- Toxemia is caused by widespread activation of the host defense system in response to toxins produced by bacteria or tissue injury. Endotoxemia specifically refers to toxemia caused by lipopolysaccharide components of gram-negative bacteria in the blood. - Endotoxemia can cause abnormalities in multiple body systems including cardiopulmonary, hematologic, gastrointestinal, and others. This can progress to endotoxic shock with severe hypotension. - Treatment of endotoxemia focuses on removing infection sources, antibiotics with gram-negative coverage, aggressive fluid therapy, and inhibiting inflammatory pathways. Despite treatment, endotoxemia carries a high fatality rate.

1. TOXEMIA AND ENDOTOXEMIA
Dr Arun Mourya

2. TOXEMIA AND ENDOTOXEMIA
• Toxemia is a clinical systemic state caused by
wide spread activation of host defense
mechanism to the presence of toxins
produced by bacteria or injury to tissue cell.
• Toxemia does not include the diseases caused
by toxic substances produced by plants or
insects or ingested organic or inorganic
poisons.

3. • most common form of toxemia in animals, caused by the
presence of lipopolysaccharide cell-wall components of gram-
negative bacteria in the blood and characterized clinically by
abnormalities of many body systems.
 Marked alterations in cardiopulmonary function
 Abnormalities in the leukon (neutropenia and lymphopenia)
and thrombocytopenia that may lead to coagulopathies
 Increased vascular permeability
 Decreased organ blood flow and metabolism, leading to heart
and renal failure
 Decreased gastrointestinal motility
 Decreased perfusion of peripheral tissues, leading to shock
 The need for intensive and complex therapy
 A high case fatality rate

4. ETIOLOGY
ANTIGENIC TOXIN
EXOTOXINS
CLOSTRIDIUM
SPP
ENDOTOXINS
LPS E coli
ENTEROTOXINS
E coli intestine
MM
METABOLIC
ABNORMAL
METABOLISM
INCOMPLETE
ELIMINATION

5. PATHOGENESIS
Endotoxins are normally present in the intestine and, although the intestinal
mucosa provides a highly efficient barrier, limiting transmural movement of
endotoxins, small quantities are absorbed into the portal blood.
These endotoxins are removed by the liver and do not reach the peripheral
blood
HEPATIC FAILURE AND DISRUPTED MUCOSAL BARRIER
(Ischemia, trauma, ionizing radiation, bacterial overgrowth,
Decrease ruminal pH, or inflammatory intestine disease)
Once the endotoxins gain access to the blood, they are removed from the
circulation by the mononuclear phagocyte system,
the response of these phagocytes to the lipopolysaccharides determines the
severity of the clinical illness.

6. Cardiopulmonary function
Early stage:
• heart rate and cardiac output commonly increase,
• although systemic blood pressure remains near or slightly less than normal
• Oxygen demands of peripheral tissues are increased during the hyperdynamic
phase
• resulting in compensatory mechanisms that increase blood flow in an attempt
to meet the increased metabolic demands
• blood flow still may be inadequate to meet the needs of tissues in a hyper
metabolic state
• Hyperventilation
• Decrease CRT
• Red congested mucus membrane
• Microcirculatory shunting of blood continues in organs such as the
gastrointestinal tract and kidney
• Ischemia of intestinal mucosa is manifested clinically by ileus and diarrhea may
occur
• Decreased renal perfusion will result in decreased urine output.

7. • With uncontrolled endotoxemia, the hyperdynamic phase progresses to
the hypodynamic phase of shock
• decreased cardiac output,
• systemic hypotension,
• Increased peripheral resistance,
• decreased central venous return
• Hypothermia,
• rapid irregular pulses,
• prolonged capillary refill time,
• pale to cyanotic mucous membranes,
• acidemia, and hypoxemia
• skin and extremities are cool
• Severe pulmonary edema
• increasing pulmonary hypertension
• Neutropenia due to leucocyte margination and sequestration
• Haemoconsontration due to movement of fluid from the vascular to
extravascular space.

8. Hemostatic System
• Endotoxins cause endothelial injury directly or indirectly
• exposing sub endothelial collagen and tissue thromboplastin,
initiating the intrinsic and extrinsic coagulation cascades,
respectively.
• Endotoxin can initiate the coagulation cascade directly by activation
of factor XII or by inducing platelet release of thromboxane and
other procoagulant substances.
• Endotoxin may induce coagulopathy indirectly by endothelial
damage with secondary factor XII activation, or through the effects
of complement activation
• Macrophages and leukocytes have been shown to release a
procoagulant substance in response to endotoxin, which functions
similarly to factor VII and may also have a role in perpetuating
coagulopathy in endotoxemia via the extrinsic pathway

9. • The principal clinical finding of DIC in horses is petechial
and/or ecchymotic hemorrhages on mucous membranes and
sclerae with a tendency to bleed from venipuncture sites
• The result of exaggerated thrombin formation during DIC is
widespread fibrin deposition in the microcirculation causing
circulatory obstruction and organ hypoperfusion that may
lead to ischemic necrosis and failure.
• Leads to multiple organ failure and death.

10. Thermoregulation
Bacterial endotoxins are potent stimulators of macrophage
interleukins
• Fever
• Increase no. & immaturity of circulating neutrophils
• Increase Muscle proteolysis through increase Prostaglandin E2
• Increase hepatic acute phase protein production
• Decrease albumin synthesis
• IL6 concentration lower in colostrum deprived calf.

