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In this section, the student is introduced to the broad discipline of veterinary pathology. The basic information provided will be helpful in understanding or developing an appreciation for ways in which living tissues respond to injurious agents. The role of pathology in veterinary medicine, historical aspects of medicine, basic language of pathology, ways in which the body responds to injurious agents, means of detecting disease after death of the entire body, and causes of cell injury and/or disease, are discussed.
The terminal objectives and list of key words, outlined below, should be reviewed as the need arises. They student may which to monitor the amount of information retained by providing appropriate answers for the post-instructional self-study questions included at the end of this section.
At the completion of this section, the student should be able to perform the following tasks.
Hippocrates William Harvey, Edwin Kleb
Aristotle ,Carl Rokitansky ,Julius Cohnheim
Claudis Galen Rudolph, Virchow, William Welch
Cornelius Celsus ,Louis Pasteur, Giovanni Morgangi
Renatus Vegetius ,Robert Koch
Please attempt to define, spell and use the following terms before and after embarking on a study of this section.
The term pathology is used when one refers to the "scientific study of disease" or the alterations that occur when abnormal influences (bacteria, viruses, etc.) affect cells, tissues, or body systems. More specifically, pathology may be defined as the "scientific study of the molecular, cellular, tissue, or organ system response to injurious agents or adverse influences."
For more than a hundred years, pathology has been one of the "keystones" of medicine. As an academic subject, it is taught as part of the veterinary curriculum to prepare the student for courses in clinical medicine and surgery. It serves as a "bridge" or "link" between the preclinical subjects (anatomy, physiology, etc.) and the courses in clinical medicine. Actually, pathology provides a logical means of relating the knowledge of normal structure and function (anatomy and physiology) to abnormal structure and function as encountered in a diseased animal. Thus, the factual background or knowledge needed for logical reasoning when solving real-life clinical problems is provided. It should be emphasized that pathology, as the scientific study of disease, follows the morbid process from its inception to its termination, and investigates the lesions produced. Therefore, a sound knowledge of pathology is the foundation of a solid understanding of disease as it occurs in the living patient.
Pathology has its roots deeply implanted in medical history. The earliest observers, from Celsus (about 30 B.C. - A.D. 38) to Morgagni in the 18th century, based their work upon the naked-eye appearances of diseased individuals and organs. Only as the technique of light microscopy improved was the Germanic School of Pathology, headed by Virchow (1821-1905), able to investigate changes at the cellular level. Today, technological advances are occurring so rapidly that no veterinarian can hope to have a working knowledge of all the methods available to study disease. Regardless, it is by utilizing all these complex techniques that problems are fully investigated. Thus, the student of medicine should have some understanding of the techniques which are available, and the types of problems which they might be able to solve. In this way, investigators conversant with many different disciplines are brought together to their mutual benefit. Techniques available in pathology include light microscopy, electron microscopy, microdissection, immunological techniques, ultracentrifugation, electrophoresis, chromatography, radioactive isotope technology, tissue culture, etc.
In summary, pathology is one of several mechanisms employed to solve those problems encountered in clinical situations. Thus, the student is required to make practical use of information accumulated in the General and Special Pathology courses. The compartmentalization and storage of knowledge for examination purposes is an exercise in futility. However, the utilization of accumulated knowledge in understanding clinical problems is an educational reality.
AGreek physician, introduced the humoral theory of disease. He recognized four humors or fluids in the body:
Health was thought to be due to proper mixing of these four humors, while disease resulted from improper mixing. The humoral theory of disease was supported by three critical observations:
Also, what was called phlegm is the same as fibrin. Those factors considered to be the effects of disease today were considered as causes by the humoral pathologists. The early humoral pathologists were not permitted to perform postmortem examinations on humans; thus, a confused concept of normal anatomy existed. Hippocrates is considered to be the Father of Medicine.
A Greek philosopher, was the originator of modern anatomy and physiology. Also, he is considered to be the Father of Zoology. Aristotle dissected many animals, carried out experiments in physiology, and studied the growth and development of animal life (human autopsy examinations were forbidden during this period).
A Greek physician practicing in Rome, was a follower of the beliefs of Hippocrates. Humoral pathology was brought to its height and most extreme development by Galen. Also, he wrote numerous medical documents and held despotic authority over European medicine for thirteen centuries after his death. Also, Galen is remembered for his views on meat inspection. He insisted that animals used for human food should be inspected prior to slaughter.
Was not a physician, but a man of leisure with a variety of interests. A great deal of the history of the early humoral pathologists was recorded in his work. A great number of the conditions recognized today are described in the work of Celsus. His writings described and discussed the cardinal signs of inflammation (redness, swelling, heat and pain).
