Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
70 Cards in this Set
- Front
- Back
What is the definition of sepsis?
|
The systemic inflammatory response to infection
|
|
What is the main difference b/w endotoxemia and sepsis?
|
*Endotoxemia refers only to LPS in the blood
|
|
What are some examples of common sources of sepsis? (5)
|
1) Metritis
2) Pneumonia 3) Pleuritis 4) Septic peritonitis 5) Enteritis & colitis |
|
What is the definition of endotoxemia?
|
Only refers to circulating lipopolysaccharide found in gram negative bacteria's cell wall
|
|
What large animal is very sensitive to endotoxemia?
|
Horses
|
|
What is the definition of SIRS?
|
An inflammatory response to a variety of clinical insults manifested by two or more of the following: increased heart rate, increased respiratory rate, increased or decreased body temperature, increased or decreased WBC (or demonstratable left shift w/ >10% immature neutrophils)
|
|
What is CARS?
|
Compensatory anti-inflammatory response syndrome
|
|
What can SIRS result in if CARS doesn't balance it out?
|
MODS: multi organ dysfunction syndrome
e.g. have pleuritis, but now dealing with renal failure |
|
Are hooves considered part of MODS?
|
YES! hooves can get laminitis- hooves are considered an organ
-counts against us when looking at number of organs failing and hence prognosis |
|
What causes SIRS?
|
Body has it's normal response to inflammation, but then goes overboard (overproduction of pro-inflammatory cytokines)---> SIRS
|
|
What is the body's response to SIRS?
|
CARS: supposed to be a balance b/w CARS and SIRS
|
|
How can you tell when an animal's CARS is actually the one causing problems and not SIRS?
|
When CARS is too intense the animal becomes immunosuppressed = can contribute to mortality in ICU
|
|
How do you determine if an animal fits the definition for sepsis?
|
Look at biomarkers
-things like LPS binding protein -endotoxin activity -procalcitonin *Lots of different ones out there- very few actually give information on sepsis or prognosis |
|
What is the definition of severe sepsis?
|
Sepsis with at least one organ dysfunction or hypoperfusion
e.g. horse that comes in w/ colitis and diarrhea and start having changes in renal values and the next thing you know the horse has laminitis -poor prognosis |
|
True or false. More often than not its the secondary diseases that end up killing animals with severe sepsis.
|
True
|
|
What does the survival of animals with sepsis depend on?
|
The number and severity of complications associated with the sepsis
|
|
What is the definition of septic shock?
|
Severe sepsis w/ hypotension that is resistant to adequate fluid resuscitation
-no matter how many fluids you give you can't bring pressure up so have to use vasopressors |
|
What is the definition of bacteremia?
|
The presence of viable bacteria in the blood stream
-Get a positive blood culture |
|
What is the definition of MODS (Multi-organ dysfunction syndrome)?
|
Impairment of two or more organ systems in an acutely ill patient where homeostasis cannot be maintained without therapeutic intervention
|
|
What is the starting point of sepsis?
|
Stimulation of the *innate immune response
|
|
The molecules involved in the innate immune response, which results in sepsis have recently been termed __________.
|
DAMPs: damage-associated molecular pattern
|
|
What are 3 DAMPs?
|
1) The invading organism (bacteria, virus, fungus etc) origin molecules
2) PAMPs: pathogen associated molecular pattern 3) Alarmins -calprotectin, proteins released from damaged cells |
|
What receptors involved with the systemic inflammatory response recognize specific PAMPs?
|
Toll-like receptors (TLRs) and Nucleotide binding oligomerization domain (NOD) receptors
-Thus, there are a host of TLRs that recognize microbial components ranging from double-stranded viral RNA to LPS and peptidoglycan components of bacterial cell walls |
|
TLRs play an important inflammatory role in multiple cell types including ________.
|
Epithelial cells
|
|
What is the purpose of TLRs? How do they play a role in sepsis?
|
Designed to be protective and eliminate the pathogen, cause cytokine release
-but when inflammatory response is overzealous and becomes systemic it can have deleterious effects on the body |
|
What is the first cytokine that comes to mind when you think of viruses?
|
Interpheron
|
|
The most common source of equine endotoxemia/ sepsis is the __________.
|
Gastrointestinal tract
|
|
What type of bacteria are present in the small and large intestine?
|
-Small intestine: documented as a prominent source of endotoxin-containing coliform bacteria
-Large intestine: also has high concentrations of other types of bacteria such as Streptococcus species and multiple anaerobic species |
|
Is endotoxin the only molecule that causes inflammation on gram-negative bacteria in the GI tract?
