fungal chitin
- Parasite: glycophosphatidylinositol (GPI)
- polysaccharides
- lipoprotein

DAMPs
- High mobility group box 1 protein (HMGB-1)
- DNA, RNA
- Histone
- ATP/ADP
- S 100 protein
- Heat shock protein
- Interleukin-1𝜶
- Heparan sulfate
- Hyaluronic acid
- Fibrinogen, Fibronectin
- surfactant A
- Ferritin
- Uric acid crystals
- Amyloid peptide

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49
Q

What are three major families of pattern recognizing receptors (PRRs)?

A

TLRs
NLRs
RLRs

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50
Q

NLRs

A

cytosolic PRRs that detect intracellular PAMPS and DAMPS and use the final pathways of MAPK and IKB to produce cytokines.
The other pathway they can use is the one activating INFLAMMASOMES –> caspase, IL1𝛽 and IL-18

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51
Q

List 6 cells/places you can find TLRs.

A

Dendritic cells
Endothelial cells
Macrophages
Lymphocyte B cells
Natural killer cells
Epithelial cells
Fibroblasts

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52
Q

What are the two most important TLRs?

A

TLR 2 & 4

Because they can recognize diverse PAMPs

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53
Q

What is the one structures from both Gram (+) and Gram (-) that NOD1 and NOD2 can recognize?

A

Peptidoglycans

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54
Q

True or False: Inflammasomes activate Caspase-1, and lead to the synthesis of IL-1𝜷 and IL-18.

A

True

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55
Q

What are the two cells that TNF-𝜶 predominately produced by?

A

Activated macrophage
T-cells

Pro-TNF is expressed on the cell membrane, and the cleaved by TNF-converting enzyme (TACE/ADAM17) → yield soluble and membrane-bound forms

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56
Q

What are the two main transcription factors that are activated by PRRs and subsequently activate transcriptions of various inflammatory mediators?

A

AP-1
NF-ĸB

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57
Q

What are the functions of TNF receptor 1 and 2, respectively?

A

TNFR-1: mediate the proinflammatory and apoptotic pathways associated with inflammation
TNFR-2: promotion of tissue repair and angiogenesis

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58
Q

List 4 functions of TNF-𝜶 on the endothelium which leads to the clinical signs of sepsis.

A

1) Increase production of iNOS and COX-2 → vasodilation
2) Increase expression of endothelial adhesion molecules (e.g. E-selectin, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1)) → facilitate leukocyte transmigration
3) Induce expression of procoagulant proteins (e.g. TF)
4) Down-regulate anticoagulant proteins(e.g. thrombomodulin)

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59
Q

Name 4 pro-inflammatory interleukins that NF-ĸB activates.

A

IL-1, IL-6, IL-8, IL-12

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60
Q

Anti-inflammatory response in sepsis

A

CARS

  • solube cytokine receptors
  • IL-10 and TGF𝛽
    *HSP
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61
Q

Which interleukins can induce the production of IL-1 receptor antagonist protein (IRAP-1) and soluble TNFR?

A

IL-10 (anti-inflammatory)

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62
Q

List 8 characteristics of acute phase response.

A

Fever
Neutrophilia
Activation of coagulation cascade
Activation of complement cascade
Serum iron and zinc binding
Enhance gluconeogenesis
Increase muscle catabolism
Altered lipid metabolism

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63
Q

Name 4 negative acute phase proteins.

A

Albumin
Protein C
Protein S
Antithrombin
Adiponectin
Insulin-like growth factor-1
Transferrin
Apolipoprotein A
Retinol-binding protein
Cortisol-binding protein
Transthyretin

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64
Q

True or False: serum CRP concentrations provide a sensitive but nonspecific means of measuring inflammation.

A

True

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65
Q

What are the key steps in the disregulation of the coagulation cascade in sepsis?

A
  • Tissue factor expression
  • activation of contact pathway (via kallikrein system)
  • impaired production of ADAMS13 (increased large vWf multimers)
  • impaired fibrinoysis (increased PAI synthesis)
  • dysfunction of endogenous anticoagulant (i.e. downregulation/degradation of protein C)
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66
Q

How do macrophages recognize apoptosis cell?

A

cell surface appearance of phosphatidylserine (PS)

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67
Q

List 4 positive acute phase proteins in dogs and cats.

A

C-Reactive protein
Pro-calcitonin
GSCF (granulocyte stimulating colony factor)
Haptoglobin
Serum amyloid A
𝜶1 acid glycoprotein

Dog: CRP
Cat: SAA

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68
Q

Where is procalcitonin normally produced? What about during sepsis?

A

Normal: thyroid gland C cells
Sepsis: mononuclear leukocytes

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69
Q

True or False: High-mobility group box 1 (HMGB1) is proinflammatory, can induce TF and inhibit protein C.

A

True

Produced from necrotic cells as DAMP but also actively secreted by cells stimulated by TNF𝛼
binds to TLR-2 and TLR-4 to amplify inglammatory response and recently investigated as biomarker in sepsis

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70
Q

During sepsis, how will the blood flow to the liver change?

A

Normal: portal vein 75% hepatic artery 25%
Sepsis: portal vein flow increase, hepatic artery flow decrease

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71
Q

List 3 mechanisms of liver dysfunction during sepsis.

A

1) Hypoxic injury (decrease flow from hepatic artery)
2) Glutamine deficiency → unhealthy GI tract → GI bacterial translocation to liver
3) GI tract-derived catecholamines arrive liver via portal vein → Kupffer celladrenoceptor activation → enhances production of TNF-α, IL-6, and NO

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72
Q

True or False: Sepsis-induced AKI is due to renal hypoperfusion.