A Roman veterinarian, is credited with being the first author to write a textbook devoted exclusively to veterinary medicine. He was among the first to urge people to disregard Divine Displeasure as the cause of disease and to base their treatment and concepts of disease on a thorough knowledge of anatomy, surgery and medicine. Vegetius is considered to be the Father of Veterinary Medicine.
Described the blood vascular system and the circulation of blood in 1628. His works have had a far reaching effect on medicine and pathology.
Was the first to show that the microscope had practical importance in the study of tissues and other small objects (he is not credited with discovering the microscope).
A Frenchman, was one of the first to describe diseases according to organs or parts of the body. he generally divided his diseases into those affecting parts above the diaphragm, those involving parts below the diaphragm and external diseases. One of his books, entitled Pathologiae Libri, was the first medical work to be called a text of pathology.
An Italian, is recognized as one of the earliest pathologists and the originator of modern pathology. He was the first to correlate pathologic changes in the dead individual with clinical signs and symptoms shown by the individual during life.
A Frenchman, is credited with establishing the foundation for the study of histology, even though most of his work was done by physical and chemical methods (he did not possess a microscope). Bichat presented a new concept of anatomy and showed that the body was composed of twenty-one (21) tissues (vascular, osseous, muscular, cartilaginous, etc.). He is considered to be the Father of Histology.
Published the first complete veterinary classic of this period, entitled Le Parfait Marechal. In this publication, Solleysel pointed out the adverse situation created by allowing the veterinary art to fall so completely into the hand of the Farrier. This book marks the beginning of the end of the horseshoer's regimen and control of veterinary medicine.
A French veterinarian, was gifted in equine husbandry and wrote a book, entitled Elements of Hippiartry and the New Knowledge of Equine Medicine. He investigated and was successful in eradicating an outbreak of glanders in French Calvary horses. He was instrumental in establishing the first modern veterinary school in Lyon, France. In addition, Bourgelat established the veterinary school known as L-Ecole Veterinaire Nationale d'Alfort, located near Paris, France.
A German, is considered as the supreme descriptive pathologist of all time. He firmly established the structural basis of disease as well as necropsy technique. However, he explained practically all diseases on the basis of blood anomalies.
Is known as the Father of Cellular Pathology.
He coined and explained many of the terms and concepts used today in pathology (amyloidosis, fatty degeneration, etc.). In addition, he started publication of "Virchow's Archives," a journal that has been in continuous publication since 1847. This is considered to be one of the most complete works of pathology in existence.
Frenchman, was one of the originators of the field of bacteriology. He demonstrated the importance of infectious organisms (bacterial) in disease. Pasteur studied human and animal diseases (pasteurellosis, anthrax, rabies, etc.) and showed that individuals could be successfully immunized by vaccines prepared from organisms.
A German bacteriologist, established the Koch's Postulate, a procedure employed for proving a specific microorganism as the cause of a disease. He was the first to use artificial solid media in the attainment of pure cultures.
A student of Virchow, demonstrated the importance of bacteria in pathology.
A student of Virchow, is credited with being the originator of modern experimental pathology. He revealed the vascular alterations that are the basis of the inflammatory response.
A student of Cohnheim, is credited with bringing pathology to the United States. He was Professor of Pathology at John Hopkins University in Baltimore, Maryland.
In order for a subject or course to be meaningful, one should become familiar with the basic terminology applicable to that subject. Listed below are a few basic terms used repeatedly in pathology and/or veterinary medicine. The student should become familiar with these terms and their definitions.
1.6.1 DISEASE:
A disease may be defined as a "state in which an individual exhibits an anatomical, physiological, or biochemical deviation from the normal." As generally used, the term "disease" is employed to describe a state in which there is sufficient departure from the normal for clinical signs or symptoms to be produced.
1.6.2 LESIONS:
The term lesion is generally used to refer to "structural or morphological alterations associated with a diseased state in an individual." It is the objective deviation from the normal.
Lesions may be recognized with the naked-eye (gross lesions), with the aid of a light microscope (microscopic lesions), or with the aid of the electron microscope (ultrastructural lesions). Biochemical or functional lesions are recognized as changes which result from disturbed function.
Pathognomonic Lesion: refers to a change which is specifically characteristic of a disease. When one sees a pathognomonic lesion, he knows that a particular disease is present.
1.6.3 HEALTH:
As generally used, the term "health" refers to the "state in which an individual is living in complete harmony with his environment," it is a relative state. All body functions are performed normally even though lesions may be present in organs and/or tissues. It should be remembered that the transitional zone between health and disease is difficult to define.
