General Systemic States PDF

GENERAL SYSTEMIC STATES By Dr. Asmaa G. Saleh lecturer of Animal internal medicine Faculty of Veterinary Medicine Damanhur University  II- TOXEMIA AND ENDOTOXEMIA A clinical systemic state caused by wide spread activation of host de...

GENERAL SYSTEMIC STATES By Dr. Asmaa G. Saleh lecturer of Animal internal medicine Faculty of Veterinary Medicine Damanhur University  II- TOXEMIA AND ENDOTOXEMIA A clinical systemic state caused by wide spread activation of host defense mechanisms to the presence of toxins produced by bacteria or injury to tissue cells.  Presence of toxins circulated in the blood stream which either derived from bacteria or body cell metabolism.  Not all toxins cause toxemia, the bite of insects and snakes or ingestion of organic and inorganic poisons don’t cause toxemia.  Etiology (classification of toxins) I. Antigenic toxins (specific toxins)  They are toxins which produced by bacteria and to a less extent by helminthes (parasites).  These toxins act as antigens and stimulate antibodies production.  Antigenic toxins are divided into exotoxins and endotoxins (the most common form and the major cause of morbidity & mortality in farm animals.  Exotoxins Endotoxins  These are protein substances They are lipopolysaccharides found  very specific in their pharmacological in the outer wall of G-ve bac which effects present in the intestinal tract as a part  very specific in the antibodies that they induced of the normal microflora.  Produced by bacteria that diffuse Released into the immediate into the surrounding medium through surroundings when the bacteria cell wall ( secreted outside the undergo rapid proliferation or most bacterial cell) commonly when the bacterial cell wall breaks.  Example (Clostridium spp)  *Endotoxins are not absorbed through a. They may be ingested preformed as the intestinal mucosa if it is in cl. botulinum (botulism) damaged as in case of enteritis or acute b. or produced in large quantities by intestinal obstruction Endotoxins are heavy growth in the intestines, such absorbed systemic intoxication (endotoxemia) as in cl.perferingins type D (enterotoxemia) in sheep c. or from growth in tissue, as in cl. chauvei and  Example Gram-negative nauveii blackleg and black disease bacteria e.g. E. coli, Salmonella spp., Pasteurella spp.  Black disease a. discrete, irregular, pale infarcts on the liver surface, b. section through another affected liver shows a typical Blackleg in a large single infarct. carcase with extensive areas of darkened musculature.  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 entero- toxigenic E. coli , which causes a hypersecretory diarrhea in neonatal farm animals. Peracute entero-toxigenic E. coli diarrhea with voluminous Endotoxins may also be absorbed in the large amounts from sites other than intestine including mastitis, peritonitis, pneumonia, pleuritis, pericarditis, septic metritis, septicemia of neonates, myositis and meningoencephalitis. Mastitis in cow and goat septic myositis, severe swelling in the right thigh of bull, The most common causes of endotoxemia in horses are associated with diseases of the gastrointestinal tract including colitis, intestinal strangulation or volvulus and ileus complications associated with foaling and grain overload. a. A segment of foal jejunum and ileum strangulation, b. early intestinal volvulus.  II -Metabolic Toxins. They are toxins which produced and accumulated due to Incomplete elimination of toxic materials normally produced by Abnormal body metabolism metabolism.   Normally, toxic products produced in the alimentary tract or tissues excreted in the urine and feces or detoxified in the plasma and liver. When these normal mechanisms are disrupted (hepatic dysfunction) the toxins may accumulate beyond the critical point and the syndrome of toxemia appears.  *In liver diseases normal detoxification mechanisms : oxidation, reduction, acetylation and conjugation with glycine, glucuronic acid, sulfuric acid and cysteine are impaired, leading to toxemia In obstruction of the lower alimentary tract there may be increased absorption of toxic phenols, cresols and amines that are normally excreted with the feces resulting in the development of the syndrome of autointoxication.  