A

False

It can also due to increased vasodilation (loss of gradient) or direct nephrotoxicity from the pro-inflammatory cytokines

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73
Q

What is the function of epithelial growth factor angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2)?

A

Ang-1: enhances endothelial cell survival & promotes barrier integrity
Ang-2: promotes endothelial activation and dysfunction

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74
Q

Where is angiopoietin normally stored?

A

Weibel-Palade Bodies!

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75
Q

What are the three most important fever-producing cytokines?

A

IL-1
IL-6
TNF-𝜶

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76
Q

True or False: Exogenous pyrogen is the main pyrogens that cause fever.

A

False

Exogenous pyrogens do not cause fever. They induce endogenous pyrogens and endogenous pyrogens affect the thermoregulatory center.

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77
Q

For every 1 F increase in body temperature above normal range, how much percentage of calories and water intake increases?

A

7%

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78
Q

True or False: NSAID is used to treat true fever by blocking the endogenous pyrogens.

A

False

NSAIDs inhibit the chemical mediators of fever production and allow normal thermoregulation.
They DO NOT block endogenous pyrogens

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79
Q

What are the two prostaglandins that are responsible for fever?

A

PGE2
PGF2𝜶

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80
Q

What is the definition of nosocomial infection?

A

Infection develops at least 48 hours after hospital admission without proven prior incubation.

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81
Q

List 3 risk factors of developing nosocomial infection.

A

1) Prolonged hospitalization
2) Mechanical ventilation
3) Indwelling devices

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82
Q

True or False: Zoonoses diseases are more likely to be transmitted via indirect contact than direct contact.

A

True

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83
Q

How is G-CSF induced in the bone marrow?

A

Tissue macrophage release IL-23 → specific lymphocyte release IL-17 → G-CSF stimulated from the bone marrow stromal cells

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84
Q

What is the distribution of neutrophils in the circulating pool and marginated pool in dogs and cats, respectively?

A

Circulating pool: marginated pool
Dog: 1:1
Cat: 1:3

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85
Q

What is the definition of neutropenia in dogs and cats, respectively?

A

Dog: < 2900/uL
Cat: < 2000/uL

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86
Q

What type of cell does Ehrlichia canis infect?

A

Monocytes

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87
Q

List 5 drugs that can cause neutropenia.

A

1) Estrogen
2) Chemo drug (e.g. vincristine)
3) Methimazole
4) Phenobarbital
5) Azathioprine

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88
Q

What is PIRO stand for?

A

Predisposition
Insult/infection
Response
Organ dysfunction

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89
Q

The introduction of PIRO concept shifted the sepsis paradigm from ____ to ____

A

systemic inflammatory response
ORGAN FAILURE

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90
Q

List 5 anti-inflammatory cytokines.

A

IL-4
IL-10
IL-13
Transforming growth factor β
Glucocorticoid

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91
Q

What are the common site of Gram (-) bacterial infection? What about Gram (+)?

A

Gram (-): GI, urogenital
Gram (+): skin, injured soft tissue, IV site

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92
Q

What is the definition of cryptic shock?

A

Discrepancy between macrocirculation (systemic heomdynamics) and microcirculation

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93
Q

True or False: Normally, ScvO2 is slightly lower than SvO2, but during shock state, ScvO2 can be much higher than SvO2.

A

True

Due to redistribution of the blood flow and subsequent increased oxygen extraction ratio from the splanchnic circulation.

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94
Q

Does ScvO2 include myocardial perfusion?

A

No

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95
Q

What are Mycoplasma spp.?

A

Fastidious bacteria without cell wall

Non-hemotrophic vs Hemotrophic

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96
Q

True or False: Mycoplasmas are pathogenic bacteria and normally do not exist in dogs and cats.

A

False

They are normal flora in the upper respiratory tract of dogs and cats, and in the urogenital mucosa in dogs.

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97
Q

Why 𝜷-lactam is not effective in treating Mycoplasma?

A

No cell wall!

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98
Q

What is Actinomyces spp.? What about Nocardia spp.?Which one is normal flora in animals?

A

Actinomyces spp.: Gram (+), anaerobic/microaerobic bacteria
Nocardia spp.: Gram (+), aerobic bacteria

Actinomyces spp. is normal flora in animals

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99
Q

What is the characteristic cytological findings of Actinomyces and Nocardia infection?

A

suppurative to pyogranulomatous inflammation

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100
Q

What is the main structural component of gram (+) bacteria?

A

Peptidoglycan

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101
Q

Which group of Streptococcus causes the most Streptococcal infection in dogs and cats?

A

Group G (e.g. Streptococcus canis)

  • It is also a normal microflora in dogs and cats
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102
Q

True or False: 𝜷 hemolytic streptococcal canis can cause hemolysis in dogs.

A

False

The definition of hemolytic or non-hemolytic is based on in vitro blood culture

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103
Q

What is the most common bacteria causing Streptococcal toxic shock syndrome and necrotizing fascitis/soft tissue infection in dogs and cats?

A

Group G 𝜷-hemolytic streptococcal canis

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104
Q

Describe the pathophysiology of STSS.

A

The infection typically begins with the bacteria entering the body through a wound, skin infection, or other portals of entry.

Streptococcus canis produces exotoxins, including superantigens, which play a crucial role in the development of TSS. These toxins can trigger an exaggerated immune response.

Superantigens bypass the usual immune processing and directly bind to MHC class II molecules on antigen-presenting cells and T-cell receptors, leading to massive, non-specific activation of T-cells.