1.6.4 ETIOLOGY:
The term "etiology" refers to a "study of the cause of a disease." An etiologic agent is the factor (bacterium, virus, etc.) responsible for lesions or a disease state.
Predisposing Causes of Diseases: refer to those factors which make an individual more susceptible to a disease (damp weather, poor ventilation, etc.)
Exciting Causes of Disease: refer to those factors which are directly responsible for a disease (bacteria, viruses, hypoxia, chemical agents, etc.).
1.6.5 CLINICAL SIGNS:
"Clinical signs" refer to any "functional evidence of disease which can be determined objectively or by the observer" (lameness, salivation, increased respiratory efforts, etc.). Remember, clinical signs are seen only in the living individual.
The term clinical symptoms should be reserved for any "functional evidence of disease that can be determined subjectively or by the patient" (feeling or abdominal discomfort, etc.). The term "clinical sign" is preferred in veterinary medicine.
PROGNOSIS:
The term "prognosis" refers to the probably outcome of a disease in a living individual. It is the clinician's estimate of the severity and possible result of a disease.
DIAGNOSIS:
The term "diagnosis" refers to the "determination of the nature of a disease expressed in a concise manner."
A morphologic or anatomic diagnosis is based on the location and nature of the lesion (hemorrhagic enteritis, etc.). Etiologic diagnosis is made on the basis of the cause (dirofilariasis, etc.). Definitive diagnosis is made on the basis of the specific disease entity involved (canine distemper, etc.). A clinical diagnosis is made on the basis of clinical signs observed in the living animal.
1.6.8 PATHOGENESIS:
The term "pathogenesis" refers to the "progressive development (sequence of events) of a disease from the time it is initiated to its final conclusion in recovery or death."
1.6.9 NECROPSY:
Common usage of the term "necropsy" in veterinary medicine refers to gross examination of the carcass by systematic dissection in order to evaluate any abnormal changes (lesions) that may be present. However, a complete necropsy refers to all postmortem examinations including gross, microscopic, toxicologic, and microbiologic examinations. The term "autopsy," used synonymously with necropsy in human medicine, has been avoided in veterinary medicine because of the prefix "auto" meaning self, implying self-examination.
Biopsy refers to the removal and examination of tissue obtained from the living body.
Euthanasia refers to the intentional "putting to death" of an individual with an incurable or painful disease by employing humane means.
1.6.10 SOMATIC DEATH:
The term "somatic death" refers to death of the entire body; there is cessation of all body functions. The absence of heart beat, pulse, respiration or brain waves has been used to define somatic death.
Necrobiosis refers to death of cells at the end of their normal life-span within the living body (epithelial cells of the skin, leukocytes, etc.). Cell death occurs without harm to the individual because "normal functions" have been fulfilled.
Necrosis refers to the morphological changes caused by the progressive degradative action of enzymes on the lethally injured cell within the living body. After a cell dies, lysosomes rupture and their hydrolytic enzymes are released. The release and activation of these lysosomal enzymes are responsible for cell necrosis. Remember, necrotic cells are dead cells, but dead cells are not necessarily necrotic.
1.6.11 POSTMORTEM CHANGES:
"Postmortem changes" refer to cell death which accompanies or occurs after death of the entire body (somatic death), whereas antemortem changes refer to those alterations that occur in cells, tissues, organs, etc. prior to somatic death or in the living individual. It is important to differentiate postmortem changes from antemortem changes in order to interpret correctly those lesions encountered at necropsy.
Remember, postmortem changes develop only after the individual dies.
Postmortem Autolysis refers to self-digestion by enzymes that are present within or released into the cytoplasm of cells after death. It is due to total diffuse anoxia.
Postmortem Putrefaction refers to the decomposition of tissues by bacterial enzymes after death of the entire body.
Rigor Mortis refers to stiffening of all muscles after death. It is related to a progressive decrease in oxygen, ATP, creatinine phosphate, and pH of muscles. Thus, muscle fibers shorten as they pass into rigor. Classically, rigor mortis begins in one (1) to six (6) hours after death and disappears 24 to 48 hours later.
Postmortem Clotting of Blood refers to the coagulation of blood in vessels and/or heart after somatic death. Postmortem clots may be dark red (current jelly clots) or the yellow color of plasma (chicken fat clots). Such clots are smooth, shiny, uniform in texture, and unattached to the vessel or heart wall. On the other hand, antemortem clots or thrombi are friable, dull colored, roughened over the surfaces, and attached to the vessel wall.
1.6.12 EPIZOOTIOLOGY:
The term "epizootiology" refers to the science that deals with epidemics of disease among lower animals (occurrence and spread of disease in relation to geographical location, season, species, breed, age, sex, etc.).
- Morbidity: refers to the occurrence of disease in relation to the number of animals exposed (ratio of sick to well animals in a community).
- Mortality: refers to the number of deaths that results from disease.
- Mortality Rate: refers to the number of deaths compared to the total animals of the same species in a group or area.
- Case Fatality Rate: refers to the ratio of deaths to the number of animals affected with a disease.
There are many terms applied to different branches or phases of pathology. Among these are the following:
1.7.1 GENERAL PATHOLOGY:
Refers to the study of the basic alterations in tissues. These are changes which apply to most of the organs or tissues of the body and include such things as atrophy, necrosis and inflammation..
1.7.2 SYSTEMIC PATHOLOGY:
Refers to the study of the diseases of the organ systems of the body such as the respiratory system, digestive system and nervous system.
1.7.3 GROSS PATHOLOGY (macroscopic pathology, pathological anatomy,morbidanatomy):
Refers to the study of disease in which tissues and organs are examined with the unaided eye.
1.7.4 CELLULAR PATHOLOGY (microscopic pathology, histopathology):
Refers to the study of diseased tissues and organs with the aid of a microscope.
1.7.5 SURGICAL PATHOLOGY:
Refers to the study of tissues removed at the time of surgery.
1.7.6 CLINICAL PATHOLOGY:
Refers to the study of disease by examination of blood, urine, feces, skin scrapings, etc.
1.7.7 IMMUNOPATHOLOGY:
Refers to the study of diseases associated with abnormalities of the immune mechanisms of the body.
1.7.8 CHEMICAL PATHOLOGY:
Refers to the study of chemical changes in the fluids and tissues of the body as the result of disease. This branch of pathology is merely a portion of clinical pathology.
1.7.9 PHYSIOLOGICAL PATHOLOGY:
Refers to the study of the changes in the functions of organs or parts of the body as a result of disease.
1.7.10GEOGRAPHICAL PATHOLOGY:
Refers to the study of the disease processes in population groups in different parts of the word. As an example, certain diseases of the heart and major blood vessels in man are much more prominent in the United States than in the Orient or other parts of the world.
The "case" outlined below may assist the student in gaining a working knowledge of terms commonly encountered in pathology.
"A 12-year old German Shepherd was presented to the veterinary clinic with a history of depression, discolored mucous membranes, and difficult breathing following exercise. A physical examination performed by the attending clinician revealed exudate around the nostrils, increased pulse rate, and abnormal heart sounds (clinical signs). It was concluded that the dog had signs suggestive of heart failure and pneumonia (clinical diagnosis). The owner was told that the dog would most likely die even after intensive treatment (prognosis). A few days later, the owner suggested that the dog be put to death in a humane manner (euthanasia), and systematically dissected (necropsy examination). When the organs and tissues were inspected with the naked-eye (gross examination), approximately 40% of the total lung mass was consolidated and multiple small abscesses were distributed throughout all lobes (lesions). Also, the right ventricular wall was markedly thickened and its lumen contained numerous Dirofilaria immitis (etiologic agent). Based on the gross findings, it was concluded that the dog suffered from dirofilariasis (etiologic diagnosis) and suppurative bronchopneumonia (morphologic diagnosis). Tissues were collected for testing for microorganisms (microbiologic examination) and for examination with the aid of a light microscope (histopathologic examination). On microbiologic examination, Staphylococcus aureus (etiologic agent/exciting cause) was recovered from the lung abscesses. On microscopic examination of tissue sections of the lungs, there were well-defined collections of neutrophils as well as dead and dying parenchymal cells (microscopic lesions). In addition, numerous inclusion bodies (pathognomonic lesion) specifically characteristic for canine distemper (definitive diagnosis) were found within bronchial epithelial cells. Based on the lesions and laboratory findings, the pathologist attempted to reconstruct the sequence of events from the point at which they began through their entire development (pathogenesis)."
RESPONSE OF THE BODY TO INJURIOUS AGENTS:
Since pathology deals with disease, it is appropriate at this time to consider some of the ways in which the body responds to injurious agents (bacteria, viruses, trauma, etc.). Initially, the body employs one or more of its natural defense mechanisms. These defenses include physical barriers (skin, mucous membranes, etc.), detoxification (neutralization of toxin by liver enzymes, etc.), adaptive compensation (increase in heart size when it is overloaded, etc.), immunologic response (reaction of antibodies with antigens, etc.), cellular response (movement of neutrophils toward an injured site, etc.) and others. The natural body defenses may completely neutralize or destroy the injurious agent before lesions and/or disease develop. However, once lesions and/or disease are detected, it can be assumed that natural body defenses were inadequate or at least tardy in their response. As a result, an inflammatory response may develop.
Inflammation is one of the primary host defense mechanisms against all forms of tissue damage. It can best be defined as the "vascular and cellular response of living tissue to injury."
Thus, the inflammatory process serves to dilute, neutralize, destroy or wall-off the injurious agent as well as damaged parenchymal cells. In other words, a complex series of events are initiated which, as far as possible, heal and reconstitute the damaged tissue. It should be remembered that inflammation and repair of tissues occur together.
On the whole, inflammation and repair are beneficial to the host. In their absence, infections would go unchecked, burns would not heal, and wounds would remain festering open sores. However, under certain circumstances, inflammation and repair may be harmful to the body. Also, the inflammatory process and other body defenses may not be effective in controlling an infection and somatic death ensues. Remember, the inflammatory response is encountered on a continuous basis throughout the study of clinical medicine and surgery.
The inflammatory response and repair are considered in greater detail in sections VIII and IX of this syllabus.
At this point, the student has gained an appreciation for some common terms used in pathology as well as an insight into ways in which the body responds to injurious agents. Thus, it is now appropriate to consider procedures commonly employed to detect disease after somatic death. Remember, the term "necropsy" refers to the examination of a carcass by systematic dissection (gross examination). However, a complete necropsy refers to all postmortem examinations, including gross inspection, microscopic, microbiologic and toxicologic examinations. Actually, a necropsy examination should be the "cornerstone" of every veterinary practice's quality control program. It provides new insights into the cause and incidence of disease, as well as an objective retrospective assessment of the original clinical diagnosis. Remember, most necropsies are performed to determine the exact cause of death and for continuing educational purposes.
The carcass should be necropsied as soon as possible after death to minimize postmortem autolysis and putrefaction. Prior to the necropsy examination, the case record or "necropsy request form" and other pertinent background information are reviewed. The entire carcass, including organs and tissues are examined in a systematic manner. Specific necropsy techniques are discussed in more detail during lecture sessions and when the student is assigned to the necropsy laboratory.
During the necropsy examination, appropriate specimens are collected for various laboratory tests (histopathologic, microbiologic, toxicologic examinations).
If there is a need to examine lesions, etc. with the aid of the light microscope, tissue specimens are collected and placed in a 10% neutral-buffered solution of formalin which is the best general fixative available. It serves to
The following guidelines should be adhered to when collecting tissue samples for histopathologic examination.
It is the responsibility of the clinical microbiologist to identify microorganisms (bacteria, viruses, fungi, yeast) from tissues submitted by the pathologist or clinician. The results may determine the cause of a disease, type of treatment administered, or establish the cause of somatic death. The following guidelines should be adhered to when collecting tissue at necropsy for bacteriologic examination:
Are collected and preserved in the manner described for microbiologic specimens. However, freezing is permissible if the time period between collection and examination of specimens is prolonged.
Should be placed in a sterile, dry, screw-capped tube (do not place specimens in transport media or in a moist tube).
Are collected (brain) and submitted to the State Health Laboratory for analysis (students at Tuskegee institute are not permitted to handle or perform necropsy examinations on carcasses suspected of rabies, undetermined neurologic diseases, and/or highly contagious diseases).
The tissue samples collected for toxicologic examination are dictated by the toxic agent suspected. If poisoning of undetermined origin is suspected, adequate amounts of stomach contents, urine, blood, liver and kidney should be collected during the necropsy. Each specimen is placed in a separate clean container and frozen until analyzed (do not use a preservative such as formalin, etc.).
At this point in time, the student has been exposed to the basic language of pathology, ways in which the body responds to injurious agents, and the means by which diseases are detected. The final phase is to place these elements in perspective for the student by utilizing a disease model. Since canine distemper is used as the disease model, the student is asked to review the following summary.
Canine distemper is a highly contagious disease caused by a paramyxovirus. The disease occurs primarily in young dogs and is characterized by a visceral phase as well as by an encephalitic phase. The virus in combination with bacterial infections is responsible for the clinical signs observed during the visceral phase (ocular and nasal discharges, pneumonia, enteritis, skin vesicles and pustules, etc.). Dogs that survive the visceral phase may succumb subsequently to central nervous system complications. Significant clinical findings include a diphasic temperature elevation, ocular and nasal discharges, respiratory distress, enteritis, and nervous signs (characterized by chewing movements, excessive salivation, epileptiform seizures, blindness and paralysis).
