-Diyala University -Internal medicine
-College of Vet. Medicine - Lecture (5)
-Dep. Of Internal and Preventive Medicine
Dr. Khalid M. Hammadi
Toxemia is a clinical systemic state caused by widespread activation of host defense mechanisms to the presence of toxins produced by bacteria or injury to tissue cells. Toxemia does not include the diseases caused by toxic substances produced by plants or insects or ingested organic or inorganic poisons. Theoretically, a diagnosis of toxemia can be made only if toxins are demonstrable in the blood stream.
The most common form of toxemia in large animals is endotoxemia, caused by the presence of lipopolysaccharide cell wall components of Gram-negative bacteria in the blood,
The abnormalities of endotoxemia include : o Marked alterations in cardiopulmonary function o Abnormalities in the leukon (neutropenia and lymphopenia) and thrombocytopenia that may lead to coagulopathies. o Increased vascular permeability. o Decreased organ blood flow and metabolism, leading to heart and renal failure. o Decreased gastrointestinal motility e Decreased perfusion of peripheral tissues, leading to shock o The need for intensive and complex therapy o A high case fatality rate .
Gram-negative bacteria such as E. coli , Salmonella spp., Pasteurella spp. and
Histophilus somni, as examples.
- ETIOLOGY OF TOXEMIA AND ENDOTOXEMIA
Toxins can be classified as antigenic or metabolic .
Antigenic toxins
These are produced by bacteria and to a lesser extent by helminths. Both groups of pathogens act as antigens and stimulate the development of antibodies. Antigenic toxins are divided into exotoxins and endotoxins .
-Exotoxins
These are protein substances produced by bacteria that diffuse into the surrounding medium. They are specific in their pharmacological effects and

in the antibodies that they induce. The important bacterial exotoxins are those produced by Clostridium spp.
- Enterotoxins
These are exotoxins that exert their effect principally on the mucosa of the intestine, causing disturbances of fluid and electrolyte balance. The most typical example is the enterotoxin released by enterotoxigenic E. coli, which causes a hyper secretory diarrhea in neonatal farm animals .
- Endotoxins
The endotoxins of several species of Gram-negative bacteria are a major cause of morbidity and mortality in farm animals. The endotoxins are lipo­ polysaccharides found in the outer wall of the bacteria.
Metabolic toxins:-
These may accumulate as a result of incomplete elimination of toxic materials normally produced by body metabolism or by abnormal metabolism. Normally toxic products produced in the alimentary tract or tissues are excreted in the urine and feces or detoxified in the plasma and liver.
-PATHOGENESIS OF ENDOTOXEMIA
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 greater quantities of endotoxins escape the intestine when the mucosal barrier is disrupted by intestinal ischemia, trauma, ionizing radiation, bacterial overgrowth, reduced luminal pH or inflammatory intestinal disease These conditions not only temporarily over whelm the capacity of the liver to remove endotoxin from the portal circulation but also allow transmural movement of endotoxins into the peritoneal cavity from which they reach the peripheral blood Endotoxemia may also occur when Gram-negative bacteria gain access to tissues and/or blood. Most of these organisms liberate endotoxin during rapid growth An example is coliform septicemia in newborn farm animals. Once the endotoxins gain access to the blood ,they are removed from the circulation by the mononuclear phagocyte system , and the response of these phagocytes to the lipopolysaccharides determines the severity of the clinical illness.

