General Pathology

An Introduction to General Pathology

• The term pathology is derived from:
  • Pathos, or suffering
  • Logos, or reasoning/logic.
• Pathology is defined as the study of disease including:
  • Aetiology - causal factor(s)
  • Pathogenesis - the development of the disease within the body.
  • Lesions - the observable structural changes in the tissues and fluids of the body.
  • Pathophysiology - the functional changes in diseased tissues.
  • Sequel - the consequences of the disease in the body.
  • Remote effects - the effect of disease in one tissue on other tissues in the body.

Lesions

• Lesions are the abnormalities or changes seen in living tissues due to disease.
• Observed in
  • The live animal
  • Tissues surgically removed from the live animal
    • Biopsy/ excision
  • Animals soon after death
    • Necropsy, post-mortem examination.

Decription of Lesions

• Descriptions of lesions is very important
• Whole organs, tissues or individual lesions are described under headings such as
  1. Size
  2. Shape
  3. Colour
  4. Weight
     • Generally in relation to body weight
  5. Texture and Consistency
  6. Appearance of the cut surface
  7. Contents of hollow organs
  8. Position, relationships and effects on adjacent tissues

Disease

Definition and Type

• Disease is a definite morbid (illness producing) process, having a characteristic train of symptoms or signs.
  • May affect the whole body or any of its parts.
  • The disease's aetiology, pathology and prognosis may be known or unknown.
• There are two main categories of disease.
  1. Acute
     • Characterised by sudden onset and short duration.
     • The outcome of acute disease may be:
       • Death
       • Resolution due to host defence response or clinical therapy
       • Progression to chronic disease
  2. Chronic
     • Characterised by insidious onset and protracted course.
     • The outcome of chronic disease may be:
       • Progressive destruction of tissue
         • Compromises funtion and endangers life,
       • The halting of the course of disease, with tissue repair by scarring.

Factors Involved in the Development of Disease

• There are three factors which conspire with each other to produce disease.
  1. The individual animal.
     • In particular, the animal's nutritional and immune status
       • This is modified by:
         • Recent or concurrent disease
         • Previous exposure to the agent(s) responsible
  2. The disease-causing agent(s).
     • Most do not cause a uniform pattern of disease
       • Host defences are important in determining the presentation of the disease.
     • An agent's capacity to produce disease depends upon:
       • The dose
       • The virulence of the agent
     • Several agents may be involved.
       • Usually one agent debilitates, allowing others to exert a greater effect within the body
     • The presence of an agent does not necessarily mean it is the cause of the disease!
     • A pathogenic agent may be absent from the tissues, due to:
       • Clinical therapy
       • Host defence systems
  3. Environment, for example:
     • Overcrowding of animals
     • Mixing animals from differing origins
       • Carriers are allowed to infect susceptible animals.
         • Carriers are animals which harbour the pathogenic agent but do not show signs of disease.
     • Changes in management routine

Types of Agents Causing Disease

1. Infectious organisms
   • Viruses
   • Bacteria
   • Fungi
   • Parasites
2. Physical
   • Trauma
   • Pressure
   • Heat
   • Cold
   • Radiation
3. Chemical
   • Toxic organic and inorganic substances
   • Toxins produced by infectious organisms
4. Nutritional
   • Deficiencies of vitamins and trace elements
   • Excess vitamins and trace elements
5. Genetic defects
   • There is a very wide range of potential defects.
     • Some are incompatible with life
     • Others affect specific systems within the body

Aspects of Disease

• There are many aspects of a disease that must be considered in order to understand it in full.
  1. Incidence
     • How much of the disease is present?
     • Where is the disease found?
     • In what species is the disease seen?
  2. Aetiology
     • Causal agent(s)
     • Predisposing factors
  3. Transmission
     • How is the disease spread between individuals?
     • Is the disease zoonotic?
  4. Pathogenesis
     • How the causal agent(s) exert their effect within the body.
  5. Diagnosis
     • History
     • Clinical findings
       • Clinical examination
       • Clinical pathology
     • Biopsy or post-mortem examination
  6. Prognosis and Treatment
  7. Control and Prevention
     • The ideal situation

Post-Mortem Examination

• Post-mortem examination (PME) investigates the observable structural changes in the animal.
• Information relating to the disease withing the body or specific tissue is gained from PME.
  • This includes information on the disease's
    • Aetiology (cause).
    • Pathogenesis (development).
• Several types of changes are encountered at post-mortem examination.
  1. Those due to the disease
     • Lesions
  2. Those occuring immediately prior to death
     • Agonal
  3. Those occuring after death
     • Post-mortem

