Introduction to pathology. Methods of study of the pathological anatomy. Experimental methods in pathological physiology.
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Introduction to pathology
Pathology is the scientific study of disease. It explains:
- Etiology - cause of disease
- Pathogenesis - sequence of mechanisms by which disease develops
- Morphologic changes - structural alterations in cells, tissues, and organs
- Functional consequences and clinical manifestations - how these changes produce symptoms, signs, complications, and death
Pathology links the basic sciences to clinical medicine. Its two broad divisions are:
- General pathology: fundamental reactions of cells and tissues to injury, such as inflammation, degeneration, necrosis, circulatory disturbances, repair, and neoplasia.
- Systemic or special pathology: diseases as they affect particular organs or organ systems.
Pathological anatomy, also called anatomic pathology or cellular pathology, includes histopathology, cytopathology, autopsy examination, and molecular tissue diagnosis. Tissue assessment supports diagnosis, staging, prognosis, and therapeutic selection. Bailey and Love's Short Practice of Surgery, 28th ed., p. 199.
Methods of study in pathological anatomy
Pathological anatomy studies the structural changes caused by disease at gross, microscopic, ultrastructural, and molecular levels.
| Method | Material examined | Main use |
|---|---|---|
| Autopsy | Whole body and organs after death | Determines cause of death; assesses extent of disease; correlates clinical and pathological diagnoses |
| Biopsy | Tissue from a living patient | Establishes diagnosis before treatment; helps grade, stage, and guide treatment |
| Surgical pathology | Resected organ, tumour, or operative specimen | Examines margins, extent, nodal spread, and associated lesions |
| Cytology | Individual cells or small cell clusters | Screening and diagnosis, for example exfoliative cytology, body-fluid cytology, and fine-needle aspiration |
| Gross examination | Unprocessed tissue/organ | Assesses size, shape, colour, consistency, surface, cut section, and lesion distribution |
| Light microscopy | Thin stained tissue sections | Demonstrates cellular and tissue architecture |
| Special stains and histochemistry | Tissue sections | Identifies substances such as glycogen, mucin, iron, amyloid, collagen, and microorganisms |
| Immunohistochemistry | Tissue or cell preparations | Detects specific antigens using labelled antibodies; useful in tumour typing and identifying infectious agents |
| Electron microscopy | Ultrathin tissue sections | Shows ultrastructural abnormalities, especially in renal, muscle, metabolic, and some tumour disorders |
| Molecular pathology | DNA, RNA, proteins, or tissue | Detects mutations, translocations, gene amplification, and infectious genomes; helps classify disease and choose targeted therapy |
1. Autopsy
An autopsy is systematic examination of the body after death.
Types
- Clinical or pathological autopsy: evaluates disease, treatment effects, complications, and cause of death.
- Medicolegal or forensic autopsy: performed when death is sudden, suspicious, violent, unexplained, or legally significant.
Value
- Establishes immediate and underlying causes of death.
- Reveals unsuspected disease.
- Confirms or corrects clinical diagnoses.
- Contributes to education, audit, epidemiology, and research.
Limitations
- Postmortem changes may alter tissues.
- Terminal events may obscure the primary disease.
- Consent and legal requirements apply.
2. Biopsy
A biopsy is removal of tissue from a living person for pathological examination.
Common forms
- Incisional biopsy: a representative portion of a lesion.
- Excisional biopsy: removal of the entire lesion.
- Needle-core biopsy: cylindrical tissue cores.
- Endoscopic biopsy: tissue from gastrointestinal, respiratory, or urinary tracts.
- Punch biopsy: often used in skin lesions.
- Curettage biopsy: scraping of tissue, such as endometrium.
- Frozen section: rapid intraoperative examination of fresh tissue.
A correctly taken, adequately fixed, representative specimen is essential. Biopsy analysis often provides diagnosis and information on disease severity, prognosis, tumour grade, stage, margins, and biomarkers. Histopathology, cytopathology, autopsy work, and molecular tissue diagnosis are core components of cellular pathology. Bailey and Love's Short Practice of Surgery, 28th ed., p. 199.
