Dr. Ghalib/ Internal Medicine lectures/ Systemic states/ Fourth year.
General systemic states
Toxemia
The presence of bacterial toxins or toxins produced by injury to tissue cells in blood stream causes toxemia but it does not include toxic substances produced by plants or insects or ingested organic and inorganic poisons. A common form of toxemia in farm animals is end toxemia caused by the release of endotoxins from gram negative bacteria causing abnormality of body systems. For example, bacteria such as E. coli, Salmonella spp, Pasteurella spp and Haemophilus spp. are responsible for many diseases of ruminants in which endotoxemia are common. These are mastitis, septic metritis, peritonitis, pneumonia, pleuritis, pericarditis and other. Endotoxemia is also one of the most common causes of death in horses affected with intestinal obstruction causing strangulation and ischemic necrosis. Etiology: Toxins could be either antigenic or metabolic. A-Antigenic toxins: Bacteria and some helminthes parasites produce antigenic toxins which stimulate the development of antibodies. These toxins are divided in to: 1) Exotoxin: Exotoxins are protein substances produced by certain bacteria particularly clostridium spp which exert their specific action and stimulates specific antibodies. These toxins may be ingested preformed as in cases of clostridium botulinum toxin or may be produced in large quantities by heavy growth of other clostridium spp causing enterotoxemia, or it may produce exotoxin in the tissue when clostridium grow there as in black leg and black diseases. Enterotoxin: Are exotoxins which act principally on the mucosa of intestine causing disturbances of fluid & electrolytes balance e.g. enterotoxins produced by ETEC causing diarrhea in neonates. 2) Endotoxins: Endotoxins are lipopolysaccharides found in outer wall of several spp of gram negative bacteria such as E. coli and salmonella spp. causing losses in farm animals. They are librated when the bacteria undergo rapid proliferation or when bacterial cell wall broken down. In severe local infection, endotoxin may gain access to blood e.g. coliform mastitis in dairy cattle. Endotoxins of gram negative bacteria in the intestine are not normally absorbed through intestinal mucosa unless it is injured as in cases of enteritis or acute intestinal obstruction resulted in absorption of large amount of endotoxins into
Systemic states.
1
Dr. Ghalib/ Internal Medicine lectures/ Systemic states/ Fourth year.
the circulation producing a state of toxemia. Endotoxin may also absorb from other sites including mammary glands, peritoneum, abscesses and septic foci. B- Metabolic toxins Toxic materials normally produced by normal metabolism in intestine or tissues are excreted in the urine, feces or detoxified in the plasma and liver. When these mechanisms are disrupted, as in liver dysfunction, the toxins may be accumulated and the syndrome of toxemia appears. In monogastric animals with obstruction of large intestine, the products of protein putrefaction such as toxic phenols, cresols and amines may be regurgitated into large intestine and absorbed into the blood rapidly when intestinal mucosal barriers is disrupted resulting in development of syndrome of autointoxication. Metabolic toxins may also produced by abnormal body metabolism including production of histamine and histamine-like substances in damaged tissues. Examples of toxemia caused by abnormal metabolism are: Ketones bodies in blood (ketonemia) due to faulty fat metabolism. Lactic acid in the blood (lactic acidemia) caused by acute grain overload. Pathogenesis: When endotoxin gains access to the blood, they are removed from the circulation by mononuclear phagocytes and the response of these phagocytes to the lipopolysaccharides determines the severity of clinical cases. The primary targets of endotoxins are phagocytes, neutrophils, epithelial cells of blood vessels and platelets. These cells release a series of biochemical mediators which include: o Cytokines o Platelet activating factors o Thromboxane A2 o Prostaglandins o Leukotrines o Proteinases and vasoactive amines. Macrophages become highly activated by endotoxin lipopolysaccharides. The cytokines derived from macrophages are responsible for many pathophysiological effects of endotoxemia caused by gram negative bacteria, these are: 1- Cardiopulmonary function: In the early stages, heart rates and cardiac output increase although blood pressure is almost normal. This is known as hyperdynamic phase of endotoxemia. During this phase, affected animals hyperventilate and have decreased capillary refill time, red congested mucous membranes, diarrhea and decreased urine output.
Systemic states.
2
Dr. Ghalib/ Internal Medicine lectures/ Systemic states/ Fourth year.
In advanced cases of endotoxemia, hyperdynamic phase progresses to the hypodynamic phase with signs of shock, hyperthermia, rapid irregular pulses, pale to cyanotic mucous membranes, cold skin & extremities, severe pulmonary edema and interstitial edema due to increase vascular permeability. Endotoxemia causes neutrophilia followed by severe neutropenia. Persistence of severe neutropenia is poor prognostic indicator. Hemoconcentration is due to movement of fluid from blood vessels to extracellular spaces. 2- Hemostatic system: Endothelial injury caused by endotoxin may expose subendothelial collagen and tissue thromboplastin initiating coagulation cascades. 3- Thermoregulation: Bacterial endotoxins stimulate macrophages interleukins 1 which induce fever and immature neutrophils, muscle proteolysis through increased prostaglandin E2 production. Fever is followed by hypothermia. 4- Carbohydrates metabolism. Endotoxins caused a fall in blood sugar level, disappearance of liver glycogen and decreased glucose tolerance of tissue so that administered glucose is not used rapidly. 5- Protein metabolism: In endotoxemia, there is an increase in tissue breakdown (catabolism) and rise in blood non-protein nitrogen (NPN). Inspite of tissue breakdown, there is an increase in total serum protein as result of antibodies production. 6- Reproduction: Endotoxemia cause pregnancy failure due to the effect on corpus luteum or decreased progesterone and fetal death. Endotoxin has a negative effect on the genital function of the ram because of changes of testosterone. 7-Effects on body systems: a- The myocardium is weakened, the stroke volume decreases. There is damage to capillary wall so the effective blood volume is decreased leading to fall in blood pressure and development of circulatory failure. b- There is decrease of liver function and damage to renal tubules and glomeruli cause rise in blood non-protein nitrogen and albuminuria. c- Alimentary dysfunction includes impaired digestion, constipation and loss of appetite. d-Endotoxin may affect nervous system with signs of dullness and depression and finally coma. 8- Hypersensitivity:
Systemic states.
