Human Disease and Pathology Quiz

Principles of Pathology Module MOD002800

• The module is titled Principles of Pathology, Module MOD002800
• The lecturer is Dr Joseph Bird
• Contact email: [email protected]
• Student ID: SCI009

Origins of Pathology

• Medicine relies on the examination of diseases to promote health
• Pathology is the study of suffering (pathos)
• The study of logos (study of) combined with the suffering (pathos) constitutes the study of pathology
• Plutarch (c. 46-120), a Greek biographer and essayist, is connected to this concept.

Understanding Pathology

• Pathology involves functional and structural changes in disease from molecular to organism level
• The goal of pathology is to identify the causes of disease

The History of Pathology

• Key historical periods in the understanding of pathology include:
  • Animism, associating disease with supernatural forces.
  • Humours, believing disease stemmed from an imbalance of bodily fluids.
  • Spontaneous Generation (Abiogenesis), proposing living things arose from non-living matter.
  • Modern and Molecular Pathology (evidence-based), a more advanced approach to understanding disease

Animism

• Primitive system of understanding disease attributed it to adverse influences of immaterial or supernatural forces.
• No advancements could be derived from studying the dead.
• Plato and Pythagoras were associated with this system.

Humours

• Hippocrates and Empedocles (500 B.C. to 1500 A.D.) associated disease with imbalances of bodily fluids (humours).
• Four types of humours, illustrated in a graphic diagram, each related to different elements and states (wet/dry, hot/cold).

Spontaneous Generation or Abiogenesis

• Up until 1800 AD, spontaneous generation, supported by individuals like Johannes Baptista von Helmont, was a concept believed by many.
• Francisco Redi, Lazzaro Spallanzani, and Louis Pasteur later debunked this theory.
• Disease was perceived as arising through metamorphosis independent of external or other influences.

Modern and Molecular Pathology

• Rudolf Carl Virchow is considered the "Father of Modern Pathology."
• Giovanni Morgagni is linked to modern autopsy procedures.

Two Stages of Pathology

• General pathology studies the overarching mechanisms of diseases like inflammation, tumors, and degenerations
• Systematic pathology analyzes specific diseases impacting individual organs or systems, examples include appendicitis, lung cancer, and atheroma

The Language of Pathology

• Relevant terms to define a disease process include:
  • epidemiology,
  • etiology,
  • pathogenesis,
  • risk factors,
  • predisposition,
  • complications and sequelae,
  • prognosis, and
  • treatment. These can be considered "testable" terms.

Some useful definitions

• Predisposition: A susceptibility to disease which, given certain circumstances, may manifest as clinically evident disease.
• Risk factor: A factor linked to a higher probability of developing a particular disease.
• Aetiology: The cause of a disease,
• Pathogenesis: The pathological pathway resulting in clinically evident disease

Patterns of human disease

• Disease patterns differ greatly and are influenced by these factors:
  • Environmental factors like diet, climate, and wealth.
  • Genetic factors within the population
  • Natural bodily variability in response to disease.
• The examples of USA & Kenya were presented in a graph

How do we define disease?

• Disease is the result of injury, external and internal factors cause it.
  • Adverse environment (external)
  • Genetic abnormality (internal)
  • A combination of both.
• Homeostasis is the body’s ability to regulate itself to mild environmental changes. Disease is considered a consequence when this homeostasis is disrupted

Classification of external and internal factors in disease

• A table classifies external and internal factors contributing to diseases:

  • External factors include:
    • Physical trauma (e.g., bone fracture)
    • Radiation (e.g., cancer)
    • Extreme temperatures (e.g., frostbite)
    • Toxic substances (e.g., tobacco lung damage)
    • Infectious agents (bacteria, viruses, fungi, parasites)
  • Internal factors include:
    • Genetics (e.g., sickle cell disease, cystic fibrosis)
    • Metabolic disorders (e.g., diabetes)
    • Cellular issues (e.g., autoimmune diseases)
    • Structural defects (e.g., spina bifida)
    • Acquired conditions (e.g., biliary tract obstruction).

The Disease Process

• Disease is represented as an interconnected network, like the London Underground.
• Interconnected network pathways of disease processes are identified: inflammation, repair, and healing.
• Sub-components are shown, such as Ischemia or Fibrosis.
• Key aspects like Cytolisis, Karyolysis, and Death represent the conclusion of processes.
• Disease is influenced by external and internal factors, producing symptoms and signs.
• A specific example given is Streptococcus pneumoniae causing lung consolidation leading to symptoms such as cough and breathlessness.

Physical Injury

• Includes obvious cellular traumas such as mechanical injuries, cuts, scrapes, broken bones and bruises.
• Intact skin and mucus membranes normally provide a defense against infection, unless compromised by physical injury.
• Other types such as heat, cold, and irradiation can also cause injury.
• Injury to tissues due to physical injury can expose cells to other harmful agents.