Gross lesions in the visceral phase depend on the extent and severity of secondary bacterial infections (pneumonia, enteritis, etc.). The virus produces intranuclear and cytoplasmic inclusion bodies in epithelial cells (respiratory, urinary, digestive, etc.). The virus of canine distemper in combination with Brucella bronchiseptica is considered to be the cause of the respiratory lesions associated with this disease. The virus attacks epithelial cells and renders the lungs more susceptible to bacterial invasion. Lung lesions are often times manifested by a purulent bronchopneumonia when secondary bacterial invasion is present. The virus alone, stimulates an interstitial reaction with or without multinucleated giant cells. Cytoplasmic and nuclear inclusion bodies are formed in epithelial cells (bronchial epithelial cells, etc.) by the virus.
In the central nervous system, the virus has an affinity for the myelinated portion of the brain and spinal cord. The cerebellar peduncles, anterior medullary velum, myelinated tracts of the cerebellum and the white columns of the spinal cord are the structures most constantly affected. Central nervous lesions consist of demyelination, gliosis, perivascular cuffing and inclusion bodies within glial cells and neurons. A clinical diagnosis of canine distemper is best confirmed by histopathologic lesions (inclusion bodies, demyelination, etc.) and/or by the fluorescent antibody technique.
Before embarking on a study of the stressed, injured, or dead cells, the student should be familiar with some of the factors responsible for alterations at the cellular, tissue and organ levels. The biochemical and morphologic changes discussed in subsequent sections of this course are induced by various forms of stress, including bacteria, viruses, trauma, chemicals, etc. However, it should be remembered that the response of the host to stress, as well as to environmental factors which may influence the manner in which cellular injury or a disease is expressed. Most forms of stress (injurious agents) affect fundamental cellular mechanisms or components such as:
If enough cells are injured, functional disturbances occur and morphologic alterations can be observed with the naked eye, with the aid of the light microscope, or by employing the electron microscope.
1.19.1 PREDISPOSING CAUSES OF CELL INJURY/DISEASE:
Predisposing causes refer to those factors which confer a tendency to disease or those which make a host more susceptible to disease. Predisposing causes of disease may be divided into intrinsic and extrinsic causes.
- --Intrinsic predisposing causes refer to those factors which determine the type of disease present within a host. These factors include genus, race, breed, family, age, sex, color, etc.
- --Extrinsic predisposing causes refer to factors operating from the external environment which tend to make an animal more susceptible to disease, especially those caused by infectious agents. These factors include nutritional deficiencies, chilling, dampness, poor ventilation, etc. Environmental factors are perhaps the most important extrinsic predisposing causes of disease. These factors may change subclinical or latent infections into acute or chronic diseases.
1.19.2 EXCITING CAUSES OF CELL INJURY/DISEASE:
Exciting causes refer to those factors or influences directly responsible for disease. Most of these adverse influences can be grouped into the following broad categories:
- (1) hypoxia,
- (2) physical injuries,
- (3) chemical injuries,
- (4) biological agents such as bacteria, viruses, fungi, etc.,
- (5) altered immune mechanisms,
- (6) genetic defects and
- (7) nutritional imbalances.
These causative factors are discussed briefly.
1.19.2.1 HYPOXIA :
Hypoxia refers to a lack of oxygen which is probably the most common cause of cell injury and disease. It may be the ultimate mechanism of damage initiated by a variety of physical, chemical and biological agents. Hypoxic injury to cells may be caused by:
- (1) loss of their blood supply (e.g. ischemia subsequent to the presence of a thrombus in the lumen of a vessel),
- (2) depletion of the oxygen-carrying capacity of the blood (e.g. carbon monoxide poisoning in which monoxyhemoglobin replaces oxyhemoglobin and blocks the normal transport of oxygen),
- (3) poisoning of the oxidative enzymes within cells (e.g. cyanide poisoning in which cytochrome oxidase is inactivated).
Ultimately, all of these derangements affect aerobic respiration.
1.19.2.2 PHYSICAL INJURIES:
Physical agents responsible for cell/tissue damage include trauma, pressure, obstructions of hollow organs, malpositions, thermal factors, changes in atmospheric pressure, light, electricity and radiation.
1.19.2.2.1 MECHANICAL TRAUMA:
Is usually an injury caused by sudden violent physical forces in which cells/tissues are torn or crushed. The types of trauma include:
- --Contusion (bruise) refers to an injury in which the covering skin is intact, but the underlying tissues are damaged.
- --Abrasion refers to an injury similar to a contusion, but one in which the skin is broken.
- --Incision refers to an injury produced by a sharp object, resulting in little tissue damage.
- --Laceration refers to an injury resulting from the tearing or tissues with a blunt object.
- --Perforation refers to a wound in which the point of entry of the mechanical force is small.