The activation of a large number of T-cells results in the release of a massive amount of cytokines, including TNF-alpha, IL-1, and IL-
This “cytokine storm” leads to systemic inflammation, capillary leak, vasodilation, and ultimately, severe hypotension and shock.

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105
Q

Types of necrotizing soft tissue infactions (NSTIs)

A
  1. Type I: polymicrobial (most common in humans with >4 bacteria isolated)
  2. Type II: gram + monomicrobial (most common in dogs - Streptococcus canis)
  3. Type III: gram - monomicrobial (maritime organisms)
  4. Type IV: fungal infection (i.e. Candida)
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106
Q

What is an important consideration in the antimicrobial therapy of NSTIs?

A

stationary phase
when Strepto in high concentration stops replicating –> beta lactams not effective, so clynda much better choice

STSS
Do not use fluoroquinolones!!

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107
Q

Key intervention in STIs?

A

Surgical debridement ideally within 6h from diagnosis

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108
Q

What is the suggested criteria to diagnose STSS in dogs and cats?

A

1. Isolation of Streptococcus canis
A. From a normally sterile site
B. From a nonsterile site
2. Clinical signs of severity
A. Hypotension: SAP < 90 mmHg in dogs & < 80 mmHg in cats
B. Two or more of the following signs:
*Renal impairment: creatinine above the upper limit of the reference range
*Coagulopathy: thrombocytopenia or DIC (prolonged clo ing times, low serum fibrinogen concentration, and increased fibrin degradation products)
*Liver involvement: serum AST, ALT, or total bilirubin concentrations at least twice the upper limit of the reference range
*Acute respiratory distress syndrome defined as acute onset of diffuse pulmonary infiltrates and hypoxemia in the absence of cardiac failure, or evidence of diffuse capillary leak manifested as acute onset of pulmonary edema, or pleural or peritoneal effusions with hypoalbuminemia
*A generalized erythematous macular rash that may desquamate
*Soft tissue necrosis, including necrotizing fasciitis or myositis, or gangrene

109
Q

Why enrofloxacin administration in dogs with streptococcal infection is associated with STSS/NFM?

A

Fluoroquinolones can, in rare cases, trigger STSS by causing rapid bacterial lysis and the subsequent release of large amounts of streptococcal toxins. This can lead to an overwhelming immune response, characteristic of STSS.

110
Q

What type of bacteria is streptococcus spp.?

A

Gram (+), facultative anaerobic cocci arranged in chains

111
Q

What type of bacteria is enterococcus spp.?

A

Gram (+), facultative anaerobic cocci

112
Q

True or False: Many enterococci are intrinsically resistant to numerous antibiotics.

A

True

113
Q

What is the standard of care for serious enterococcal infections ICU patients?

A

Gentamicin (but not amikacin) + cell wall–active agent (generally ampicillin)

  • it is not appropriate to prescribe amoxicillin-clavulanate or ampicillin-sulbactam for an enterococcal isolate that is reported to be susceptible to ampicillin → they are easy to develop resistance by exposed to β-lactamase–inhibitor drugs
114
Q

What gene mediates the methicillin resistance of S. pseudintermedius? What does it change?

A

mecA gene
It encodes the production of modified penicillin binding protein (PBP) → low affinity to 𝜷-lactam

115
Q

How to determine whether a S. pseudintermedius is MRSP? Which antibiotic is used to test?

A

based on in vitro resistance to oxacillin

116
Q

True or False: If staphylococci are resistant to oxacillin, they are inherently resistant to all other β-lactams, including cephalosporins and amoxicillin-clavulanate

A

True

117
Q

What is clavulanic acid?

A

an inhibitor of β-lactamases

118
Q

True or False: All pathogenic enterococci are inferred to be intrinsically resistant to clindamycin and potentiated sulfonamides.

A

True

119
Q

True or False: Enterobacter cloacae strains are inherently resistant to amoxicillin, amoxicillin- clavulanate, narrow-spectrum cephalosporins, and cefoxitin.

A

True

120
Q

What bacteria can produce urease and alkalize the urine?

A

Proteus

It can alkalinize urine by hydrolyzing urea to ammonia

121
Q

List 6 bacteria that belongs to Enterobacteriaceae.

A

Escherichia coli
Salmonella
Enterobacter
Proteus
Klebsiella
Serratia

122
Q

What type of bacteria is Pseudomonas aeruginosa?

A

Gram (-), obligated aerobic bacteria

123
Q

List 3 drugs that are anti-pseudomonal β-lactam.

A

Ceftazidime (3rd generation cephalosporin)
Meropenem (carbapenem)
Imipenem (carbapenem)
Piperacillin
Ticarcillin

  • Other class: aminoglycoside
124
Q

Name three extended- spectrum β-lactamases (ESBL) producing bacteria.

A

E coli
Proteus mirabilis
Klebsiella pneumoniae

125
Q

On the bacterial culture and susceptibility test, what findings should you raise concern for extended- spectrum β-lactamases producing bacteria?

A

Bacteria that shows resistance to aztreonam, cefpodoxime (3rd generation), or ceftazidime

126
Q

What is extended- spectrum β-lactamases (ESBL)?

A

ESBLs are β-lactamases capable of conferring bacterial resistance to the penicillins; first-, second-, and third- generation cephalosporins; and aztreonam by hydrolysis of these antibiotics

127
Q

What color will Gram (+) and (-) be with Direct Gram staining?

A

Gram (+): purple, violet blue
Gram (-): pink, red

128
Q

In the third generation cephalosporins, which antibiotic is the only one that is effective for anaerobic infection?

A

Cefotaxime

129
Q

Are meropenem and imipenem effective to anaerobic infection?

A

Yes

130
Q

What is enrofloxacin partially metabolized to?

A

ciprofloxacin

131
Q

Which anti-fungal medication can be excreted in urine, itraconazole or fluconazole?

A

Fluconazole

132
Q

What is the main side effect of Amphotericin B?

A

Nephrotoxicity

133
Q

Which anti-fungal medication can penetrate CNS and eyes, itraconazole or fluconazole?

A

Fluconazole

134
Q

Define 90-60 rule.

A

For an antibiotic, infections due to susceptible bacteria will respond to the therapy about 90% of the time; whereas infections due to resistant bacteria will respond about 60% of the time

135
Q

What are three types of bacterial resistance?

A

1) Intrinsic
- Pseudomonas aeruginosa, which shows resistance to the majority of β-lactam antimicrobials
- all gram (-) organisms are resistant to vancomycin
2) Circumstantial
- drug cannot penetrate to the sites (e.g. CNS, eyes, prostate)
- pH makes the drug ineffective
3) Acquired

136
Q

How many CFU needs to be reached before spontaneous mutations cause resistance to two drugs?

A

> 10^14

137
Q

Name two class of drugs that are concentration-dependent.

A

Fluoroquinolone
Aminoglycoside

138
Q

For concentration-dependent antibiotic, what is the target Cmax:MIC and AUC:MIC

A

Cmax:MIC > 10-12
AUC:MIC > 100-125

  • AUC = area under the curve for 24 hours, which is influenced by both dose and interval
139
Q

For patients who receives aminoglycoside, it is recommended to monitor the serum drug levels. What are the two time points to check and what are they for?

A

1-2 hr post-administration → peak concentration (check efficacy)
4-6 hr post-administration →trough concentration (check safety)

140
Q

According to ACVIM Consensus about antibiotics, what are the three approaches to reduce antimicrobial resistance?

A

1) Prevent disease occurrence
2) Reducing overall antimicrobial drug use
3) Improved antimicrobial drug use

141
Q

In a study published by Sigal et al in 2017 JAVMA about sepsis in cats, what are the abnormal findings on blood work?

A

Metarubricytosis
Hypertriglyceridemia
High circulating muscle enzyme activities
Prolonged aPTT
Elevated D-dimer
Decreased total protein C and antithrombin

DIC was uncommon (18%)

142
Q

Which prostaglandin cause fever in hypothalamus?

A

Prostaglandin E2

143
Q

Dogs have how many days of neutrophils supply in bone marrow?

A

5 days

144
Q

True or False: Lymphopenia can be seen in both cortisol and epinephrine response.

A

False

Only cortisol response; epinephrine cause lymphocytosis

145
Q

What is MOA of aminoglycosides?

A

Bind to 30s ribosomal subunit → inpair protein synthesis

146
Q

How does the efficacy of aminoglycoside change when it is in an acidic and low oxygen tension environment?

A

Decreased efficacy

  • Not good for abscess
147
Q

True or False: Aminoglycoside should not be contained in the syringe with calcium.

A

True

No calcium, sodium bicarbonate or heparin

148
Q

Are aminoglycosides effective for anaerobic?

A

No

Their uptake across bacterial cell membranes depends on energy derived from aerobic metabolism

149
Q

How is aminoglycoside eliminated?

A

Excreted in the urine (predominately by glomerular filtration)

150
Q

What is single daily dosing regime for aminoglycosides?

A

The total daily dose is administered as a single dose about every 24 hours

151
Q

Aminoglycosides provide post-antibiotic effect (PAE). What is PAE?

A

Bacterial replication is impeded even after serum drug conc. have fallen below the MIC

152
Q

What is the target Cmax for aminoglycosides?

A

8 - 10 times of MIC

153
Q

How does aminoglycoside cause kidney injury?

A
  • Renal proximal convoluted tubules

The cationic state of the aminoglycosides facilitates binding to tubular epithelial cells → Intracellular transport → high concentrations of the aminoglycoside within lysosomes → Lysosomes destabilize and rupture → disrupts normal cell structure and function

154
Q

What is the MOA of fluoroquinolone?

A

Inhibit DNA gyrase or topoisomerase IV (both are enzyme-bound bacterial DNA complex) → inhibit normal bacterial DNA synthesis → bacterial cell death

155
Q

What are the primary target for fluoroquinolone in gram (+) and gram (-) bacteria?

A

Gram (+): topoisomerase IV
Gram (-): DNA gyrase

156
Q

Which generation is pradofloxacin?

A

3rd generation fluoroquinolone
Covers anaerobes as well

157
Q

True or False: Approximately 40% of marbofloxacin is excreted unchanged by the kidney.

A

True

158
Q

Resistance for fluoroquinolones - modalities

A
  1. efflux pumps
  2. gyrase and topoisomerase mutations
159
Q

Fluoroquinolones can cause seizures

A

True they compete with GABA in the CNS

160
Q

Marbofloxacin has the longest PAE and half life of all fluoroquinolones

A

True
PAE 8h
1/2 life 10h

161
Q

What is the MOA of sulfonamides?

A

It’s a competitive antagonist of PABA → disrupted bacterial folic acid synthesis → inhibit bacterial DNA synthesis

162
Q

What’s the most common preparation of sulfonamides?

A

Trimetroprim sulfa 1:5 (trim:sulfa)
Dose is combined

15mg/kg in a 8kg dog = 120mg (100mg of sulfa and 20mg of trim)

163
Q

Metabolism of sulfa

A

Hepatic
Elimination via urine with active metabolites (good choice for UTI)

164
Q

Why is enterococcus are naturally resistant to sulfonamides?

A

They can incorporate exogenously produced folate

165
Q

List 5 adverse effects for sulfonamides.

A

Anemia
Proteinuria/hematuria
Iatrogenic reversible hypothyroidism
KCS
Sulfonamide hypersensitivity (e.g. fever, polyarthropathy, hepatotoxicity, skin
eruptions, thrombocytopenia, neutropenia)

166
Q

What is MOA of macrolides?

A

Binds to 50s ribosomal subunit → inhibit protein synthesis

167
Q

Among all the antibiotics that inhibit protein synthesis, which one is bactericidal?

A

Aminoglycosides

168
Q

What is the target organisms of macrolides?

A

Gram (+)
Anaerobic
Mycoplasma

  • Azithromycin has better coverage to gram (-) compared to other macrolides
169
Q

What is the target organisms for metronidazole?

A

Anaerobic gram (+) and gram (-)

170
Q

Mechanism of action metronidazole

A

Nitroreductase produces active metabolite that disrupts bacteria DNA

171
Q

List 5 antibiotics that are bactericidal

A

𝜷-lactam
Aminoglycosides
Fluoroquinolone
Sulfonamides
Metronidazole

172
Q

What is the MOA of chloramphenicol?

A

Binds to 50s ribosomal subunits → inhibits protein synthesis

173
Q

List 1 advantage and 2 disadvantages for chloramphenicol.

A

Advantages:
1) Very broad-spectrum

Disadvantages:
1) Can cause bone marrow aplasia in human
2) Inhibit cytochrome p- 450 → decreases clearance of other drugs

Metabolised via glucuronidation so careful dosing in cats

174
Q

What is MOA of tetracycline? Is it bactericidal or bateriostatic?

A

Bind to 30s ribosomal subunit → inhibit protein synthesis
Bacteriostatic

175
Q

Tetracyclines are eliminated via ___ but ___

A

Intestinal route but they undergo extensive hepatic recyrculation

176
Q

What is the MOA of clindamycin? Is it bacteriostatic or bactericidal?

A

Bind to 50s ribosomal subunit → inhibit protein synthesis
Bacteriostatic

177
Q

Name 2 antibiotics that bind to 30s ribosomal subunit and 3 that bind to 50s ribosomal subunit.

A

30s: aminoglycosides, tetracyclines

50s: chloramphenical, macrolides, clindamycin

178
Q

True or False: Clindamycin also works for Toxoplasma gondii, Neospora caninum, Hepatozoon, and Babesia spp. but not gram (-) bacteria.

A

True

179
Q

What is the MOA of vancomycin?

A

Glycopeptide

Binds to the peptide precursors in the
bacterial cell wall → preventing cross-linking of peptidoglycan side chains → inhibit cell wall synthesis

180
Q

How is vancomycin metabolized?

A

Excreted through kidneys

181
Q

What is MOA of rifampin?

A

Block RNA polymerase

Bactericidal

182
Q

List 5 antibiotics that are time-dependent.

A

𝜷-lactam
Macrolides
Clindamycin
Tetracycline
Chloramphenical

183
Q

What is the coverage for vancomycin?

A

Gram (+) aerobic and anaerobic

184
Q

What are the two groups of antibiotics which their activity diminished by the presence of cations?

A

Fluoroquinolone
Aminoglycosides

185
Q

What are two groups of antibiotics that don’t work well in abscess?

A

Aminoglycosides
Vancomycin

186
Q

Name 4 antibiotics that don’t work well in acidic environment.

A

Aminoglycosides
Clindamycin
Fluoroquinolone
Macrolides

187
Q

What bacteria produces amphotericin B?

A

Streptomyces nodosus

188
Q

What is the MOA of amphotericin B?

A

Bind to ergosterol in fungal cell membranes → increased permeability → cell death

189
Q

What is the major adverse effects of amphotericin B?

A

Nephrotoxicity (binds to cholesterol in the proximal tubular cells → renal vasoconstriction & renal tubular acidosis)

  • To reduce nephrotoxicity, AMB usually is infused in 5% dextrose and administered intravenously over 1 to 5 hours
190
Q

What is the MOA of azole antifungal drugs?

A

Inhibit the fungal P-450, which is necessary for the development of ergosterol in fungal cell wall

191
Q

What are the two big group of azole drugs?

A

Triazole: itraconazole, fluconazole, voriconazole, posaconazole
Imidazole: ketoconazole, clotrimazole, enilconazole, miconazole

192
Q

What is the peak concentration for azole anti-fungal drugs?

A

6-14 days

193
Q

Which group of azole drugs have less effect on mammalian sterol synthesis and longer half life?

A

Triazole (itraconazole, fluconazole)

194
Q

Which azole anti-fungal drug is absorbed better with food and acid environment, and can be affected by H2 blocker, itraconazole or fluconazole?

A

Itraconazole

  • And ketoconazole
195
Q

Which azole anti-fungal drug has better penetration across BBB, blood-eye and blood-prostate barriers, itraconazole or fluconazole?

A

Fluconazole (water soluble, low protein-bound)

196
Q

If CNS is involved in a fungal infection, which anti-fungal drug should be used, itraconazole, ketoconazole or fluconazole?

A

Fluconazole

197
Q

How is fluconazole, itraconazole and ketoconazole metabolized/excreted, respectively?

A

fluconazole: minimal metabolism, renal excretion
itraconazole: cytochrome P-450
ketonazole: cytochrome P-450

198
Q

What is the drug of choice for histoplasmosis and cryptococcosis in the CCM?