- Cardiopulmonary function:
The hemodynamic effects of endotoxemia are manifested in two phases.
The first called is hyperdynamic phase of endotoxemia In which , 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. However, despite the absolute increase in cardiac output and oxygen delivery during this hyperdynamic phase, blood flow still may be inadequate to meet the needs of tissues in a hypermetabolic state During the hyperdynamic state, affected animals hyperventilate and have decreased capillary refill time and red, congested mucous membranes Ischemia of intestinal mucosa is manifested clinically by diarrhea may occur. Decreased renal perfusion will result in decreased urine output With uncontrolled endotoxemia, the hyperdynamic phase progresses to the : hypodynamic phase of shock. Changes include decreased cardiac output, systemic hypotension, increased peripheral resistance and decreased central venous return Hypothermia, rapid irregular pulses prolonged capillary refill time, pale to cyanotic mucous membranes, acidemia and hypoxemia provide clinical evidence of this advanced stage of endotoxemia The skin and extremities are cool. Sever pulmonary edema and increasing pulmonary hypertension occur.
Gastrointestinal function: ­
Endotoxemia can cause a profound inhibition of gastrointestinal motility , including the stomach, small and large intestine. Postoperative ileus is a frequent and serious complication of equine colic surgery and there is a good correlation between the incidence of ileus and the presence of ischemic intestine. Low doses of endotoxin infused into ponies produced profound disruption of normal fasting intestinal motility patterns, with an inhibition of gastric contraction amplitude and rate.
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. 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.
1-Severe peripheral vasodilatation with a consequent fall in blood pressure
2-Pallor of mucosa
3-Hypothermia
4-Tachycardia
5-Toxemia and endotoxemia
6- Pulse of small amplitude
7- Muscle weakness .
The clinical findings of severe endotoxemia include :
1- Depression
2- Hyperthermia followed by hypothermia
4- Decreased systemic blood pressure
5- Cool skin and extremities
6- Diarrhea
7- Congested mucosae with an increased capillary refill time
8- Muscular weakness, leading to recumbency
- Chronic toxemia:
Lethargy, separation from the group, inappetence, failure to grow or produce and emaciation are characteristic signs of chronic toxemia.
- CLINICAL PATHOLOGY OF ENDOTOXEMIA :
Changes in total and differential leukocyte numbers occur in endotoxemia .
Leukocytosis and neutrophilia occur with mild endotoxemia and leukopenia , neutropenia and lymphopenia increase in severity and duration with increasing severity of endotoxemia. Endotoxin induced rebound neutrophilia may occur and is attributed to an accelerated release of neutrophils from the bone marrow reserve into the circulation through generation of the neutrophil releasing factor.

A low plasma glucose concentration, high serum urea concentration non protein nitrogen), and a low serum albumin and total protein concentration are concentrations are in response to increased capillary permeability.
TREATMENT OF ENDOTOXEMIA:
The principles of treatment of endotoxemia or septic shock include: 1) removal of the foci of infection; 2) administration of antimicrobial agents with a Gramnegative spectrum; 3) aggressive fluid and electrolyte therapy to combat the relative hypovolemia, hypoglycemia, and electrolyte and acid-base disturbances; and 4) NSAIDs or glucocorticoids for the inhibition of products of the cyclooxygenase pathway. These four treat­ ments are routinely applied. Other treatments that may be applied in selected cases include the administration of intravenous or intramammary administration of polymyxin B, and hyperimmune plasma containing antibodies directed against core lipopolysaccharide antigens.
The intravenous infusion of large quantities of fluids and electrolytes is a high priority in the management of endotoxemia. Maintenance of peripheral perfusion is essential to any therapeutic regimen for treatment of endotoxic shock. Lactated Ringer's solution or other balanced electrolyte solution must be given by intravenous infusion over several hours. A beneficial response is noted by the following: o Correction of peripheral vasoconstriction o Restoration of an acceptable pulse quality o Return of urine output o Increase in the central venous pressure o Restoration of arterial blood pressure and Restoration of cardiac output o Restoration of oxygen delivery to acceptable levels.
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been in general use for the treatment of endotoxemia because of their analgesic, anti -inflammatory and antipyretic properties. NSAIDs suppress production of thromboxane and prostaglandins and reduce the acute hemodynamic response to endotoxemia
Although NSAIDs are routinely administered to endotoxemic animals. ,