- --Rupture refers to a injury in which tissues are stretched until the fibers are disrupted (rupture occurs in hollow organs or in the capsule of such organs as the kidneys, liver and spleen or in muscles and tendons).
- --Fracture refers to a break in a hard substance such as bone or cartilage. A clean break, separating a bone into two parts, is called a simple fracture. If there are many parts, it is a comminuted fracture. If in addition to the break in the bone, there is an opening in the overlying skin, the lesion is a compound fracture. A fracture in which the periosteum remains intact and holds the ends of bone in place is a greenstick fracture.
- --Luxation (dislocation) refers to an injury of an articulation in which there is displacement of bone making up the articulation.
1.19.2.2.2 PESSURE:
Results in mild or less violent injuries which usually take place over a prolonged period of time.
- --Decubitus ulcers or bed sores which occur over bony prominences of the body (tuber coxae, zygomatic arch, etc.) of an animal recumbent for several days is a classical example of pressure injury. Also, pressure injury occurs when casts or bandages are applied too tightly or when neoplasms, abscesses, etc. encroach upon parenchymal organs.
1.19.2.2.3 OBSTRUCTION OF HOLLOW ORGANS:
Hollow organs may be obstructed and subsequently injured by changes within the lumen (rubber ball, etc.), pressure from outside the organ (neoplasm, etc.) or by changes within the wall of the organ (abscesses, neoplasm, etc.).
- --The term "stenosis" refers to any narrowing of the lumen of a hollow organ; whereas the term "stricture" is reserved for a form of stenosis caused by contraction of fibrous connective tissue (scar tissue) in the wall of an organ.
1.19.2.2.4 MALPOSITION:
Refers to the displacement of an organ or part that results in cell and/or tissue injury. The types of malpositions include the following:
- --Volvulus refers to the rotation of an organ or part around its mesenteric base of attachment. Loops of intestine are usually involved and the twist is usually more than 180 degrees.
- --Torsion refers to the rotation of an organ or part along its own long axis. The intestine, uterus, lung lobes, etc. may be involved.
- --Intussusception refers to the telescoping of one portion of a hollow organ into another portion (e.g., a portion of the intestine is forced inside the segment just posterior to it).
- --Prolapse is the appearance of an organ or portion of an organ at a natural or artificial body opening.
- --Hernia is the protrusion of an organ through a natural or an artificial body opening with the organ being covered with skin or the parietal layer of a serous membrane. It consists of three parts: the hernial ring, the hernial sac, and the contents.
1.19.2.2.5 THERMAL INJURIES:
Extremes of temperature, such as freezing and burning, cause injury in several ways (direct damage, vasconstriction, etc.).
- --Burns refer to lesions produced directly by heat. Depending upon the extent of the injury, burns are classified as:
- (1) first degree burns (characterized by reddening of tissues),
- (2) second degree burns (characterized by blister formation),
- (3) third degree burns (characterized by death of cells and tissues or necrosis) and
- (4) fourth degree burns (characterized by charring of tissues).
- --Heat retention (heatstroke/sunstroke) occurs when animals are unable to eliminate sufficient heat to maintain body temperature at a level compatible with life. Subsequently, cells and tissues are injured. Essential signs are high fever (106 to 110 degrees F), respiratory distress, discomfort, excitement, collapse, and sudden death.
- --Freezing of tissues occurs when the body is exposed to very low temperatures. When tissues freeze, there is damage to blood vessels, formation of thrombi and subsequent interference with circulation (sloughing of tissues such as the tip of the ears or other extremities may occur).
1.19.2.2.6 LIGHT:
Sunburn or overexposure to light is rare in animals due to skin pigmentation and protection by the hair coat. Photosensitization with damage to the skin occurs as the result of the action of sunlight on fluorescent pigments (phylloerythrin, etc.) in the skin.
1.19.2.2.7 ELECTRICITY:
Strong electrical currents from artificial sources or from lightning cause burns or result in somatic death. An animal produces a short circuit with his body between two conductors. The effects of electricity include burning of tissues, hemorrhages, and/or death due to interference with cardiac and respiratory functions.
1.19.2.2.8 .RADIATION:
Injuries produced by ionizing radiation depend upon the type of radiation (alpha, beta, gamma, etc.) and the susceptibility of the cell or tissue exposed. Rapidly growing cells (e.g., lymphoid cells) are quite susceptible; whereas, more slow growing cells (e.g., cells of bone) are more resistan
1.19.2.3 .CHEMICAL INJURIES:
The list of chemical that may produce cell/tissue injury defies compilation. Simple chemicals such as glucose or salt in hypertonic concentrations may cause cell injury by deranging the fluid and electrolyte homeostasis of cells; even oxygen in high concentrations is severely toxic. On the other hand, the levels of toxicity of certain substances are so high that they are known as poisons and trace amounts (arsenic, cyanide, mercury salts) may destroy a sufficient number of cells within minutes or hours to cause death. Under certain conditions, toxic materials may be formed within the body and subsequently cause cell damage. Severe burns, uremia, and gangrene may be associated with endogenous poisons.