3
Dr. Ghalib/ Internal Medicine lectures/ Systemic states/ Fourth year.
Some endotoxins may cause hypersensitivity at the first infection so second infection by the same bacterial antigen may cause anaphylaxis or allergic cases such as purpura hemorrhagica. Clinical findings: 1) The common clinical signs of acute toxemia are depression, anorexia and muscular weakness. While the characteristic signs of chronic toxemia include those of lethargy, separation from the group, inappetence, failure to grow & emaciation. Constipation is usual; pulse is weak, rapid & regular. There may be albuminuria. The heart rate is increased and initially, the intensity of the heart sounds is increased but later as toxemia worsens the intensity may decrease. Fever is common in the early stages of endotoxemia but later the temperature may be normal or subnormal. Terminally there is muscular weakness to the point of collapse and death occurs in coma or with convulsions. Diagnosis: 1- Non-specific endotoxin may be assayed in the blood by biological technique. 2- Hematological examination shows a- Low blood glucose, high blood non-protein nitrogen, high total serum protein, particularly globulins and albuminuria. b- Changes in total and differential leukocytic count e.g. leucopenia, neutropenia increase in severity of endotoxemia. Leukocytosis and neutrophilia may occur with mild endotoxemia. 3- Isolation and identification of specific exotoxin may be possible. Treatment: The principles of treatment of endotoxemia and septic shock may include: 1- Removal of infection foci and 2- Administration of antimicrobial, broad spectrum antibiotic will usually control the infection and the animal will recover. 3- Expansion of intravascular volume and support cardiovascular function by administration of large quantities of fluid & electrolytes. Large volumes of isotonic solution have been standard practice. Lactated ringer’s solution or a balanced electrolyte mixture must be given IV infusion over several hours. Glucose should be included in the fluid & electrolyte solutions. 4- Prevention of action of shock mediators using glucocorticoids to improve cellular metabolism and gluconeogenesis. The corticoids commonly used in endotoxic shock are
Systemic states.
4
Dr. Ghalib/ Internal Medicine lectures/ Systemic states/ Fourth year.
a- Hydrocortisone b- Prednisolone c- Methylprednisolone and d- Dexamethazone. They are used most commonly in acute cases and in a dose such as 1 mg/kg b.w. of dexamethazone IV every 24 hours. 5- Non-steroidal anti-inflammatory drugs (NSAID) such as acetyl salicylic acid and phenylbutazone are also used. Similar drugs have been used recently such as: a- Indomethacin b- Sodium meclofenamate and flunixin meglumine
Septicemia
It is a state in which viruses, bacteria or protozoa are present in large numbers in the blood accompanied with toxemia and hyperthermia. Etiology: Diseases associated with septicemia include: Anthrax Salmonellosis Pasteurellosis Rift vally fever Neonatal septicemia such as E. coli septicemia, Listeria monocytogenes and Salmonella. - The difference between bacteremia and septicemia that in bacteremia, the bacteria are present in the blood for only transitory periods and do not produce clinical signs. - Special septicemia such as radiation septicemia resulting from loss of RBCs production because of injury to bone marrow. - Congenital defects in immune system, immunodepression as result of corticosteroid therapy or toxins such as bracken or viral infection such as bovine virus diarrhea (BVD) may result in septicemia. Pathogenesis: - The exotoxins or endotoxins cause profound toxemia and high fever because of the rapid multiplication of microorganism and spread of the toxins to all body tissue. Localization in many organs may occur causing serious defects in animals survive the toxemia. Toxins also cause direct endothelial damage and hemorrhage into tissue commonly result.
Systemic states.
5
Dr. Ghalib/ Internal Medicine lectures/ Systemic states/ Fourth year.
-Toxins are not produced by viruses so that general signs which occur due to viremia are caused by the products of the tissue cells killed by the multiplying virus. Clinical findings: There are signs of toxemia, fever, hemorrhages usually petechial or ecchymotic which are best seen subconjunctival and in the mucosa of the mouth and vulva. Localization of infection in joints, heart valves, meningies, eyes or other organs results in localizing signs. Diagnosis: 1- Positive diagnosis of septicemia can be made by isolation of the causative agent from blood samples. 2- The presence of petechiae in mucosa and conjunctiva may suggest septicemia. 3- Localizing signs in certain organs may have a contributory evidence that septicemia is present. Treatment: a) In septicemia urgent treatment with IV or intraperitoneal injection of antibacterial drugs or sera and antitoxin should be provided as soon as possible. b) Avoid spread of diseases by strict hygienic precautions.
Fever
It is a syndrome in which hyperthermia and toxemia are produced by substances circulating in the blood.
Etiology: 1- Septic fever is caused by bacteria, viruses, protozoa or fungi either in form of localized infection as abscess or systemic infection as bactermia or septicemia. 2- Aseptic fever such as chemical fever which occur due to injury of foreign protein or surgical fever due to breakdown of tissue or blood. A- Aseptic fever may be due to tissue necrosis as in cases of: a) Severe intravascular hemolysis. b) Extensive infarction. c) Breakdown of muscle after injection of necrotizing materials. d) Extensive necrosis in rapidly growing tumors.
Systemic states. 6
Dr. Ghalib/ Internal Medicine lectures/ Systemic states/ Fourth year.
B- Aseptic fever also results from immune reactions e.g. Anaphylaxis, angioneurotic edema. Pathogenesis: The febrile response is initiated by the introduction of exogenous pyrogens to the body. These include pathogens such as bacteria, viruses, bacterial endotoxins (lipopolysaccharides), antigen-antibody complexes, hemoglobinuria and many inorganic substances. In response to these exogenous pyrogens, the body produces endogenous pyrogens (leukocytic pyrogens) which are released from certain leukocytes, the best known of these leukocytic pyrogens is interleukin 1 produced by monocytes and macrophages which mediate most fevers by inducing an abrupt increase in the synthesis of prostaglandins (particularly PGE2) in the anterior hypothalamus which control the thermoregulatory mechanism in the body so that the thermostatic level of the body is raised by increased heat production and prevention of head loss. Clinical findings: There is elevation of body temperature. An increase in pulse rate, hyperpnea, wasting, oliguria often with albuminura, increased thirst, anorexia, constipation, depression and muscle weakness. The temperature is always moderate and rarely goes above 42 C. Diagnosis: a) There are no clinicopathological findings characteristics of fever. b) Laboratory findings will reflect the changes associated with the cause of fever. c) Differentiation from hyperthermia is associated with physical abnormalities. It could be differentiated from septicemia which accompanied by infection of the blood. Treatment: 1. Antibacterial drugs are necessary to remove the toxin and control infection. Specific antibodies (sera) and antitoxins may be used to control the infection and reduce the effects of bacterial toxins. 2. Removal of necrotic in aseptic fever. 3. Non-specific trt include the use of glucocorticoids to facilitate repair process and alleviate inflammation. 4. NSAID, the antiprostaglandins including salicylates and phenylbutazone may be used. 5. Fluid and electrolytes therapy should be given.
Systemic states.
7
Dr. Ghalib/ Internal Medicine lectures/ Systemic states/ Fourth year.
6. If the fever is high, antipyretics such as salicylates, dipyrone, acetaminophen and flunixin meglumine which inhibit prostaglandin synthesis acting centrally to lower the thermoregulatory set point.
Hyperthermia (Heat stroke)
It is an increase in body temperature due to failure of heat loss or due to heat production or absorption when the causes of abnormalities are purely physical. Etiology a) The physical abnormalities include high environmental temperature, prolonged severe muscular exertion in humid areas when the animal are fat and have a heavy hair coat and animal are confined with inadequate ventilation. There is a difference between breeds of animals in their tolerance environmental high temperature, exposure to sunlight and exercise e.g. water buffalo are less heat tolerant than other animals. b) Hyperthermia may occur due to other causes such as: i. Dehydration may occur due to insufficient tissue fluid. ii. Excessive muscular activity e.g. strychnine poisoning. iii. Administration of tranquilizing drugs to sheep in hot weather. iv. Poisoning with specific mycotoxins in cattle. v. Iodism. Pathogenesis: a) Hyperthermia of short period has an advantage in infectious diseases because phagocytosis and immune body production are facilitated and most invading microorganism viability is impaired. However, in hyperthermia the metabolic rate increased up to 40-50%, liver glycogen stored are depleted and extra energy is derived from increased endogenous protein metabolism. b) Anorexia may occur, dryness of the mouth and increase thirst, loss of body weight and lack of muscle strength accompanied with hypoglycemia and rise in NPN. c) An increase in heart rate occurs due to rise of blood temperature and a fall of blood pressure resulting from peripheral vasodilatation. d) Respiratory rate and depth may increase due to rise of body temperature. e) Urine output is also decreased because of the reduced renal blood flow resulting from peripheral vasodilatation.
Systemic states.
8
Dr. Ghalib/ Internal Medicine lectures/ Systemic states/ Fourth year.
f) When temperature exceeds a critical point, there is depression of nervous system activity; depression of respiratory center usually causes death by respiratory failure. g) Myocardial weakness with rapid irregular heart rate may result in circulatory failure. Clinical findings: A. Hyperthermia occurs when the rectal temperature exceeds 39.5 C and may reach 43.5 C. in most instances the temperature exceeds 42 C. B. In the early stages, there is increased thirst and the animal seeks cool places, lying in water. When temperature reaches 41 C respiration is labored and when temperature raises more the respiration become shallow and irregular, the pulse become very rapid and weak. These signs are usually accompanied by collapse, convulsion and terminal coma. C. Death occurs in most species when temperature is 41.5-42.5 C. abortion may occur with high embryonic death when hyperthermia prolonged. Diagnosis: 1-It should be differentiated from fever and septicemia. It is not easy to differentiate it from fever, although in fever the temperature seldom exceeds 42 C. but in septicemia petechial hemorrhages in the mucosa and skin may be present beside blood culture may be positive in bacterial infections. 2-Examination of environment may reveal the causative factor. Treatment: When hyperthermia is severe and for long duration, treatment is necessary by the following methods: A- IV injection of normal saline or 5% dextrose. Cold applications including spraying, immersion, rectal enema or cold packs are also effective. B- Supportive treatment includes providing adequate glucose and protein. C- Adequate drinking water is essential with shed and air movement when animal exposed to high air temperature. D- If the animals have to be confined under conditions of high temperature and humidity, the use of tranquilizing drugs has been recommended to reduce unnecessary activity.