Chemical Injury

• Three main forms of chemical injury are outlined:
  • Direct injury: Cellular toxins directly cause cell damage, even at low concentrations.
  • Cooperative injury: Less toxic chemicals become damaging following reactions within the body.
  • Injury due to quantitative variations: Normally vital chemicals become harmful if present in excess.
• The figure shows two faces of a former Ukrainian President, Viktor Yushchenko.

Living organisms which cause disease

• Pathogenic organisms pose a unique threat unlike physical or chemical injury as they can multiply.
• Bacteria: cause disease through secretion of harmful molecules, exotoxins or endotoxins.
• Viruses: exclusively multiply inside living cells, resulting in various diseases from mild (common cold) to severe (HIV/AIDS)
• Parasites: are unicellular (e.g., malaria) or multicellular (e.g., roundworms).

Genetic factors influence nearly all diseases

• Inherited disorders are due to defective or missing genes (e.g. cystic fibrosis); these may present from birth or later in life.
• Somatic mutations occur during a person's life, altering genetic material within their cells.
• Examples of genetic changes are presented (cells such as normal and abnormal cells, dominant oncogene.)

Looking beyond the cell...

• Some tissues are more vulnerable to injury than others.
• Organotropism refers to an agent's specific effect on a particular organ
• The occurrence of injury can depend on chance or cell vulnerability.
• Injury to cells can lead to secondary damage to adjacent cells.
• Inflammation and immune responses can also cause damage.
• Agents can impact the tissue matrix, causing injury by targeting connective tissue proteins such as collagen and elastin instead of cells, or by using enzymes such as hyaluronidase to disrupt the tissue framework.

Biochemical changes in cells after injury

• Two key questions are posed about biochemical changes within injured cells and the difference between reversible and irreversible damage.
• Four key sites are essential for cell damage: plasma membrane, mitochondria, ionic channels in cell membranes and cytoskeleton.

Biochemical changes in cells after injury (continued)

• Reversible and irreversible changes in cells after injury are highlighted.
• Reversible changes include cell swelling, mitochondrial swelling, endoplasmic reticulum (ER) swelling, detachment of ribosomes, loss of microvilli, surface blebbing, clumping of nuclear chromatin, and lipid deposition
• Irreversible results in the release of lysosomal enzymes, membrane disruption, leakage of cell enzymes and proteins, and nuclear changes such as pyknosis and karyolysis
• Myocardial infarction (heart attack) cellular changes are discussed

The (Medical) Nature of Pathology

• Surgical pathology involves examining tissue sections using light and electron microscopy, along with immunohistochemistry and molecular techniques (DNA, RNA).
• Cytopathology focuses on the examination of individual cells (such as in a Pap smear) in body fluids or smears/scrapes.
• Morbid anatomy (or autopsy) is employed to uncover the cause of death and associated disease processes.

Techniques of Pathology

• Various techniques are utilized in pathology, including:
  • Gross pathology (e.g., morbid anatomy)
  • Light microscopy
  • Histochemistry
  • Immunohistochemistry and immunofluorescence
  • Electron microscopy,
  • Biochemistry (e.g. serum assays),
  • Hematological techniques (e.g., RBC count),
  • Cell culture,
  • Medical microbiology (e.g., culture of isolated body fluids), and
  • Molecular pathology (e.g. FISH, DNA microarray)

Light Microscopy and Immunohistochemistry

• Hematoxylin stains negative and negatively charged nucleic acids appear blue
• Proteins are stained brown with antibodies specific to the interested target.

Molecular Pathology

• Fluorescence in situ hybridization (FISH) is a microscopy technique

Cytopathology

• Pap smears aid in evaluating cervical abnormalities, detecting changes in cellular structure and the presence of inflammatory cells.

Subdivisions of Clinical Pathology

• Various specialized areas within clinical pathology cover different disease aspects:
  • Histopathology: Examining tissue for diseases
  • Cytopathology: Examining cells in body fluids or smears.
  • Hematology: Studying blood disorders.
  • Microbiology: Studying infectious diseases.
  • Immunology: Examining immune system functions.
  • Chemical pathology: Analyzing chemical changes in tissues.
  • Genetics: Studying chromosome and gene abnormalities.
  • Toxicology: Analyzing the effects of poisons,
  • Forensic pathology: Performing autopsies, when death under suspicious circumstances.

Summary,

• A summary of the module on Pathology is included
• Subheadings include origins, history, stages, language, definition, classification, and techniques

Recommended Reading

• Books on Biology of Disease (ISBN 978-0-7487-7210-0)
• Muir's Textbook of Pathology (ISBN 978-1-4441-8497-6)
• Robbins Basic Pathology (ISBN 978-1-4377-1781-5)
• Wheater's Basic Pathology (ISBN 978-0-443-06797-6).