|
Nope, other molecules such as flagellin, peptidoglycan and bacterial DNA itself can cause inflammation
|
|
What is the intestinal mucosa's role in preventing sepsis? (2)
|
1) Plays a critical role as a barrier to limit bacteria and/or their toxins from being absorbed into the systemic circulation
2) Part of body's innate immune defense against sepsis |
|
**What is absorbed when the intestinal barrier is disrupted in a horse with gastrointestinal disease?
|
Not only endotoxin but a cocktail of multiple gram positive and gram negative toxins from aerobic and anaerobic bacteria
-makes term endotoxemia somewhat naive to explain syndrome -may account for failure of drugs specific to circulating endotoxin to address sepsis |
|
True or false. It is abnormal to have the presence of endotoxins in the equine gastrointestinal tract.
|
False, there are GRAMS of endotoxin in the equine GI tract
-yet micrograms can trigger a response |
|
Give a general summary of how sepsis can result in a horse with severe colitis.
|
Alteration in normal mucosa think of all the bacteria & protozoa in there), think of parvo puppy, salmonella in adult cow, e coli in cows all = alteration in mucosa so function is altered & normal protection, inflammation so normally tight junctions are loser====> absorb toxins from GI tract (**not just endotoxin!!!)====> trigger to start the whole process! get inflammation and this takes off: either stay in appropriate area on graph or do we have too much of SIRS or CARS
|
|
Regardless of the initiating factor of sepsis-related disease processes, the clinical result is what 4 deficits?
|
1) Deficits in tissue perfusion
2) Obtundation 3) Ileus 4) Increased risk of laminitis |
|
What are 4 initiating factors of sepsis?
|
1) Endotoxin
2) Other bacterial components 3) breakdown products of endogenous proteoglycans 4) Polypeptides arising from the intestine |
|
Several mediators have been implicated in the sepsis-related disease process. What are the 4 cells that produce these mediators?
|
1) Mononuclear phagocytes, including monocytes in peripheral blood
2) Peritoneal macrophages 3) Pulmonary intravascular macrophages 4) Tissue-fixed macrophages -recent studies also implicate neutrophils and more specifically interactions b/w monocytes and neutrophils |
|
Explain the clinical cycle that is seen with sepsis?
|
-poor tissue perfusion (extended CRT)-----> look at mentation (obtunded animal)
-decreased GI sounds (ileus starts to develop) -laminitis has to be on radar when dealing with a horse that's severely sick (colitis, pleuritis, etc) |
|
What are the first immune cells that responds to sepsis-related disease processes?
|
Macrophages, monocytes, pulmonary intravascular macrophages (PIMs)
|
|
How are the lungs really important in the initial response to endotoxins & toxins in the GI tract?
|
Pulmonary intravascular macrophages (PIMs) are important in initial response
|
|
Of the numerous inflammatory mediators that have been identified as being related to sepsis, what are the 2 most common?
|
1) TNF alpha
2) Prostaglandins |
|
When are the cytokines such as TNFa and interleukins (IL-1) synthesized and released when exposed to endotoxins?
|
Released relatively early and exert their effects by altering the expression of other inflammatory genes, after first binding to specific receptors on target cells
|
|
Collective cytokine due to endotoxin exposure results in initiation of what 4 things?
|
1) fever
2) Alterations in leukocyte function 3) Activation of coagulation 4) Acute phase response component of systemic response to endotoxins |
|
When do TNFalpha concentrations peak in response to endotoxin?
|
Peak serum concentrations detected in 1-2 hours
|
|
What are 2 interleukins that are important pro-inflammatory agents?
|
IL-1
IL-6 |
|
What is an important anti-inflammatory interleukin?
|
IL-10
|
|
What is the function of IL-8?
|
Responsible for cell migration, starts drawing neutrophils to area
-normal response unless overzealous |
|
Cyclo-oxygenase-derived metabolites of ___________ are involved in the response of horses to endotoxemia.
|
Arachidonic acid
|
|
Endotoxemia is associated with a rapid increase in circulating concentrations of stable metabolites of _______ and ______.
|
Prostaglandins and thromboxanes (faciitates aggregation, vasoconstrictor)
|
|
How can you interfere with the process of metabolites of arachidonic acid causing endotoxemia?