It Hypothermia
Systemic states.
9
Dr. Ghalib/ Internal Medicine lectures/ Systemic states/ Fourth year.
occurs due to excessive heat loss or decrease heat production so the body temperature falls. Etiology: a- Exposure to cold air, decreased muscle tone as in milk fever and acute ruminal impaction. b- During anesthesia and sedation. c- Peripheral vasodilatation in shock. d- Reduction of metabolic activity in terminal stages of many diseases are common cause of hypothermia in which a sudden fall in temperature (premortal fall) is a bad prognosis sign. Clinical findings: 1) It affects newly born animals mainly exposed to cold windy weather. The resulting hypothermia cause mortality among these animals when there is wetness and starvation. 2) The animals may show weakness, depression and recumbency. 3) Respiratory and heart rates are slow and consciousness is lost.
Diagnosis: Body temperature, environmental temperature, clinical signs and history of parturition during windy cold weather may be of value in diagnosis. Treatment: A- Adequate supply of rich energy diet. B- Providing a warm shelter from cold. C- Newborn animals should be dried off and given colostrums by stomach tube (50 ml/kg) D- Lambs with severe hypothermia should be given intraperitoneal injection of 20% glucose at temperature of 39 C (25-50 ml).
Stress
It is any stimulus, internal or external, chemical or physical or emotional that excites neurons of the hypothalamus to release more corticotrophin-releasing hormone than normal at rates than that in absence of stimulus. It is a systemic state which develops as result of the long term application of stressors. Stressors are environmental factors which stimulate excessive physiological, haemostatic and behavioral responses.
Systemic states.
10
Dr. Ghalib/ Internal Medicine lectures/ Systemic states/ Fourth year.
Etiology: It may occur due to 1) Prolonged periods of road transportation particularly during inclement weather and over crowding, are the major stresses associated with an increased incidence of infectious diseases. 2) A sudden change of climate specially temperature either as excessive heat or cold. 3) Excessive physical efforts as in fever, excitement and struggling in restrained animals. 4) Pain due to colic, dehorning and castration. 5) Crowding causing abnormal behavior 6) Nutritional causes as lack of food and water. 7) Harassment by man and other animals causing fear and elicit stress in animals is one of a significant causes of stress-related disease in animals. 8) Separation of animal from the herd or flock. Pathogenesis: A. Stress is concerning of adaptation of animals body to the environment so change of water may place a great strain on adaptation and are classified as stressors. B. The body system which affected by stress for long term response is endocrine system and nervous system for sensory inputs and short term response. C. Endocrine responses are principally adrenal medullary response related to situation which require immediate response and adrenal cortical response which operate if stressful situation persists. D. The response of farm animals to stressors particularly handling and road transportation may be in the form of increase blood concentration of cortisol, catecholamine, hematocrit, lipid and glucose. Diagnosis: 1) Direct stress assessment is the measurement of ACTH and indirectly of cortisol. Less direct assessment is that of plasma fibrinogen. 2) Field observations support the view that stress reduces resistance to infection. 3) Certain metabolic diseases maybe affected by environmental stress such as: a- hypocalcaemia in sheep and hypomagnesemia of cattle in cold weather. b- Acetonemia and pregnancy toxemia of cattle and sheep on deficient diets. c- White muscle disease of calves and lambs on vigorous exercise.
Systemic states.
11
Dr. Ghalib/ Internal Medicine lectures/ Systemic states/ Fourth year.
4) These diseases do have environment origins, but they can be prevented and cured without any intervention in the factor causing the stress. 5) Stress also affect on economic performance such as milk production, fertility and mastitis. 6) Metabolic stresses such as late pregnancy and early lactation makes the animals more sensitive to environmental stressors.
Sudden death
It means that animal is found dead without observing any signs of illness before death. - Diagnosis of the cause of the disease is often difficult because of absence of clinical signs and epidemiology although post mortem can be done. - It is necessary to distinguish between animal found dead and sudden death. - It is possible that sick animals are not observed frequently for a week interval for example or sick animal with signs of disease is not observed before death because the animals are run with large animal groups so sick individual animals are not closely observed to be ill and may die and considered to be a case of sudden death. Sudden death in single animals 1- Peracute endogenous toxemia. It occur due to a) Rupture of stomach of horses. b) Rupture of abomasum of cows. c) Rupture of colon in mares at foaling. In all of these cases, large amount of stomach and intestinal contents are deposited in the peritoneal cavity. 2- Peracute exogenous toxemia: it could be due to a snake bite. 3- Spontaneous internal hemorrhage: it could be due to a) Verminous mesenteric arteritis in horses. b) Rupture of aorta or atrium. c) Cardiac tamponade in cows. e. g. It was reported that 68% of horses with sudden death were undiagnosed and it was assumed that they died of exercise-induced acute heart failure. 4- Trauma may cause sudden death due fighting or falling or due to jumping obstacle causing either internal hemorrhage or damage to brain or medulla oblongata (atlanto-occipital joint trauma). 5- Iatrogenic deaths as in: a) Overdosing of calcium injected IV to an excited cow. b) IV injection of procaine penicillin suspension. c) IV injection of ivermectin in horses. d) Too rapid fluid infusion in an animal with pulmonary edema.