1.19.2.4 BIOLOGICAL AGENTS:
Biological agents are important causes of cell injury and death. They include bacteria, viruses, rickettsiae, fungi and higher forms of parasites. The ways in which this heterogeneous group of biological agents cause injury are diverse and in many cases unknown (please refer to chapter 7 in your textbook).
Bacteria cause cell injury by means of various mechanisms. Certain bacteria, for example, elaborate exotoxins that inhibit oxidative processes and protein synthesis in cells. Other bacteria (e.g., gram negative bacilli of the gastrointestinal tract) cause cell injury by the release of endotoxin from their cell walls when the bacteria are killed. The endotoxin causes profound changes in blood vessels and in the coagulation system. Also, bacteria can cause cell injury by the induction of immunologic responses to antigens contained within the microbiologic agent (tuberculosis).
Viruses are infectious particles that contain only one nucleic acid, either DNA or RNA. They do not have ribosomes or other structures that synthesize protein, RNA or metabolic enzymes. Thus, viruses are intracellular parasites that survive within living cells where they subvert the metabolism of the host for their own survival. This results in decreased synthesis of all macromolecules vital to the host. Continued viral replication may therefore interfere with the host's own metabolism. The viral protein elaborated during viral replication may be directly toxic to infected cells. Also, viral RNA or DNA may become incorporated into the genome of the host cell and cause either cell death or cellular transformation and frequently increased cell proliferation. This last effect may lead to tumor formation, a point relevant to the viral causation of cancer in lower animals.
Prions are hypothesized to be the infectious component of spongiform encephalopathies which occur in animals and man. The term is derived from the words proteinaceous infectious particle. Animal diseases associated with this material are scrapie of sheep and bovine spongiform encephalopathy (BSE). An example of this type of condition in man is Jacob-Creutzfeldt disease.
Fungi are single cell, nucleated plant organisms which include a wide variety of pathogenic species as well as yeasts, molds, mushrooms, mildews and other similar organisms. Most fungi are omnipresent in the environment. Host resistance is therefore a dominant factor in disease. Opportunistic fungal infection results when animals are immunosuppressed, when their mechanisms of inflammation are inhibited and when stress is placed upon their systems over long periods.
Metazoan parasites generally cause disease by local destruction of cells of tissue, by their effects on blood circulation, by their effects as space-occupying lesions or by nutritive competition.
Rickettsial infections are caused by obligate intracellular organisms capable of multiplication only within certain cells of susceptible hosts. The organisms are smaller than bacteria and larger than viruses.
Mycoplasma are self-replicating prokaryotes without a cell wall and containing double stranded DNA. They include the pleuropneumonia organisms (PPLO). These organisms are taxonomically separated from bacteria and are capable of causing a variety of diseases in animals and man. They have a predilection for the mucosal surfaces of the host, particularly those of the respiratory tract, conjunctival and articular membranes, and are generally very host specific. Examples of diseases they produce are bovine mastitis, contagious bovine pleuropneumonia (CBPP), keratoconjunctivitis (Pink eye) in calves and enzootic pneumonia in swine.
1.19.2.5 .IMMUNOLOGIC REACTIONS:
Immunological reactions maybe life-saving or lethal. Some immune reactions may cause cell injury and death (anaphylactic reaction to a foreign protein or drug, etc.). also, there is evidence that an immune reaction against "self-antigens" (autoimmunity) is the cause of certain diseases in animals.
1.19.2.6 GENETIC DERANGEMENT:
Genetic defects are important causes of cellular injury. Chapter 7 of your textbook pursues the subject of cytogenetics.
In this section, the student was exposed to a wide variety of information that will be helpful as specific topics in general pathology are developed in subsequent lectures. Hopefully, any frustrations that may have been encountered in dealing with the vast body of new information, seemingly unrelated to previous experiences or future needs, will soon be minimized. Many of the topics introduced in this section will be expanded upon at a later date. At this time, the student should monitor his/her knowledge base by providing appropriate answers for the post-instructional self examination outlined below.
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At this time, the student should be in a position to provide appropriate responses to the following questions. 1.The term pathology is used when one refers to the "scientific study of disease." Please respond to the following by writing "true" or "false" in the spaces provided.
2.Please provide an appropriate response for each of the following:
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