A

Histoplasmosis: Itraconazole
Cryptococcosis: Fluconazole

199
Q

Mycoplasma spp do not have cell wall, so they are intrinsically resistant to which two types of antibiotics?

A

𝜷-lactam
Glycopeptides (e.g. vancomycin)

200
Q

True or False: Enterococcus is intrinsically resistant to aminoglycosides because the polar molecules can hardly penetrate the cell wall.

A

True

201
Q

What is the term of the movement of neutrophil across the capillary wall?

A

Diapedesis

  • diapedesis occurs through the interendothelial junctions of postcapillary venules
202
Q

What do the primary, secondary and tertiary granules contain in neutrophils?

A

Primary (azurophil): myeloperoxidases, defensins, lysosomal hydroxylase, neutral protease
Secondary (specific): metalloprotease
Tertiary (gelatinase): receptors for enhanced cellular communication

203
Q

There are two types of macrophages - M1 and M2. What are the function for each one of them?

A

M1
- Activated by inflammatory cytokines (TNF-𝜶, INF-𝛄)
- Produce pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and prostaglandins
- Phagocytosis
- Inhibit cell proliferation

M2
- Activated by anti-inflammatory cytokines (IL-4, IL-10, IL-13)
- Secrete growth factors (e.g. PDGF or TGF-β) → stimulate fibroblasts to produce collagen
- Promote cell proliferation and tissue repair

Both M1 and M2 macrophages secrete enzymes like collagenases and elastases to dissolve the extracellular matrix, facilitating phagocytosis and remodeling, respectively

204
Q

There are two types of T helper cells - TH1 and TH2. What cytokines do they secrete?

A

TH1
- Stimulated by IFN-γ and IL-12
- Produce IFN-γ and IL-2
- Function: maximize the bacterial killing potential of macrophages and stimulate proliferation of cytotoxic T-cells

TH2
- Stimulated by allergic reaction or helminthic infections
- Produce IL-4, IL-5, IL-10, and IL-13
- Function: increase in IgG1 and IgE production, and eosinophil activation.1

205
Q

Which two TLRs do LPS bind to?

A

TLR2, TLR4

206
Q

Which pattern recognition receptor does HMGB1 bind to?

A

RAGE

207
Q

Name 4 functions of TNF-𝜶.

A

1) Activate natural killer cells
2) Proliferate cytotocix T cells
3) Mediate T cell apoptosis
4) Produce proinflammatory cytokine (e.g. IL-6)
5) Produce oxygen reactive species, chemotaxis, and endothelial adhesion molecules

208
Q

True or False: IL-1ra, serves a counterregulatory function and is actually an antiinflammatory cytokine that competes with IL-1 for receptor sites.

A

True

209
Q

In IL-1 family what are the two substances that need to be complexed with IL-1𝜷 to activate cellular signaling pathway?

A

IL-1RI (a functional receptor)
IL-1 receptor accessory protein (IL-1RAcP)

210
Q

Which cytokines play a pivotal role in initiating hepatic synthesis of the acute phase proteins?

A

IL-6

211
Q

True or False: IL-6 is a pro-inflammatory cytokine.

A

True

But it also can initiate compensatory antiinflammatory responses and downregulating proinflammatory cytokine production.

212
Q

What are the three functions of IL-8?

A

1) Induce chemotaxis of neutrophils
2) Stimulate phagocytosis
3) Promote angiogenesis

IL-8 is also referred to CXCL8

213
Q

List 4 functions of IL-10.

A

1) depresses the production of cytokines (TNF-α, IL-1, IL-6, and IL-8), by inhibiting translocation of NFκB and promoting degradation of messenger RNAs
2) downregulates the production of Th-1 cytokines
3) promotes shedding of TNF receptors into the systemic circulation
4) inhibits antigen presentation by macrophages and dendritic cells

214
Q

How does steroid affect the arachidonic acid pathway?

A

Inhibits phospholipase A2

215
Q

Draw the arachidonic acid pathway.

A
216
Q

Which prostaglandin is a potent pyrogenic agent?

A

PGE2

217
Q

Which prostaglandin can cause uterus contraction?

A

PGF2

218
Q

Are Leukotriene B4, LTC4, LTD4, LTE4 proinflammatory or anti-inflammatory?

A

Proinflammatory

219
Q

Does leukotriene cause vasoconstriction or vasodilation?

A

Vasoconstriction

220
Q

True or False: The synthesis of platelet-activating factor is primarily modulated by mitogen-activated protein kinase (MAPK) intercellular signaling pathways.

A

True

221
Q

Where is platelet-activating factor from?

A

from cell membrane phospholipids metabolized by phospholipase A2

222
Q

Where is endogenous carbon monoxide from? Is it considered anti-inflammatory or pro-inflammatory?

A

Enzymatic breakdown of heme to bilirubin by heme oxygenases

Anti-inflammatory

223
Q

Where is endogenous hydrogen sulfide from? How does it work on the cells?

A

It is produced in tissues during cysteine metabolism (cystathionine β-synthase and cystathionine γ-lyase)

It works on ATP-dependent K+ channels, hydrogen sulfide relaxes smooth muscles and induces vasodilation.

224
Q

True or False: Bradykinin stimulates venous dilation through local nitric oxide release.

A

True

225
Q

What class of cytokine does substance-P belong to?

A

Tachykinin

226
Q

List 4 causes of hyperlactatemia during sepsis/septic shock.