Systemic states. 12
Dr. Ghalib/ Internal Medicine lectures/ Systemic states/ Fourth year.
e) IV injection of crystalline penicillin causes sudden death in horses within one minute due to anaphylaxis reaction. Sudden death in a group of animals A- Diseases caused by infectious diseases causing toxemia or septicemia such as: Blackleg Anthrax Hemorrhagic septicemia Preacute pasteurellosis especially in sheep but occasionally in cattle. Clostridium perifringens enterotoxaemia in sheep & young cow. Grain overload in feedlot cattle. Colitis is about only cause of death in group of horses. B- Poisoning and nutritional the deficiency: Animals at pasture may die suddenly due to cyanide or nitrate poisoning. Acute myocardiopathy and heart failure may be caused by certain pasture or grass plants. Sudden death may come from sudden exposure of cattle to plants which cause bloat or hypomagnesemic tetany. It may occur because of drinking water from lakes and ponds with heavy growth of certain algae. C- Acute myocardiopathy in young animals on diets deficient in vitamin E or selenium also caused sudden death in this age group. D- In adult cattle deficient of copper may cause a falling diseases due to acute myocardiopathy. E- Monensin mixed with feed for cattle or horses does cause death by heart failure. Organophosphates also cause sudden death with apparent clinical signs. Soluble lead salts can cause quick death in young animals. F- Lightning strike or electrocution. It cause death in a group animals the history and examination of the environment reveals the cause. G- Neonatal and young animals, because of poor immune status, septicemia or toxemia cause by particular pathogens (E. coli) and hypothyroidism are important causes of sudden death. Examination of a sudden death incident: 1- For purpose of insurance inquiry or litigation good reports should be kept. 2- Careful history taking including feed change, it source exposure to poisons or administration of toxic materials. 3- Careful examination of environment and source of pathogen. 4- Careful examination of animals for signs of struggling, frothy nasal discharge, unclotted blood from natural orifices, bloat, pallor of mucosa, burn marks on the body. 5- P.M. examination by specialist should be performed. 6- Samples of suspected materials should be collected.
Systemic states.
13
Dr. Ghalib/ Internal Medicine lectures/ Systemic states/ Fourth year.
Shock It is a state in which there is acute serious reduction in tissue perfusion and is characterized by severe reduction in the effective circulatory blood volume and a severe reduction in systemic arterial blood pressure. Etiology: 1- Hypovolumic shock: It occurs as results of severe reduction in circulating fluid or blood volume as in: a- Severe hemorrhage with loss of 35% or more of total blood volume b- Dehydration from severe diarrhea or intestinal obstruction. 2- Cardiogenic shock: It results from acute reduction of cardiac output due to either. a- Acute myocardial damage or cardiac asthenia with loss of muscular power or b- Cardiac arrhythmia with loss of coordinated contraction. 3- Vasogenic shock (Distributive shock): It occurs due to vascular abnormalities as in. a- Cases of severe trauma or burns. b- Severe pain as in colic in horses. c- Uterine prolepses d- Extensive surgery and rapid withdrawal of fluid from body cavity (e.g. ascites) causes sudden reduction of the cavity pressure. 4- Toxic or septic shock: when endotoxins or other toxins or microorganism gain access to blood circulation acting on vascular system, septic shock occurs. e. g. 1- Endotoxemia caused by gram negative bacteria cause septic Shock. e. g. 2- Grain engorgement in cattle and horse - Infarction of large segments of intestine in horses. - Acute intestinal accidents cause absorption of toxins from the intestine with subsequent toxic shock. e. g. 3- Absorption of toxins of gram negative bacteria such as E. coli. from local infections such as mammary gland in coliform mastitis and the peritoneal cavity in acute diffuse peritonitis Pathogenesis: - In all forms of shock, there is marked reduction in effective blood volume with lowered cardiac output, hypotension and impaired tissue perfusion.
Systemic states.
14
Dr. Ghalib/ Internal Medicine lectures/ Systemic states/ Fourth year.
- A compensatory mechanism include the release of catecholamines which act to maintain perfusion through vital organs as brain and heart and by reducing blood flow to other tissues which further increase the degree of tissue anoxia. - Hypoxia and uncontrolled sepsis causes increase in vascular permeability allows the movement of albumin and fluid from blood vessels to the interstitial tissues resulting in hypovolemia. - In early stages of shock, it could be reversed by transfusion of fluid to restore the effective blood volume but later, the loss of cellular integrity in all tissues and development of disseminated intravascular coagulation (DIC) may cause irreversible lesion and shock. Clinical findings: 1- There is coldness of the skin, subnormal temperature. 2- Rapid shallow respiration and rapid heart rate accompanied weak pulse and lower pressure. Venous pressure is greatly reduced and veins are difficult to raise. 3- The mucosa is pale and in cases of hemorrhage, severe degree of blanching is observed. 4- The animal is weak, dull often recumbent and may die in coma if the condition is fatal. Diagnosis: - Tests used for diagnosis of shock are depending on the cause of shock. It may involve bacterial culture from sites of infection, total and differential leukocytic count, PCV, total protein estimations and blood lactic levels. - Tests for estimation of myocardial damage and of renal function. - Shock should be anticipated in: Septicemic diseases in neonate Acute localized infections. Intestinal diseases particularly in horses with acute intestinal obstruction. Severe trauma Severe fluid loss for any reason. Practice of fluid decompression (removal of fluid from body cavity) Significant surgical operation Peripheral circulatory failure is present without evidence of hemorrhage or dehydration. Treatment: - It is important to maintain tissue perfusion with aggressive fluid therapy also elimination of the primary causes of shock is also important.