The production of toxins by abnormal metabolism due to several disease condition give metabolic byproducts which harmful to body cell includes: Production of Ketosis (acetonemia) Lactic histamine & due to Acidemia histamine-like a abnormal due to substances fat increase in damaged Metabolism lactic acid tissues. caused Keton bodies by Acute ruminal acidosis  Endotoxins directly affects a large Pathogenesis number of cell types including mononuclear phagocytes, neutrophils, vascular epithelial cells, and platelets as primary targets. - These cells release a series of biochemical mediators which are responsible for many of the pathophysiological consequences of endotoxemia. - Endotoxins→ endothelial injury→ coagulation. - Endotoxins→ macrophage interleukins→ Key mediator of various inflammatory, Carbohydrate metabolism: ↓ blood sugar, ↓ liver glycogen and ↓ glucose tolerance of tissues………….. Protein metabolism: ↑ tissue breakdown→↑ blood NPN. Mineral metabolism: ↓Fe, Zn and ↑Cu, ceruloplasmin level in blood. Reproduction: Endotoxemia→ pregnancy failure and fetal death…. Effects on tissues and body systems: It affects endocrine glands and enzyme -Weakness of myocardium→ ↓ cardiac output +dilat. Of capillary wall→↓ blood pressure and circulatory failure Damage of liver and kidneys parenchyma→↑ blood NPN and albuminuria. - ↓ tone, motility of A.T→ ↓ appetite, digestion and constipation. - ↓ tone of skeletal muscles→ weakness. - Depression of function of nervous system→ dullness, depression end by coma. - Effects of specific toxins on N.S………… cl. tetani,  *Pathogenesis  Bacterial toxins circulate in the blood stream affect all tissues specially CNS…..dullness, depression, coma, death Bacterial endotoxins are potent pyrogens severe shock hemoconcentration due to movement of fluid from the vascular to extravascular space.  Also neutropenia due to leukocyte margination and sequestration Also hepatic dysfunction, hypoglycemia, abortion and alimentray stasis. *Carbohydrate metabolism Endotoxemia Hyperglycemia due to mobilization of hepatic glycogen Hypoglycemia due to decrease in liver glycogen and glucose tolerance of tissues  *Endotoxe mia Anerobic tissue metabolism Increase blood pyruvate and lactate levels  *Protein metabolism Endotoxe mia increase stimulation of tissue antibody breakdown production increase Increase total serum urea serum nitrogen protein( globulin and  *Trace elements Decrease Increased d Iron Copper (Hypoferremia) Zinc Ceruloplasm (Hypozincemia) in  *Nervous system Specific toxins of Cl- tetani and Cl-botulinum General depression Dullness Finally coma.  *Endotoxe mia Decreased liver function Damaged renal tubules and glomeruli Increased blood non- protein nitrogen Albuminuri a  *Endotoxe mia Myocardial weakness Loss of skeletal muscle tone Weakness and terminally by prostration  Clinical findings: A. Acute toxemia and endotoxemia 1. Anorexia, muscular weakness & depression. 2. Heart rates & intensity of the heart sound are increased which decreased later. 3. Pulse is weak & rapid (tachycardia) followed by decreased cardiac output. 4. Fever is common in the early stages but later the temperature may be normal or subnormal before death. 5. Cool skin and extremities. 6. Severe peripheral vasodilatation with a consequent fall in blood pressure. 7. Pallor of mucosa in some cases or congested. 8. Increased capillary refill time. Congested conjunctival Techinque of capillary mucous membrane. refill time.  Capillary Refill Time: Digital compression of the gingival mucosa escapes blood from the capillary circulation causing the mucosa to become pale. when compression is discontinued, the blood returns & the mucosa become pink again. The time taken for the return of color is known as the capillary refill time (CRT) & is used as an index of capillary perfusion. The normal CRT is 1-2 seconds. CRT is prolonged when capillary perfusion is low (e.g hypovolemic & endotoxic shock). 8. Muscular weakness, leading to recumbence. 9. Renal failure and is characterized by anuria. 10. Constipation. 11.Terminally, muscular weakness to the point of collapse and death occurs in a coma or with convulsion. 12. Calves not have a suck reflex, scant feces, but a low- volume diarrhea may also occur. B. Chronic toxemia Lethergy. Separation from the group. Inappetence. Failure to grow or produce.   Clinical pathology.low blood glucose. ▪ High blood NPN. ▪ High total serum protein (high globulin) in chronic toxemia. ▪ Albuminuria. ▪ Change in total and differential leukocytic count.  