A

1) Inadequate whole-body oxygen delivery
2) Impaired tissue oxygen extraction and the microcirculation
3) Increased glycolytic flux and Na,K- ATPase activity Through 𝜷2 stimulation
4) decreased lactate clearance

227
Q

What are the three main components of endothelial glycocalyx? Which one is the most abundant component?

A

Proteoglycans (PGs) - syndecans, glypicans
Glycoprotein (GPs) - selectins, immunoglobulins, integrins
Glycosaminoglycans (GAGs) - Heparan sulfate (HS), chondroitin sulfate (CS), dermatan sulfate (DS), keratin sulfate, hyaluronan (HA)

Glycosaminoglycans (GAGs) is the most abundant

228
Q

Which syndecan does endothelial glycocalyx mainly contain?

A

Syndecan-1

  • Syndecan is a transmembrane protein
229
Q

What are the two main selectins found in endothelial glycocalyx?

A

P-selectin (constitutively expressed and stored within Weibel-Palade bodies of the EC and platelets)
E-selectin

230
Q

Name 5 GAGs in endothelial glycocalyx. Which one is the most abundant on endothelial glycocalyx? Which one is not attached on the core protein and synthesized at difference place different from the rest?

A

Heparan sulfate (HS)
Chondroitin sulfate (CS)
Dermatan sulfate (DS)
Keratin sulfate
Hyaluronan (HA)

Heparan sulfate (HS) most abundant!

Hyaluronan (HA) → synthesized on the cell membrane

231
Q

True or False: Fibrinogen is not incorporated into the endothelial surface layer due to its large molecular weight.

A

False

It is incorporated into the ESL

232
Q

Explain the fiber matrix theory

A

The EG is formed by a matrix of fibers positioned 20nm apart in all dimensions which confers selectivity for particles with a diameter of less than 10nm (70KDa).
Selectivity is increased by the presence of molecules like albumin, fibrinogen, orosomucoid and GAGs.

233
Q

Give two examples of mechanotransduction in the glycocalix

A
  • HS is coupled with caveolae rich in NO
  • HA is coupled with CD44 which causes intracellular cascade and NO production
234
Q

Does Amoxicillin–clavulanate provide good anaerobic coverage?

A

Yes

235
Q

SIRS criteria

A
  • tachypnoea
  • tachycardia
  • WBCc derangements
  • temperature

Very poor specificity
In vet med no defined consensus on values

236
Q

Association of organ failure and mortality in dogs

A

compared with dogs with no organ failure, dogs with one organ failure had mortality odds of 6.7 vs dogs with three-four organs involved mortality odds 18.7

237
Q

Septic shock and mortality:
- fluid resistant hypotension + vasopressor + lactate >4 =
- fluid resistant hypotension + vasopressor + lactate > 2 = 42
- fluid resistant hypotension + vasopressor + lactate normal =
- hyperlactatemia >4 =
- hyperlactatemia > 2 =

A

49%
42%
30%
29%
26%

238
Q

According to a retrospective study on dogs with sepsis and MODS survival was correlated with number of organs involved in MODS:

A
  • no organs 84% survival
  • one organ 69%
  • two organs 46%
  • three organs 24%
  • four organs 9%
  • five organs 0%
239
Q

Sepsis biomarkers

A
  • pro-calcitonin: can differentiate healthy from critically ill dogs, but not SIRS vs Septic dogs. Recently shown that serial measurement had prognostic capacity to differentiate survivors vs non-survivors in a septic population
  • NLR not diagnostic or prognostic
  • cholesterol not prognostic or diagnostic
    *CNP produced by endothelium in response to cytokines –> pro-NCNP. Diagnostic but not prognostic (performance much improved when septic peritonitis dogs removed)
    *cell-free DNA not diagnostic but prognostic whennormalised to neutrophil count
240
Q

Sepsis induced myocardial dysfunction

A
  • NO
    vasodilation
    production of peroxynitrite that opens pores in mitochondria, cytochrome C out and death of myocytes
  • Ca channels
    downregulation of L-type Ca++ channels
  • endothelin
    vasoconstriction
  • inflammatory mediators
    TNF𝛼 and IL-1𝛽 both have negative inotropic effects
    Direct damage to desmosomes + neutrophils infiltration

+ systemic hypoperfusion, cytopathic shock, autonomic imbalance

241
Q

Dogs and cats can synthetise vit C in the liver

A

True

242
Q

Main functions of vit C

A
  • anti-oxidant
    *immuno-modulator
  • co-factor synthesis of catecholamine
  • improved response to catecholamines
    *co-factor in vasopressin synthesis
243
Q

Thiamine deficiency clinically presents in 3 phase manner

A
  1. lethargy, anorexia
  2. neurologic abnormalities
  3. terminal stage with coma and death
244
Q

Key functions of thiamine

A
  • synthesis of ATP –> hyperlactatemia
  • synthesis of ACh –> neuronal degeneration
  • anti-oxidant –> ROS
245
Q

Neutropaenia genetic causes

A
  • cyclic hematopoiesis (grey collie syndrome due to elane gene for elastase mutation - neutropenia every 10-14 days)
  • neutrophil trapped syndrome (collies)
  • myelodisplastic syndrome (mutated precursors can not develop further)
  • secondary dysmyelopoieis (similar to MDS but no increment in number of precursors)
246
Q

Type of resistance for beta lactamases:

A
  • mutation of PBP (i.e. mecA gene of MRSA)
  • beta-lactamases
  • efflux pumps
247
Q

Types of beta lactamases

A
  • extended spectrum beta-lactamases
  • penicillases
  • carbapenemase
  • AMPC-type cephalosporinase (plasmid)
248
Q

Time over MIC for different 𝛽lactams

A
  • 50% for penicillins
  • 60% for cephalosporins
  • 40% for carbapenems
249
Q

What’s the consideration when combining macrolides, chloramphenicol and clindamycin?