Techniques Involved in Pathological Examination

• Fluid examination
  • E.g. blood, urine, discharges from orifices and so on.
• Cytology
  • Examination of cells in smears, aspirates and fluids.
• Necropsy
  • Visual examination of the gross changes in the dead body.
• Histopathology
  • Microscopic examination of:
    • Tissues selected from the dead body after necropsy.
    • Biopsy/excision materials from lesions in the living animal.
• Histochemistry
  • Microscopic visualisation of enzymatic activity in tissues.
• Immunological methods
  • Specific antibody activity can be detected in tissues and fluids.
    • Examination of serum can show prior exposure to a particular infectious agent (i.e. specifice antibodies).
  • Specific antigens can be detected in tissues.
    • When linked to a marking agent (e.g. a fluorescent dye), an antibody can localise its antigen in the tissue.
• Electronmicroscopy
  • Electronmicrosopcy shows fine detail of the surfaces or internal structures of cells.
• Bacteriology/ Virology/ Parasitology
  • These techniques allow the isolation and identification of pathogenic bacteria, viruses and parasites.
• Toxicology
  • Analysis of tissues for particular poisons and toxins.

Degenerations and Infiltrations

• Degenerations and infiltrations are the morphological manifestation of an altered metabolism within the cell.
  • A particular kind of change within a cell or tissue may suggest that a specific type of alteration has occurred.
• Degenerations and infiltrations are types of structural changes.
  • These are best considered at a cellular level.
  • These structural changes are deviations from the cell's normal structure and function.
    • Parameters are outside the normal physiological range for the cell.
• Degeneration
  • The tissue cell shows some change in itself.
• Infiltration
  • Something accumulates in the cell or tissue.

Cellular Swelling

this is the earliest detectable degenerative changes, and due to impairment of the integrity of the cell membrane. - this is the mildest form of cellular degeneration, and was first described about 100 years ago. It is the first stage in injury to a cell and may be caused by a variety of insults. Lack of oxygen - anoxia - to a tissue and toxic influences are common causes of cellular swelling. It is characterised by a moderate swelling of the individual cells, and is caused by an influx of water into the cell. The gross appearance of an organ diffusely affected with cloudy swelling is somewhat paler than normal, perhaps partly due to the swollen cells also encroaching upon the tissue's own blood vessels. Appreciable gross enlargement of the organ may be difficult to detect without cutting into it. Because each individual cell is increased in size, the entire volume of the organ is also increased, so that on cutting into the liver or kidney capsule, the cut ends may retract somewhat due to the bulging outwards of the underlying swollen parenchyma. The degree of swelling is not great and could be easily confused with early post-mortem changes in the organ.

Histologically, the individual cells appear somewhat swollen. In H&E stained sections, the cytoplasm appears redder in colour. A very important feature is that the nucleus is normal. It is best appreciated in the liver and kidney in damage caused by circulating toxins where the toxins are not powerful to actually kill the cells. Cellular swelling is an important stage in degeneration, but not particularly commonly observed on its own without more serious changes because it is also not easy to identify unless the post- mortem examination is performed very soon after the animal's death, as early post-mortem (autolytic) change in dead tissue looks rather similar. It is also reversible, that is when the toxin is no longer exerting its effect, the tissue returns to normal. It may also be a transient stage in the more serious forms of degenerations which follow.

Hydropic Degeneration

Hydropic degeneration - often indicates severe cellular damage due to viruses and is a more severe or advanced form of cellular swelling in which a. the cells may swell up like a balloon prior to their destruction, or b. there is a discrete bleb (vacuole) of fluid within the cytoplasm. a. the former is sometimes called 'ballooning degeneration' and may occur in a variety of conditions, but particularly viral conditions of epithelial tissue. The best example is 'Foot and Mouth Disease' where the virus attacks the stratum spinosum of the epithelium of the tongue and feet. The affected cells are ballooned up with water containing the replicating virus. The cells swell until they burst and the fluid they contain forms microvesicles (blisters) in this layer of the epithelium which may later burst, shedding vast quantities of the virus. When it bursts, the edges of the erosion look ragged, but within weeks the germinal epithelium at the base of the erosion regenerates the epithelium, leaving no trace of a scar.

b. in vacuolar degeneration, the second type, the excess water is transferred to the endoplasmic reticulum (ER) which swells and eventually fragments, leaving a fluid vacuole in the cytoplasm. It commonly occurs in cells such as the hepatocyte, renal tubular epithelium and pancreatic acinar cell which are very metabolically active and have welldeveloped pumping mechanisms.