Systemic states.
15
Dr. Ghalib/ Internal Medicine lectures/ Systemic states/ Fourth year.
- Shock cases need to be corrected surgically should be started early because delaying surgery until shock is advanced is mostly end fatally.
1- Antibiotic therapy: For treatment of shock which occur due to infection, broad spectrum bactericidal antibiotics should be used. The requirement for antibiotic therapy varies with the cause. It may be successful in cases such as gram negative septicemia in calves or foals or acute diffuse peritonitis and it is less successful in cases such as coliform mastitis. 2- Fluid therapy: Fluid therapy is most important therapy in cases of shock, these are: a- Crystalloid solutions which are fluids of balanced electrolytes such as lactated Ringer s solution which preferred to normal saline (0.9% NaCl) solution. These isotonic solutions are not expensive and are most commonly used in large animals. Large volumes of isotonic crystalloid solutions are required in the treatment of shock. An initial dose is of 50-1oo ml/ kg. b.w. by rapid IV. More fluids are administered as required on the basis of clinical response. Disadvantage of these solutions are the large volume required for treatment and repeated trt and the risk of development of pulmonary edema. In calves and ruminants, adequate tissue perfusion could be sustained by oral administration of large volumes of solutions orally. b- Colloid solutions, such as dextran, gelatin polymers, hexastarch could be administered IV in smaller volumes to expand plasma volume. Colloid solutions may have also a risk of induction of Pulmonary edema also increase risk for coagulopathy. Small volumes of hypertonic saline solution (7.2%) may be used in a dose of 3-5 ml/ kg. b.w. for treatment of hemorrhagic shock. It is suggested to be an alternative method for treatment of septic shock. 3- Corticosteroids: Although it is of little value in trt of shock once clinical signs developed, it has been used for trt with higher doses of 5-10 mg/ kg. b.w. of dexamethazone IV. Immunotherapy with antibodies acting against gram negative bacteria may be of value in therapy or prevention of endotoxic shock in some diseases. Vaccination using gram negative bacteria has proven to reduce the diseases and endotoxin-induced shock.
Systemic states. 16
Dr. Ghalib/ Internal Medicine lectures/ Systemic states/ Fourth year.
Disturbances of body fluids, electrolytes and acid-base balance Dehydration It means a loss of body water. A disturbance of body water balance in which more fluid is lost from the body than is absorbed results in reduction in circulating blood volume and in dehydration. Two major causes of dehydration are there, it is either due to A- lack of fluid intake, as in cases of: a- Deprivation of water b- Lack of thirst due to toxemia c- Inability to drink as in cases of esophageal obstruction. B- Excessive fluid loss due to: a- Cases of diarrhea which is the most common cause. b- Vomiting c- Polyuria d- Extensive skin wound e- Copious sweating. Dehydration also occurs in cases of: - Acute carbohydrates engorgement in ruminants - Acute intestinal obstruction - Acute diffuse peritonitis. Pathogenesis: It may involve two factors 1- Reduction of levels of tissue fluid resulting in interfering with tissue metabolism. 2- Reduction of blood fluid contents (anhydremia). A- The initial response to dehydration is the: a- Withdrawal of fluid mainly from the connective tissues, muscle and skin resulting in loss of skin elasticity, dryness of the skin and mucosa and sunken eye. Initial response also include b- The maintenance of normal blood volume B- The second response is a reduction in the fluid content of the blood causing a- Increase in concentration of the blood (hemoconcentration) with subsequent increase in viscosity of blood which impedes blood flow exacerbating the peripheral circulatory failure (PCF) b- Reduction in circulating blood volume (oligemia).
Systemic states.
17
Dr. Ghalib/ Internal Medicine lectures/ Systemic states/ Fourth year.
- Dehydration due to lack of fluid intake is minimal because kidneys compensates by decrease urine output and increase its concentration. While dehydration due to excessive fluid loss, as in cases of calf diarrhea, kidney compensate more effectively and oral fluid electrolytes intake is necessary to maintain plasma volume. - Some important effects of dehydration on tissue metabolism: 1- An increase in breakdown of fat the carbohydrates and finally protein to produce water of metabolism. 2- The increase of endogenous metabolism under anaerobic condition results in the development of acidosis. 3- Urine output decreases together with the increase endogenous metabolism cause moderate increase in non-protein nitrogen (NPN) 4- Dehydration hyperthermia with slight increase in temperature initially due to insufficient or poor sweating. 5- Death due to dehydration may occur but it is mainly due to combined effect with acidosis, electrolyte imbalance, toxemia and septicemia. Clinical findings: 1) Dryness and wrinkling of the skin, giving the body and face a shrunken appearance, is the first and most important sign. 2) Sunken eyes (the eye ball recede in the socket). 3) Skin tenting test may be performed on the skin of upper eyelid and of the neck by picking up the skin into a fold and record the time in seconds of the skin fold to subside. This test is one of the best indicators of the degree of dehydration and is commonly assessed as percentage of body weight loss as following: 6-8% dehydration when skin fold remain elevated for 2-4 seconds. 8-10% = = = = 6-10 seconds 10-12% = = = = 20-45 seconds 4) Loss of body weight occurs rapidly, there is muscular weakness and lack of appetite. 5) In simple dehydration due to water deprivation, dehydrated animals are very thirsty. In dehydration secondary to enteritis with severe toxemia, acidosis and electrolyte imbalance, there may be no desire to drink.