Differential Diagnosis toxemia Confused with Sub acute poisoning by arsenic and other metals which have a general depressing effect on most body enzyme systems Examination of the environment  Source of poison  Characteristic signs of each poison  Assays of food  Assays of gut contents and tissues *Clinical pathology of endotoxemia Acute endotoxemia characterized by: 1. Leukocytosis & neutrophilia in mild endotoxemia. 2. Leukopenia, neutropenia, lymphopenia secondary to the release of endogenous corticosteroids and redistribution of lymphocytes from peripheral blood and the spleen to lymphatic tissue with increasing severity and duration of endotoxemia. 3. Low plasma glucose concentration. 4. High serum urea concentration (NPN) )(azotemia). 5. Low serum albumin & total protein concentration. 6. Mild hypocalcemia, hypomagnesemia hypokalemia, hypophosphatemia, due to inappetence & decreased gastrointestinal tract motility More chronic toxemic states: High serum total protein concentration, with high globulins. Treatment: 1. Removal of infection foci. 2. Administration of broad spectrum antimicrobial drugs and antibiotic. Ampicillin and chloramphenicol , sulfamethazine or sulfonamides 3. Specific antitoxin (tetanus). 4. Excessive fluid and electrolyte therapy to combat the relative hypovolemia, hypoglycemia, electrolyte and acid-base disturbances. *Glucose and aa are added to the fluid to correct appetite and digestion. 5.Vitamin B complex may aid the enzyme utilization of glucose.  6. NSAIDs is injected because of their analgesic, anti- inflammatory and anti- pyretic effect. Flunixin meglumine , ketoprofen, ketorolac and phenylbutazone Flunixin meglumine is the NSAIDs commonly used in the treatment of endotoxemia in horses and cattle. Flunixin meglumine is a potent inhibitor of cyclooxygenase and its action on this enzyme to inhibit the synthesis of prostaglandin E2 may explain the anti-inflammatory action of the drug. 7. Glucocorticoids e.g. dexamethasone (1mg/kg BW i.v. every 24 hrs) are commonly used in acute endotoxemia.  improve capillary endothelial integrity and tissue perfusion.  decrease neutrophil aggregation,  stabilize lysosomal membranes, protect against hepatic injury  improve survival rate.  Toxemia in the recently calved cow Caused by several diseases in the period immediately after calving in the dairy cow; periparturient toxemia; acetonemia, fat cow syndrome, mastitis, peritonitis and septic metritis. The syndrome is characterized clinically by lack of appetite, marked reduction in milk yield, reduced ruminal and intestinal activity, dullness, lethargy and a fever. Recently diseased calved cow with signs of toxemia.  III. Septicemia &Viremia 1. Septicemia Septicemia is the acute invasion of the systemic circulation by pathogenic Mos and toxins accompanied by sepsis or septic shock with possible bacterial localization in various body systems or organs if the animal survives.(sudden deaths occur) Septicemia is a common cause of morbidity and mortality in newborn farm animals which have not received a sufficient quantity of colostrums in the first 24 hours after birth. In septicemia, the pathogen is present throughout the course of the disease and is directly responsible for initiation of the disease. Bacteremia is different from septicemia in that bacteremia is not accompanied by sepsis or septic shock. In bacteremia, bacteria are present in the blood stream for only transitory periods and do not produce clinical signs till secrete toxins and produce clear clinical signs (convert to septicemic disease). Etiology: Many different infectious agents can result in septicemia: Anthrax, pasteurellosis, salmonellosis in all species. Neonatal septicemias by Gram-negative bacteria. Bacteremia and septicemia in calves, lambs and foals are often associated with E. coli & Salmonella spp. Anthrax (splenic fever), with Severe cranioventral sudden death and enlarged, pneumonia. in calf caused dark, soft spleen. by P. multocida  Pathogenesis Two mechanisms are present in septicemia Mechanism Mechanism of of toxemia fever the exotoxins or endotoxins produced by the infectious agents initiate a profound toxemia and high fever because of their initiation of the release of host mediators and because of the rapidity with which the agents multiply and spread to all body tissues Disseminated intravascular Coagulation (DIC) Bacterial