3. Histopathology
Tissue is generally processed through these steps:
- Fixation, commonly in formalin, to preserve tissue structure
- Grossing and selection of representative areas
- Dehydration and embedding in paraffin wax
- Cutting thin sections with a microtome
- Staining, usually with haematoxylin and eosin (H&E)
- Microscopic interpretation
H&E staining shows nuclei blue-purple and cytoplasm/extracellular components in shades of pink, allowing recognition of tissue architecture, inflammation, cell injury, necrosis, fibrosis, and tumours.
4. Cytopathology
Cytology examines individual cells rather than the full tissue architecture.
Examples
- Cervical smear cytology
- Sputum cytology
- Urine cytology
- Pleural, peritoneal, and cerebrospinal-fluid cytology
- Fine-needle aspiration cytology of lymph node, thyroid, breast, or mass lesions
It is relatively rapid and minimally invasive, but sometimes must be supplemented by biopsy because tissue architecture may be needed for a definitive diagnosis.
Experimental methods in pathological physiology
Pathological physiology studies disturbed function in disease. It asks: How does a structural lesion alter function, and how does this generate clinical manifestations?
Experimental methods reproduce, observe, and modify disease processes under controlled conditions.
Main experimental approaches
| Method | Principle and examples |
|---|---|
| Animal models | Disease is induced or studied in animals, for example experimental hypertension, diabetes, inflammation, renal injury, tumours, or infection |
| Genetically modified models | Gene knockout, knock-in, transgenic, or conditional models clarify the role of particular genes |
| Cell culture | Cells are exposed to toxins, hypoxia, pathogens, cytokines, or drugs to study cellular injury and responses |
| Organoid and tissue culture | Three-dimensional tissues or organ-like systems model disease more closely than isolated cells |
| Isolated organ or tissue preparations | Perfused heart, isolated vessel, skeletal muscle, or intestinal tissue enables controlled measurement of organ function |
| In vivo functional experiments | Measurement of blood pressure, cardiac output, respiration, renal filtration, nerve activity, metabolism, or behaviour in living models |
| Induced disease models | Physical, chemical, biological, immunological, nutritional, endocrine, or surgical interventions reproduce selected disease mechanisms |
| Comparative and control studies | Experimental and control groups are compared to establish causal relationships |
| Interventional studies | Removing a suspected cause, blocking a pathway, replacing a deficient factor, or administering a treatment tests the mechanism |
Ways experimental disease may be produced
- Physical factors: trauma, heat, cold, radiation, pressure, hypoxia.
- Chemical factors: toxins, drugs, carcinogens, acids, alkalis.
- Biological factors: bacteria, viruses, fungi, parasites, or their toxins.
- Nutritional factors: vitamin deficiency, protein deficiency, high-fat diet, caloric excess.
- Immunological factors: induction of hypersensitivity, autoimmunity, or immune deficiency.
- Surgical methods: vessel ligation, organ removal, obstruction, transplantation, or denervation.
- Genetic manipulation: alteration of genes to model inherited disorders or identify molecular mechanisms.
General stages of an experiment
- Define a clear hypothesis.
- Choose an appropriate model that resembles the human disease.
- Include suitable controls and, where appropriate, randomization and blinding.
- Induce or observe the pathological process.
- Measure functional, biochemical, morphological, and molecular outcomes.
- Analyze whether the intervention or variable caused the observed change.
- Confirm findings in additional models or human tissue when possible.
Strengths and limitations
Strengths
- Enables controlled testing of cause-and-effect relationships.
- Helps identify mechanisms before human trials are feasible.
- Permits testing of prevention and treatment strategies.
Limitations
- An experimental model may reproduce only part of a human disease.
- Species differences can limit translation to patients.
- Artificially induced disease may differ from naturally occurring disease.
- Ethical requirements require replacement, reduction, and refinement of animal use, alongside appropriate consent and oversight for human-derived specimens.
Key point: Pathological anatomy primarily identifies what structural changes occur, whereas pathological physiology explains how those changes disturb function and produce disease.
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