Electrolyte imbalance
Systemic states.
18
Dr. Ghalib/ Internal Medicine lectures/ Systemic states/ Fourth year.
Sodium, potassium, chloride and bicarbonates are the main electrolytes being lost in diseases of digestive tract. Cases of minor importance in farm animals accompanied by electrolyte losses are: Sweating particularly in horses Exudation from burns Excessive salivation and Vomiting Hyponatremia: Sodium ions are mostly found in the extracellular space. Hyponatremia is often associated with conditions that cause sodium depletion such as vomiting, adrenal insufficiency and acute diarrhea in calves with ETEC infection and in horses with acute diarrhea causing hypotonic dehydration A- Hypotonic dehydration occurs when the losses of exchangeable cations (sodium and potassium) exceed the net change water balance causing severe dehydration and severe hyponatremia. B- Isotonic dehydration occurs with balanced loss of water and electrolytes (Na & K) as in cases of simple enteritis, heavily sweating and nephrosis. This type of dehydration is mild plus hyponatremia. C- Hypertonic dehydration occurs when water losses exceed the loss of Na and K and is indicated by hypernatremia. Simple deprivation of water is an example of this type of mild dehydration. Hyponatremia can become more severe when sodium free water or 5% dextrose are used as the only fluid therapy in animals with dehydration accompanied with hyponatremia. This occur because an increase in the renal excretion of water to maintain normal osmotic pressure leading to decrease of circulatory blood volume, hypotension, PCV and renal failure. In hyponatremia, there is muscular weakness, hypothermia, dehydration and mental depression. Polyuria and polydipsia occur in cattle with dietary sodium chloride deficiency. Hypochloremia Normally a large amount of hydrochloric acid is secreted in the abomasums and chloride, potassium, and hydrogen ions of gastric juice are normally absorbed by the small intestine so in cases of intestinal obstruction, impaction and torsion of the abomasums, hypochloremia occurs as result of abomasal emptying and intestinal obstruction with subsequent sequestration of chloride, potassium and hydrogen ions leading to hypochoremic hypokalemic alkalosis. Hypokalemia It occurs due to:
Systemic states.
19
Dr. Ghalib/ Internal Medicine lectures/ Systemic states/ Fourth year.
1- Reduced dietary intake caused by anorexia 2- Excessive renal loss which may result from mineralcorticoid excess and certain diuretics. 3- In cases of abomasal stasis, intestinal obstruction and enteritis. Rapid administration of sodium bicarbonate can produce alkalosis with rapidly developing hypokalemia, because alkalosis may results of exchange of potassium for hydrogen ions in renal tubular fluid resulting in hypokalemia. For treatment of hypokalemic alkalosis, saline infusions are usually sufficient. Only in severe hypokalemia, solutions containing potassium are necessary. Hyperkalemia It is not common in farm animals as is hypokalemia. It occurs most commonly following severe metabolic acidosis. Potassium ions move from intracellular space to extracellular because the excess hydrogen ions are buffered intracellularly. Hyperkalemia may result from renal retention of potassium as in Addison s disease and acute renal failure. It may follow hemolysis and in stored whole blood. Hyperkalemia is more dangerous than hypokalemiabecause of its severe cardiotoxic effects. There is bradycardia, arrhythmia and sudden cardiac arrest may occur. Signs in horses include muscular weakness, tremors, reluctant to move, sweating and recumbency. Treatment consists of sodium bicarbonate or 5% dextrose. Acid-base imbalance The normal range of blood pH is of 7.35-7.45. The pH is maintained by buffering systems, the bicarbonate ions (the most important) and the dissolved carbon dioxide. These components of buffer system are proportionally maintained at constant level either by: a- Increased pulmonary ventilation and discharge of CO2 or b- By increased urinary excretion of bicarbonate radicals (HCO3). Acidosis Metabolic acidosis is characterized by decrease in arterial pH and bicarbonate concentration. Acidosis may be produced by addition of hydrogen ions or the loss of bicarbonate ions. The most common causes include: 1- Carbohydrate engorgement in ruminants and horses (lactic acidosis). 2- Ketosis in cattle and pregnancy toxemia in ewes (ketoacidosis). 3- Oral diseases causing hypersalivation (saliva rich bicarbonate).
Systemic states.
20
Dr. Ghalib/ Internal Medicine lectures/ Systemic states/ Fourth year.
4- Acute diarrhea in newborn animals and cases of acute enteritis in adult cattle and horses. 5- Diseases causing retention of CO2 in the blood due to interference with normal respiratory exchange such as pneumonia, severe pulmonary emphysema, congestive heart failure, depression of respiratory center, may all accompanied by acidosis. 6- Renal insufficiency or renal failure also contributes to acidosis by decrease in renal excretion of acid. 7- Administration of excessive quantities of acidifying solutions for treatment of alkalosis may cause acidosis. Pathogenesis: In response to metabolic acidosis, compensatory mechanisms include a respiratory response of increased ventilation resulting in reduction of pCO2. This temporarily minimizes the fall in blood pH. But long term correction of a metabolic acidosis requires renal bicarbonate retention and enhanced acid excretion. Clinical findings: - Acidosis causes increased heart rate and cardiac output due to activation of sympathetic nervous system, also there is an increase in depth and rate of respiration due to stimulation of respiratory center caused by an increase in CO2 tension of blood and depletion of bicarbonate. - Calves affected with severe acidosis and dehydration due to acute diarrhea (with severe hypovolemic shock), there is depression of respiratory rate and depth of respiration resulting in accentuation of acidosis due to additional hydrogen ions. - Acidosis causes CNS depression and muscular weakness, increased urinary excretion of acids cause polyuria which may be severe to cause dehydration or accentuate concomitant dehydration. - Concomitant hyperkalemia will cause bradycardia, sudden collapse and rapid death. Treatment: IV administration of isotonic sodium bicarbonate solution (2.5- 4.5 liters, 1.3%) depending on the severity of the condition. Alkalosis - Metabolic alkalosis is characterized by an increase in pH and bicarbonate caused by excessive hydrogen ions loss (acid), bicarbonate retention or contraction alkalosis. Contraction alkalosis occurs when extracellular
Systemic states. 21
Dr. Ghalib/ Internal Medicine lectures/ Systemic states/ Fourth year.