11. Gastrointestinal function
• Inhibition of GIT motility (Stomach, SI and LI)

12. Carbohydrate metabolism
• ↓ in plasma glucose concentration
• Disappearance of liver glycogen
• ↓ glucose tolerance of tissue so that administered
glucose in not used rapidly
• Endotoxic shock can result in lactic acidemia and both
hyper & hypo glycemic responses
• Hyperglycemia: occur early & transiently accompanied
by ↑ rate of glucose production & is depend on
mobilization of glycogen
• Hypoglycemia: very common in prolonged & severe
endotoxiemia

13. Protein metabolism
• ↑ in tissue breakdown (catabolism)
• ↑in BUN
• ↑ globulin & ↓ albumin as a part of acute
phase reaction.

14. Mineral metabolism
• Negative mineral balance
• Hypoferremia and hypozincemia as a part of
acute phase reaction
• Blood Cu ↑

15. Reproduction and Lactogenesis
Endotoxemia can cause pregnancy failure in
domestic animals, particularly when pregnancy
is corpus luteum–dependent.
In horses and cattle, experimentally induced
endotoxemia causes an immediate and
pronounced release of prostaglandin F2α

16. Combined Effects on Body Systems
• The combined effects of the hypoglycemia, hyper l-
lactatemia, and acidemia
• interfere with tissue enzyme activity and reduce the
functional activity of most tissues.

17. CLINICAL FINDINGS
Acute toxemia :
• The clinical findings of acute toxemia in most nonspecific
toxemias are similar.
• The syndrome varies with the speed and severity of the toxic
process but the variations are largely of degree
• Depression, anorexia, and muscular weakness are common in
acute endotoxemia
• Calves do not suck voluntarily and may not have a suck reflex.
• Scant feces are common but a low-volume diarrhea may also
occur

18. CLINICAL FINDINGS
• The heart rate is increased and initially the
intensity of the heart sounds is increased, but
later as the toxemia worsens the intensity may
decrease.
• The pulse is weak and rapid but regular.
• A fever is common in the early stages of
endotoxemia but later the temperature may be
normal or subnormal.
• In neonatal calves, foals, and lambs a fever may
not occur because of failure of thermoregulation
or deprivation of colostrum.

19. CLINICAL FINDINGS
• Terminally, there is muscular weakness to the point of
collapse, and death occurs in a coma or with
convulsions
• Anterior uveitis, manifested as lacrimation,
blepharospasm, photophobia, corneal edema,
conjunctival hyperemia, and fibrin in the anterior
chamber are commonly present in septicemic foals.
• Posterior segment lesions, such as multifocal
hemorrhages, exudates, and focal retinal detachments
may also be visible during ophthalmic examinationin
foals with minor anterior segment changes
• The presence of uveitis is associated with a lower
survival rate in foals

20. CLINICAL FINDINGS
Endotoxemia: When toxin formation or liberation into
the circulation is rapid and the toxicity of the toxin high
enough, the onset of cardiovascular collapse is rapid
enough to cause a state of toxic or septic shock.
• Severe peripheral vasodilatation with aconsequent fall
in blood pressure
• Pallor of mucosa
• Hypothermia
• Tachycardia
• Pulse of small amplitude
• Muscle weakness

21. Chronic Toxemia
• Lethargy,
• separation from the group,
• inappetence,
• failure to grow or produce,
• emaciation

22. CLINICAL PATHOLOGY
Hematology:
• Changes in total and differential leukocyte
Numbers Leukocytosis and neutrophilia occur
with mild endotoxemia
• leukopenia, neutropenia, and lymphopenia
increase in severity and duration with
increasing severity of endotoxemia.

23. Serum Biochemistry
• low plasma glucose concentration
• High serum urea concentration
• low serum albumin and total protein
concentration
• Decreased albumin and total protein
concentrations are in response to increased
capillary permeability
• whereas the azotemia reflects a decreased
glomerular filtration rate.

24. TREATMENT
Principles of treatment of endotoxemia or septic
shock include
(1) removal of the foci of infection;
(2) administration of antimicrobial agents with a
gram-negative spectrum;
(3) aggressive fluid and electrolyte therapy to
combat the relative hypovolemia, systemic
hypotension, hypoglycemia, and electrolyte and
acid-base disturbances; and
(4) NSAIDs or glucocorticoids for the inhibition of
products of the cyclooxygenase pathway.

25. TREATMENT
A beneficial response is noted by the following:
• Correction of peripheral vasoconstriction
• Restoration of an acceptable pulse quality
• Return of urine output
• Increase in the central venous pressure
• Restoration of mean arterial blood pressure to
>65 mm Hg
• Restoration of cardiac output
• Restoration of oxygen delivery to acceptable
levels

26. TREATMENT
Glucose and Insulin
administration of glucose(37 mg/kg/h, equivalent to 30
kcal/kg/day)and insulin (0.07 U/kg/h) as continuous rate
infusions is effective in preventing hypoglycemia in healthy
adult horses

27. TREATMENT
Inotropic Agents, Vasopressors, and Local
Anesthetics
• Dobutamine (0.5–1 ìg/kg BW/min inadults
and 1–3 ìg/kg BW/min in neonates)is the
inotropic agent of choice in large animals,
• Dobutamine should be diluted in 0.9% NaCl,
5% dextrose,or lactated Ringer’s solution and
the dose carefully titrated by monitoring heart
rate and rhythm and blood pressure.

28. TREATMENT
Norepinephrine(0.01–1 μg/kg BW/min) is the
vasopressor agent of choice in hypotensive
animals that have not responded to
intravenous fluid loading or dobutamine.
Hyperimmune serum is commercially available
for the treatment of endotoxemia in the
horse.

29. TREATMENT
• Pentoxifylline is a methylxanthine derivative that
has been used in foals with septicemia because it
has been shown to suppress production of TNF-á
in a dose-dependent manner.
• Oral administration of pentoxifyllineat 10 mg/kg
BW produces serum concentrations similar to
those achieved at therapeutic levels in humans
when administered every 12 hours.
• Anticoagulants Heparin

30. Thank you