General Pathology - Intro to Pathology Notes

General Pathology (SAHS 206)

Emmanuel Akomanin Asiamah BSc, PGDip (ICM-UK), MSc. (UK), FWAPCMLS Lecturer/Consultant Medical Lab Scientist University of Health and Allied Sciences / Ho Teaching Hospital, Ghana

Introduction to General Pathology

Understanding the Foundations of Disease

What is Pathology?

• Study of disease.
• Explores causes, mechanisms, and effects of diseases.
• Links basic science with clinical practice.

Relevance to Medical Laboratory Scientists

Plays a key role in the investigative and diagnostic work of the MLS, which includes analyzing:

• Tissue samples.
• Bodily fluids (blood, urine, CSF).
• Microbial cultures.
• Molecular markers.

Key Roles of MLS in Pathology

• Diagnostic Testing: Analyze samples to detect abnormalities.
• Monitoring Disease Progression: Track changes over time.
• Supporting Treatment Decisions: Provide data for targeted therapy.
• Research and Quality Control: Ensure accuracy and reliability of lab results.
• Disease Surveillance: For public health and epidemiological studies.

Branches of Pathology

• General vs. Systemic Pathology
• Anatomical Pathology
• Clinical Pathology
• Forensic Pathology
• Molecular Pathology

Why Pathology Matters in Medical Laboratory Science?

• Disease Diagnosis:
  • Histopathology, cytology, hematology, microbiology, and molecular diagnostics all depend on pathological principles.
  • Example: Identifying cancer cells in a Pap smear requires knowledge of cellular changes in dysplasia and malignancy.
• Interpreting Test Results:
  • Understanding the pathophysiology behind abnormal test values helps in accurate interpretation.
  • Example: Elevated liver enzymes may indicate hepatocellular damage due to hepatitis or drug toxicity.
• Precision Medicine:
  • Modern diagnostics increasingly rely on molecular pathology (e.g., genetic mutations in cancer and infectious diseases).
• Quality Assurance:
  • A strong foundation in pathology ensures that laboratory scientists recognize artifacts vs. real pathology and maintain high diagnostic standards.

Expectations from Studying General Pathology

As a Medical Laboratory Scientist, studying general pathology will equip you with:

• Understanding Disease Mechanisms
• Recognizing Morphological Changes
• Correlating Lab Findings with Disease States
• Knowledge of Common Diseases
• Skills in Laboratory Diagnostics

Objectives

By the end of this course, you should be able to:

• Define pathology and explain its role in understanding human disease.
• