Endotoxemia and SIRS in horses Flashcards
Inflammation is
a normal physiologic response to tissue damage.
Can be caused by damage from:
mechanical
environmental
toxic
chemical
pathogenic
Why does the body produce inflammation? (3)
Eliminate pathogens
Restore damaged tissue
Release of inflammatory mediators that are needed for resolution of damage.
Basic steps of initiaiton of inflammation. (3)
- Innate immune cells recognize a threat to the host
- Inflammatory mediators are upregulated and released
- Local and circulating mediators cause local and systemic inflammatory reactions by the host
SIRS stands for?
What is SIRS?
systemic inflammatory response syndrome
Is a non-specific, clinical, pro-inflammatory immune response. Its a clinical syndrome.
Why and what happens?
Inflammatory mediators produced in massive quantities in multiple sites.
Mediators circulate throughout the body and cause tissue damage at sites far from initial inflammatory insult.
Stages of SIRS.
Stages 1-3
Stage 1. A local reaction at the site of injury that aims at containing injury and limit spread.
Stage 2. Early CARS -> compensatory anti-inflammatory response syndrome.
Stage 3. Local reaction becomes systemic, inflammatory reaction is too strong and uncontrollable.
Describe stage 1 of SIRS
Stage 1. A local reaction at the site of injury that aims to contain injury and limit spread by:
- Activation of innate immune system (macrophages) and release of cytokines
- Vasoactive phase (vasodilation): vascular permeability increases and neutrophils are transfered into tissue space
- Neutrophils and monocytes gather in site of infection, active phagocytosis
Describe stage 2 of SIRS
Stage 2. Early CARS -> compensatory anti-inflammatory response syndrome: the body’s attempt to maintain immunological balance.
Describe stage 3 of SIRS
Stage 3. Local reaction becomes systemic, inflammatory reaction is too strong and uncontrollable:
- Progressive endothelial dysfunction
- Coagulopathy and activation of coagulation pathway (eventual DIC)
- Disturbance in microcirculation, microthrombosis (DIC), systemic hypotension
- Loss of circular integrity
- Inflammatory mediators affect local somatosensory nerves and cause pain sensation – this causes brain stem to activate spleen and thymus which release more leukocytes and increase production of cytokines.
Sepsis can be defined as?
As opposed to “severe sepsis”?
The presence of infection (documented or strongly suspected) with a systemic inflammatory response.
Severe sepsis is sepsis that is associated with organ dysfunction, hypoperfusion, or hypotension.
Septic shock =
Severe sepsis complicated by acute circulatory failure characterized by persistent arterial hypotension, despite adequate volume resuscitation, and unexplained by other causes.
May not respond to aggressive fluid therapy like one would expect basic hypovolemia/hypotension to do.
MODS =
MOF =
MODS = multiple organ dysfunction syndrome
Presence of altered organ function in an acutely ill patient such that homeostasis cannot be maintained without intervention.
MOF = multiorgan failure
Irreversible organ dysfuntion.
SIRS is sick, MODS is sicker and MOF is dying
Endotoxemia can be defined as
SIRS that is caused by endotoxin in the blood stream.
Bacterial lipopolysaccharide (LPS) is the most common to cause SIRS in horses. Even a small dose will cause SIRS.
Originates from the outer cell membrane of G-neg. bacteria upon the bacteria’s death and reproduction.
G-neg. bacteria is from the environment and from the GI tract.
Describe bacterial endotoxin lipopolysaccharide.
Released from gut into bloodstream
- Normally found in very low concentrations
- More after exertion (racehorses, endurance horses)
- Normally small amounts are cleared by Kupffer cells in the liver
Too much endotoxin overwhelms the liver’s clearance capacity thus bypasses the liver.
E.g. in cases of colic or intestinal torsions, a large amount of bacteria die in the gut and release loads of endotoxin which overwhelm the body.
What is the physiological result of SIRS/sepsis/endotoxemia? (6)
Systemic drop in blood pressure and cardiovascular collapse.
Cardiac contractility decreases, systemic vasodilation occurs.
Thrombosis of small vessels can occur.
Arterial hypoxemia occurs.
Organ perfusion disturbance and organ ischemia results in cellular dysfunction. Especially: liver, kidneys, brain, heart, GIT.
Finally the patient dies.
Cells with highest oxygen requirement/metabolic rate most affected.