|
Early administration of potent non-steroidal anti-inflamatory drugs (such as flunixin meglumine) reduces the hemodynamic and clinical response to endotoxin as well as plasma concentrations of arachidonic acid metabolites
|
|
Do endotoxins directly make a horse ill?
|
No, endotoxin is merely a potent trigger of the horse's inflammatory response, and it is the response that ultimately makes the horse ill
|
|
How can endotoxins initiate a systemic inflammatory response?
|
Have one of many pathogen associated molecules patterns (PAMPs) that are recognized by horse's innate immune system
|
|
What is the best way to identify/ diagnose sepsis?
|
Currently best identified/ diagnosed on the basis of fulfillment of criteria for SIRS in the presence of a suspected or confirmed infection
|
|
There is no consensus definition of sepsis in large animal patients. How is SIRS diagnosed in large animal patients?
|
On the basis of meeting 2 or 3 out of 4 of the following clinical criteria: abnormal temperature, heart rate, respiratory rate or a change in the leukon (leukocytosis, leukopenia, or significant left shift)
|
|
A large animal fits the criteria for SIRS, what diagnostic work-up should be done now?
|
-evaluate for evidence of infection
-evidence using culture and cytology (intracellular bacteria) - Imaging (thoracic radiographs, abdominal ultrasound) |
|
What is a useful biomarker currently in clinical veterinary practice?
|
The blood to abdominal fluid glucose and lactate differential
|
|
What are the 4 things that we try to direct our therapy for sepsis/ endotoxemia towards?
|
1) Circulatory support
-**fluids (most important) 2) Remove cause of sepsis/ endotoxemia (if you can) -e.g. strangulating intestine--> damaged mucosa, fix strangulation 3) Neutralize circulating endotoxin 4) Inhibit endotoxin induced inflammation ***START W/ FLUID & SUPPORT |
|
What drugs can we use to neutralize circulating toxins in sepsis cases?
|
-Banamine (one of the best)
-steroids -lidocaine (shown to work on peritonitis, but not all body systems e.g laminitis) |
|
What are the 3 goals of fluid therapy in a horse with endotoxemia?
|
1) Replacement of deficits
-volume resuscitation -rehydration 2) Provision for maintenance needs 3) Provision for on-going loses *polyionic fluids w/ K+ supplement & other supplements if indicated |
|
How do we correct acidemia in a patient with endotoxemia?
|
volume expansion using an alkalinizing solution
|
|
What are 3 alkalinizing solutions that can be used to correct acidemia in large animals?
|
1) Lactated ringers solution or Normosol-R
2) Bicarbonate supplementation may be necessary 3) Hypertonic saline solution helps restore circulatory volume & then followed by isotonic solutions |
|
What are 2 colloidal fluids that can be used in a horse w/ endotoxemia?
|
1) Plasma
-maintain total solids > 4.0g/dL -Benefit from other protein constituents (AT III, fibronectin) 2) Hetastarch (10ml/kg/day) |
|
Why do we give NSAIDs to a horse with endotoxemia? What NSAID do we like to give?
|
Analgesia and anti-endotoxic effects
-Flunixin meglumine |
|
What type of agent is pentoxfylline? How does it work?
|
Rheologic agent
-decreases platelet aggregation and TNF and IL-1 in vitro (important mediators of endotoxemia) |
|
How is pentoxfylline administered? Why?
|
HAVE TO GIVE IV FORM
-low bioavailability if administered orally in the horse |
|
When should aspirin be administered to a horse with endotoxemia?
|
When have thrombotic disorders (DIC)
|
|
What are 3 reasons to administered heparin to a horse with endotoxemia?
|
1) Laminitis prevention?
2) W/ plasma promotes AT-III activity 3) DIC |
|
What's the purpose of administering polymixin B to a horse with endotoxemia?
|
Binds endotoxin
-clinical evidence of efficacy? -caution when administering to azotemic patient |
|
What are 2 cases when antimicrobials should be used in horses with endotoxemia?
|
Bacteremia
Immunosuppression is present |
|
What are 2 antimicrobial protocols that can be used in horses with endotoxemia?
|
1) Aminoglycosides and penicillin commonly used
-penicillins may predispose to clostridial colitis 2) Metronidazole -anti-inflammatory effects |
|
What is volume resuscitation? Compare to rehydration.
|
Resuscitation: rapid, initial volume replacement, the initial 1-2 hours of time; hydration occurs over hours of time after you have performed fluid resuscitation (after this perform fluid maintenance)
|