-
-
-
-
fluid (ECF) volume is reduced because of loss or sequestration of fluid high in sodium and chloride but without loss of bicarbonate. Alkalosis occurs in domestic animals in cases of abomasal dilatation (cause abomasal atony), impaction or torsion of abomasums are the commonest causes of alkalosis in cattle. There is continuous secretion of HCL and K into the abomasums with failure of evacuation into the duodenum for absorption. Sequestration of HCL and K occur in abomasums along with reflux into the rumen resulting in hypochloremic hypokalemic alkalosis. In metabolic alkalosis, excessive HCO3 administered is an additional potential cause. Potassium will shift from ECF to intracellular space resulting in hypokalemia although there is no depletion of potassium. In cattle with metabolic alkalosis, there is paradoxic acid urine which is not well understood but may be due to severe electrolyte depletion which limits the ability of kidney to regulate acid-base balance. There are no characteristic clinical signs of alkalosis. It may results in shallow slow respiration in attempt to preserve CO2. Muscle tremors, tetany and convulsion may occur due to depression of ionized calcium in the serum. Acidifying solution (isotonic) of mixture of ammonium chloride and potassium chloride, or a mixture of Isotonic KCL (1.1%) 1 liter Isotonic NaCl (0.9%) 2 liter Dextrose (5%) 1 liter
Metabolic profiles test The term metabolic profile is used to describe a system of serological monitoring of dairy herds as an aid in the assessment of their nutritional, metabolic and health status. MPT is a reliable test for the early diagnosis of nutritional deficiency or metabolic disease for optimal livestock production and to obtain maximum yield at minimum costs. Blood parameters: Blood glucose, PCV, hemoglobin, blood urea nitrogen (BUN), serum inorganic phosphate, magnesium, calcium, potassium and sodium parameters may be measured.
Systemic states.
22
Dr. Ghalib/ Internal Medicine lectures/ Systemic states/ Fourth year.
Other laboratory analyses may be occasionally done are: a- Serum copper b- Serum iron c- Plasma free fatty acids. At the time of sampling, the following information should be collected A- Information related to the individual animals sampled. 1- Age 2- Milk yield 3- Date of calving 4- Amount of concentrate fed per day. B- Information relating to the whole herd. 1- Total herd production and number of cows in milk. 2- Recent data on bulk milk quality. 3- The individual daily yield of 6 cows past their peak of milk production on 3 consecutive occasions. 4- Estimation of the average daily forage intake. 5- Analyses of forage and grains. Animals to be sampled: Blood samples were collected from 3 groups of 7 high yield lactating cows, 7 medium yield cows and 7 dry cows. - The samples are collected at least 3 times yearly summer, autumn and winter or when nutritional imbalance is suspected. - The samples should be collected at the same time of day and should be dispatched to the laboratory within few hours and not subjected to heat or cold. - Blood samples may be taken from jugular or coccygeal veins but not from mammary vein.
Interpretation of results: - It can be difficult; the major objective is to slow the relationship between blood components, nutrition, productivity and fertility. The results may show variations between herds and next between lactating groups within herds. One of the major difficulties is to identify the common causes of variation. - Blood glucose is commonly used as indicator of energy status. Glucose level may be variable depending on the fluctuations in daily feed intake beside nonnutritional factors such as: - Stress - Excitement - Severe cold
Systemic states. 23
Dr. Ghalib/ Internal Medicine lectures/ Systemic states/ Fourth year.
- Corticosteroid therapy. - Estimation the level of free fatty acids are more sensitive than blood glucose as an indicator of energy status of lactating cows but it may be variable during early lactation which limit its usefulness. - Concentration of BUN has a direct relationship with protein intake. Low concentration of urea indicates that protein intake is minimal and early warning that low protein status may develop later if protein is not increased. - Mean values of PCV, Hb and serum iron are higher in non-lactating cows than in lactating cows. - Serum inorganic phosphate levels tend to fall when dietary intake is sufficient for longtime hyperphosphatemia may occur in cattle grazing on highly fertilized pasture. - Serum calcium levels vary only within narrow limit and so are not sensitive indication of input-output balance but low calcium levels in late pregnancy indicate a dangerous situation. - Low levels of serum sodium occur in early lactation in cows. It also associated with depraved appetite and polydipsia and polyuria. - Serum potassium levels are difficult to interpret because its levels are not necessarily indicative of potassium deficiency. - Metabolic profile may aid in examination of feeding system and feedstuffs, management and clinical cases. The test is probably useful for diagnosis and prognosis in extreme variations from normalcy.
Systemic states.
24