cell wall endotoxin Ag-Ab complex Circulating in blood stream Damage to tunica intema of blood vessels 1. Subsequent adherence of platelets and formation of platelets thrombi Hypercoagulation 2. Consuming of platelets and clotting factors Hypocoagulation Activation of fibrinolysis lead to hemorrhage Petechial hemorrage  The circulating M.OS with toxins and necrotic tissue make localization at Heart valves or B.Vs heart failure, rupture and sudden death. Joints arthritis Eye ulcer Brain meninges meningitis, coma and death Localized infection Clinical findings: The major clinical findings in septicemia are: 1. Fever, tachycardia, polypnea, hypotension and shock. 2. Submucosal, and subepidermal hemorrhages, that usually petechial or ecchymotic under conjunctiva & in the mucosa of the mouth and vulva. 3. Signs of myocardial asthenia and respiratory distress. 4. Specific signs as the result of localization of the infection in joints, heart valves, meninges, eyes or other organs. Clinical pathology: 1. Isolation of the causative bacteria from blood. 2. Leukopenia in viremia or leukocytosis in septicemia. 3. Low levels of serum total protein & immunoglobulins. Treatment: Similar to those described for the treatment of toxemia, fever 1. Parental broad-spectrum antimicrobial agents. 2. General supportive measures. 3. Source of immunoglobulins by plasma or blood transfusion is necessary for neonatal septicemia. In septicemic disease treatment not start with fluid therapy Use it after specific treatment by 4-5d As fluid therapy increase blood fluidity and hemorrhage NEONATAL SEPTICEMIA: Neonatal septicemia is common in all farm animal species from a few hours up to several days of age especially in colostrums deprived neonates. (pastrela, E.coli, salmonella Common clinical signs are:  Recumbency.  Depression.  Absence or marked depression of suck reflex.  Dehydration.  Fever. Neonatal calf with P.  Bloody diarrhea. multocida septicemia  Congested mucous membranes.  Weakness.  Weak pulse.  Omphalophlebitis. High death in neonatal  Polyarthritis. calves caused by a highly virulent S.  Rapid death. typhimurium strain  B. VIREMIA Viremia is the invasion of the systemic circulation by pathogenic viruses with localization in various body tissues and in which the lesions produced are characteristic of the specific virus e.g. malignant head catarrhl in cattle & African horse sickness in horse. Malignant head African horse sickness catarrh in cattle. in horse.  IV. Disturbances of free water, electrolytes and acid-base balance: A. Disturbances of free water 1. Dehydration 2. Acute overhydration (water intoxication) B. Electrolyte imbalances 1. Hyponatremia 2. Hypochloremia 3. Hypokalemia 4. Hyperkalemia 5. Hypocalcemia 6. Hypophosphatemia 7. Hypomagnesemia C. Acid-base imbalance 1. Acidemia 2. Alkalemia  A. DISTURBANCES OF FREE WATER 1. DEHYDRATION Dehydration mean a disturbance of body water balance in which More fluid is lost from the body than is absorbed Reduction in circulating volume of the blood, electrolytes imbalance & dehydration of tissues. Etiology: I. Inadequate water intake in case of: Prolonged thirst or starvation. Inability to drink water as in pharyngeal or esophageal obstruction or paralysis. Lack of thirst desire due to toxemia. II. Excessive loss of body fluid due to:  Gastro-intestinal disturbances: profuse watery diarrhea, acute intestinal obstruction, contineous profuse salivation and vomiting, prolonged use of purgatives, dilatation and torsion of abomasums and acute carbohydrate engorgements.  Urinary disturbances: polyuria as in diabetes mellitus & prolonged use of diuretic.  Skin disturbances: copious sweating, heat and sun stroke, excessive skin burns or wound and oozing of serum and hemorrhage during major operation.  Excessive accumulation of fluid in body cavities: as in ascites, peritonitis, pleurisy and hydrothorax.  Pathogenesis: Two factors are involved in the pathogenesis of dehydration: 1. Depression of tissues water content resulting interference in tissue metabolism. 2. Reduction in the free water content of blood Lead to Negative water balance  1. Initial response Withdrawal of intercellular and interstitial fluid to maintain of normal blood volume. Results in: loss of skin elasticity, dryness of the skin and mucosa, and a reduction and retraction of the eyeball due to reduction in the volume of the postorbital fat deposits.  