A

They all work on the 50S unit in very close-by sites, therefore they act as competitive inhibitors against each other

250
Q

List antibiotics to consider in MDR organisms

A
  • nitrofurantoin (nitrofuran reductase –> active metabolite –> extensive DNA damage. Causes severe side effects with hemolysis in cats and irreversible neuropathy in dogs)
  • vancomycin
  • rifampin (easy resistance so ALWAYS combined with another abx)
  • linezolid (Psite on 50s)
  • Daptomycin (forms ion channels leading to cell depolarization and death - highly toxic, can only be given IV with high risk of skeletal muscle damage in dogs)
251
Q

Infectious complications of IV catheters

A
  • irritation
  • inflammation/flebitis
  • catheter site infection (positive swab from skin)
  • catheter colonization (positive culture from catheter tip)
  • catheter-related blood stream infection (catheter tip culture matches blood culture) –> CRIBSI
252
Q

Catheter sparing diagnosis of CRIBSI

A

Ideally CRIBSI requires positive and matching cultures from catheter tips and blood, however if catheter is required to stay in place for patient’s management there are alternative ways by collecting blood samples from catheter and peripheral sites:
- time to posititvity (catheter site positive 2h earlier)
- differential quantitative (catheter site >5 x CFU than peripheral)
- single quantitative from catheter (>100CFU/mL)

253
Q

Treatment of CRBSI

A

If leaving catheter in place lock with high concentration solution of abx but DO NOT FLUSH into patient
Alternatively can rewire new catheter and start systemic abx.
If patient systemically unwell remove catheter and start IV wide spectrum antibiotics while waiting fur C&S

254
Q

Vasopressin is also produced by the kidneys

A

True

Recently vasopressin mRNA has been shown in the renal collecting ducts of mice and humans.
Its expression increases exponentially with hypernatremia and water deprivation.

255
Q

Terlipressin

A

Vasopressin analogue
lt is longer acting and more V1 specificity (V1/V2 ratio around 2.2 compared to Vasopressins 1:1 ratio).
Used in human medicine for hepatorenal syndrome.

256
Q

Is there any benefit in combining corticosteroids and vasopressin in septic patients?

A

VASST Trial showed that they might be synergistic and indicated reduced mortality when the two agents are given in combination.
Vasopressin without steroids it was associated with increased mortality vs combo.

257
Q

Push dose of vasopressin?

A

Used mainly in anesthesia, but can be useful to see if patient would respond to CRI (VALOR study: MAP increase >22 mmHg within 3-5 minutes after push).
Careful using in peripheral lines as if extravasate can cause very severe tissue damage and necrosis.

258
Q

Which patients can particularly benefit from vasopressin administration?

A

Septic patients and heamorrhagic shock patients (exhaustion of pituitary stores)
Hepatorenal syndrome
Patients on ACEi and ARBS

259
Q

Name the three key players in the “dysregulated host response” in septic patients

A
  • Endothelium
  • Immune system
  • Coagulation system
260
Q

List 5 pathophysiologic responses of the immune system to sepsis that crossover with the coagulation system
“thrombo-inflammation”

A
  1. Neutrophils activation and NETs formation
  2. Formation of microvescicles and exposure of TF and PS eliciting pro-coagulant and pro-inflammatory response
  3. co-localization of MV+NET activating the kallykrein system (coagulation + inflammation)
  4. Interaction of NETs with platelets (pro-coagulant and pro-inflammatory) - remember plts can express TLR-4 and activate neutrophils and complement
  5. Release of DAMPs and HMGB-1 from damaged cells (pro-coagulant and pro-inflammatory)
261
Q

Endothelial response to sepsis - list 3 key points

A
  1. glycocalyx shedding (exposure of pro-coagulant surface)
  2. ADAMTS-13 consumption (more large polymers of vWf)
  3. expression of I-CAM and VICAM
262
Q

List 3 major coagulation system derangement in sepsis

A
  1. defective fibrinolysis due to increased PAI-1 and TAFI (unknown mechanism) and degradation od plasminogen by neutrophils’ elastases
  2. decreased protein C, protein S and antithrombin
  3. platelets interaction with inflammatory cells and complement promote their activation and aggregation
263
Q

What is SIC?

A

Sepsis-induced coagulopathy, which is an early stage of DIC.
Important to diagnose as it as poor prognostic factor (HYPRESS study mortality was almost double in patients with SIC vs without).

264
Q

Criteria to diagnose SIC

A
  • qSOFA
  • PT
  • Platelet count
265
Q

AKI incidence is higher in patients with DIC

A

True

The distinct renal vasculature architecture makes the kidneys particularly susceptible to microthrombus formation

266
Q

Effect of angiotensin II, norepinephrine and vasopressin on inflammation and immune system

A

Angiotensin II augment the immune response in sepsis while norepinephrine and vasopressin have predominantly anti-inflammatory effects that contribute to sepsis-induced immunoparalysis

267
Q

Are IVIG recommended as an ancillary treatment in sepsis according to the 2021 SSC guidelines?

A

No, as there is not enough evidence to support their use.
Theoretical benefit would be B/T cell immune modulation.

268
Q

Is heparin administration recommended in septic patients?

A

No, large randomised trials have failed to show any survival benefits with an increased risk of bleeding.

269
Q
A

ECVECC Board Exam (24 decks)

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