The ultimate cause of death in SIRS/sepsis/endotoxemia? (3)
Cardiovascular failure
Lack of oxygen delivery to the tissues
plus Secondary complications (e.g. laminitis)
What type of equine patients have a higher risk of developing SIRS/endotoxemia? (6)
- Colic patients – e.g. GIT ischemia, enteritis, colitis
- Peritonitis cases (especially fibrinous cases)
- Pleuropneumonia cases
- Severe bacterial metritis – e.g. retained fetal membranes
- Large intestinal acidosis - carbohydrate overload
- Foals!
Why are foals at higher risk of developing SIRS/endotoxemia? (2)
Due to failure of transfer of immunoglobulins which is the most common reason for the foal to be admitted to the hospital.
Overwhelming local bacterial infection occurs such as umbilical remnant infection, pneumonia, diarrhea.
Septic arthritis, pneumonia, umbilical infection, (renal dysfunction) are common in foals and each may cause the other as the bacteria travel along the blood stream.
SIRS criteria depends on age.
Adult SIRS criteria (two or more of the following): (4)
Body temperature < 36,6°C or > 38,6°C
Tachycardia > 60 beats/min
Tachypnea > 30 breaths/min or PaCO2 < 32 mm Hg
Leukocyte count< 4000/μL or > 12,500/μL or ≥10% band cells (leukopenia or leukocytosis)
Allow the horse to calm and cool before checking the status or else it may be inaccurate.
SIRS criteria depends on age.
Neonatal (up to 3 days old) SIRS criteria for foals: (7)
Criteria for neonates requires 3 or more of the following, 1 of which must be abnormal temperature or leukocyte count:
Body temperature < 37,2°C or > 39,2°C
Leukocyte count < 6900/μL or > 14,400/μL or ≥5% band cells
Tachycardia > 115 beats/minute
Tachypnea > 56 breaths/minute
Venous blood lactate level > 5,0mmol/L
Venous blood glucose level < 50mg/dL
Evidence of sepsis, cerebral ischemia or hypoxia, or trauma.
If a foal’s HR is under 60 bpm, its decompensating and very poorly.
Clinical signs of SIRS/sepsis/endotoxemia. (7)
- Hyperemic or injected mucous membranes with or without a toxic line (this is a purple rim just above the gingival line on the upper incisors is an accumulation of toxins in peripheral blood vessels).
- Rapid or prolonged capillary refill time (CRT)
- Rapid in early stage
- Peripheral vasoconstriction
- Later vasodilatation
Petecchiation or ecchymoses
- Capillary damage from inflammatory cells,
- Platelet dysfunction or secondary coagulopathy
Cool distal extremities (really bad in foals!)
Poor peripheral pulse quality
Delayed jugular filling
Edema of distal limbs, ventral abdomen
- Indicates increased vascular permeability
Hematological lab findings in SIRS/sepsis/endotoxemia. (3)
Leukocytosis (later stages when the body has produced more leukocytes) or leukopenia (in early stages, they chemotax to site of inflammation)
Left shift (toxic changes in neutrophils)
Hemoconcentration due to loss of plasma volume
Biochemical lab findings in SIRS/sepsis/endotoxemia. (5)
Liver enzymes: GGT may be elevated
Urea, crea (kidney values): may be elevated
- Pre-renal azotemia due to hypovolemia and perfusion disturbance common.
- Later, acute kidney injury develops.
Lactate
- May be elevated due to decreased tissue perfusion.
SAA, major acute phase protein in horses
- Some evidence that infections induce stronge SAA response.
Fibrinogen elevated
+ coagulopathies!
Coagulopathies seen in SIRS/sepsis/endotoxemia. (3)
Thrombocytopenia
Increased prothrombin time (PT),
increased partial thromboplastin time (PTT)
NB take coag samples into citrate tubes!
Tx points of SIRS/sepsis/endotoxemia. (7)
Support cardiovascular system – FLUID THERAPY!
Control infection (if present)
Inhibit endotoxin release into circulation
Inhibit immune cells activation by LPS
Inhibit mediator synthesis
Reduce the effects of inflammation
Prevent hypercoagulation
80-100 L/day for a 500 kg horse
Example pic: Ringer’s, GLU infusion, inotrope/vasopressor dobutamine infusion, K+, insulin