2. Secondary response Reduction in the fluid content of the blood Results in: a reduction in circulating blood volume and an increase in the concentration of the blood (hemoconcentration).  3. Dehydration exerts important effects on tissue metabolism. Breakdown of fat, then carbohydrate and finally protein, to produce metabolic water and the formation of acid metabolites (fatty acids, lactate), glucose , a.a and the development of metabolic acidosis.  4. Urine formation decreases because of the restriction of renal blood flow. the increased endogenous metabolism a moderate increase in blood levels of NPN.  5. Dehydration may cause death especially In acute intestinal obstruction, vomiting and diarrhea. If combined with other systemic states, such as acidosis, electrolyte imbalances, toxemia and septicemia. Clinical findings: 1. Drying and wrinkling of the skin are the first and most important clinical findings in dehydration. 2. The eyes recede into the sockets (sunken eyeball). Sunken eyeball in the cows. 3. The skin (middle third of the neck, skin of upper eyelid) subsides slowly (loss of its elasticity) after being picked up into a fold (skin fold test). Skin fold test in a. cow, b. horse, c. cat. 4. Anorexia, muscular weakness, general emaciation and loss of body weight. Muscular weakness, emaciation, depression in a.cat, b. calf, c. cow. 5. Dryness of cornea, oral cavity and muzzle. 6. Constipation with hard feces and sluggish intestinal motility. 7. Oliguria, bradycardia, and decrease respiratory rates. 8. Subnormal temperature, coldness of body extremities, and recumbence in advanced cases before coma and death. Dead calf after recumbancy due to dehydration. Clinical pathology: Blood Increased packed cell volume (>40%) & plasma osmolarity. Serum Increase serum urea nitrogen (>35% mg), total serum protein concentration and imbalance of electrolytes. Feces Decrease moisture content. Urine Oliguria, increase in concentration and specific gravity. Percentage body weight losses in relation to some clinical signs, laboratory test and fluid requirement. Body Sunken Skin fold test PCV Total serum Fluid weight eyes & face persistence for % solids g/L requirement losses m1/kg B.W 4-6% Slightly < 2 sec. 40-45 70-80 20-25 6-8% ++ 2-4 Sec. 50 80-90 30-50 8-10% +++ 6-10 Sec. 55 90-100 50-80 10-12% ++++ 20-45 Sec. 60 120 80-120 Prognosis: Good  If the animal urinates  Young animal able to suck his mother  The state of the feces become toward the normal. Bad  If the body weight loss exceed 10-20%.  Presence of bacteremia, viremia, septicemia or presence toxemia.  Severe electrolyte imbalance and disorders of acid base balance. 2. ACUTE OVERHYDRATION (WATER INTOXICATION) Etiology: 1. The ingestion of excessive quantities of water when animals are very thirsty. 2. Calves, 2-4 months of age are most commonly affected but the disease is also recorded in adult cattle, sheep and goats.  pathogenesis Osmotic pressure of Na Normally luminal S.I is K RBCs isotonic to plasma Dehydration due to deprivation of water Water deprivation Na ions toxicosis hypernatremia Increase of osmotic pressure extracellular  Sudden rehydration within 5 minutes of water ingestion because thirsty calves close their esophageal groove when drinking. a large volume of water in the abomasum the duodenum. Rabid decrease in the osmolarity of small intestine content Free water rapidly moves from the small intestinal lumen into the circulation Hypo osmolarity of plasma Fluids continue to move Expansion and rupture  leading to  Intravascular hemolysis,  Hemoglobinemia & hemoglobinuria,  Hyponatremia & hypochloremia.  Decrease in plasma protein concentration. Cerebral odema Case fatality Low and hemoglobinuria persists for only a few hours. Clinical findings: 1. Hemoglobinuria (dark red urine) and signs of severe hemolytic anemia as a result of intravascular hemolysis. 2. Tachycardia and hypothermia 3. Affected animals are usually depressed and weak. Clinical pathology: Hemoglobinuria hemoglobinemia hypo osmolality hyponatremia  hypochloremia Treatment: Hypertonic saline (7.2% NaCl, 5 ml/kg BW over 5 min i.v. inj.) to correct the hyponatremia & hypochloremia. Treatment is not necessary in mild cases. Control: Water intoxication does not occur commonly and can be avoided by give the animal adequate water. Calves should have water by the end of the first week of life.