Basic Pathology Introduction

Introduction to Pathology

• Definition of Pathology: the study of diseases by scientific methods
• Pathology is literally the study (logos) of suffering (pathos)
• The ultimate goal of pathology is the identification of the causes of disease, leading to disease treatment and prevention

History of Pathology

• Prehistoric time to AD1500: religious beliefs and magic to rational approach
• Key figures: Hippocrates, Galen, Avicenna, Al-Razi, and Al-Zahrawy
• AD1500-1800: Human Anatomy to Era of Gross Pathology
  • Renaissance: Leonardo da Vinci, Vesalius, and Fallopius
  • Leeuwenhoek, Malpighi, and Morgagni
• 1800-1950: Technology Development & Cellular Pathology
  • Louis Pasteur, Hansen, Ehrlich, and Gram
  • Romanowsky, Koch, and May-Grunwald
• Rudolf Virchow: father of modern pathology, stated the cellular pathology concept

Virchow's Hypothesis

• Diseases can be defined by observing morphologic changes in cells
• Implication: diseases can be understood by studying cellular changes

Normal Homeostasis

• The body maintains a steady state (homeostasis) through continuous monitoring and adaptations
• Normal homeostasis is achieved by genetic programs, metabolism, proliferation, and differentiation

Pathology

• Pathology is the study of diseases by scientific methods
• Pathology is dynamic, with new findings constantly changing and expanding our understanding of diseases
• In medicine, diseases are studied under the following headings:
  • Definition
  • Epidemiology
  • Etiology (Why?)
  • Pathogenesis (How?)
  • Morphology (What?)
  • Clinical features/presentation
  • Investigations
  • Treatment and management
  • Prognosis

Classification of Pathology

• According to range of study: General (Basic) Pathology and Systemic (Specific) Pathology
• According to uses and practice field: Experimental Pathology, Clinical (Diagnostic) Pathology

Methods Used in Pathology

• Morphologic: Gross observation, Microscopic examination (histo & cyto pathology)
• Molecular/Biochemical/Cytogenetic: Applied clinical and research methods
• Immunologic/Serologic: Serum, plasma, cell suspensions, tissues
• Microbiologic: Cultures, biochemical assays, immunologic

Branches/Subdivisions of Pathology

• Histopathology: study of tissue biopsied/excised from the body to diagnose diseases
• Cytopathology: study of cell morphology, exfoliated or aspirated from the body to diagnose diseases
• Immunohistochemistry: special staining procedure to detect special antigens in the tissue
• Hematology: study of blood, blood cells, and bone marrow
• Chemical pathology/Clinical biochemistry: study and diagnosis of disease from chemical changes in tissues and fluids
• Microbiology: study of infectious diseases and diagnosis of causative organisms
• Immunology: study and analysis of the immune system of the body
• Toxicology: study of various poisonous and toxic substances
• Cytogenetics (Clinical Genetics): study of chromosomes and genes abnormalities
• Molecular Pathology: e.g. fluorescent in situ hybridization, Southern blot tests
• Autopsy (Forensic Pathology): sub-specialty of pathology that involves examining a dead body

Importance of Pathology

• Pathology is an essential part of medical education and practice
• Pathology gives clinical purpose to basic sciences and scientific research
• Pathology provides diagnostic services for all other medical specialties
• "As is our pathology, so is our practice." - Sir William Osler

Adaptations and Accumulations

• Cellular Responses: Cells respond to modest changes (stress and injuries) by functional and structural adaptations.
• Types of Adaptations:
  • Hypertrophy: Increase in size of cells or organs due to increased demand or stimulation.
  • Hyperplasia: Increase in the number of cells in an organ or tissue due to increased demand or stimulation.
  • Atrophy: Decrease in size of cells, tissues, or organs due to decreased demand or stimulation.
  • Metaplasia: Reversible change in which one mature cell type is replaced by another mature cell type, better able to withstand a chronic adverse environment.

Hypertrophy

• Physiologic Hypertrophy: Appropriate cellular proliferation to maintain normal function, e.g., lactating breast, uterus in pregnancy.
• Pathologic Hypertrophy: Inappropriate cellular proliferation, e.g., cardiac concentric left ventricular hypertrophy due to chronic hemodynamic overload.
• Mechanism: Increased cell size due to synthesis of more structural components, especially intracellular proteins.

Hyperplasia

• Physiologic Hyperplasia: Appropriate cellular proliferation to maintain normal function, e.g., breast hyperplasia in pregnancy, compensatory hyperplasia in liver.
• Pathologic Hyperplasia: Inappropriate cellular proliferation, e.g., endometrial simple hyperplasia, endometrial complex hyperplasia with atypia.
• Mechanism: Increased number of cells due to excessive hormonal stimulation or growth factor action.

Atrophy

• Physiologic Atrophy: Decrease in size of cells, tissues, or organs due to decreased demand or stimulation, e.g., loss of hormone stimulation in menopause.
• Pathologic Atrophy: Decrease in size of cells, tissues, or organs due to disease or injury, e.g., disuse, denervation, ischemia, pressure.
• Mechanism: Combination of decreased protein synthesis and increased protein degradation, and increased autophagy.

Metaplasia

• Definition: Reversible change in which one mature cell type is replaced by another mature cell type, better able to withstand a chronic adverse environment.
• Types of Metaplasia:
  • Epithelial Metaplasia: e.g., squamous metaplasia in respiratory epithelium, intestinal columnar metaplasia in esophagus.
  • Mesenchymal Metaplasia: e.g., osseous metaplasia, chondroid metaplasia, myeloid metaplasia.
• Mechanism: Reprogramming of stem cells in basal layer of epithelium or of pluripotent mesenchymal cells in connective tissue, causing them to differentiate along a new pathway.

Clinical Significance

• Metaplasia: Can lead to functional deficits, dysplastic changes, and progression to cancer in metaplastic epithelium.
• Adaptations: Can be reversible, but persistent stimuli can lead to malignant transformation.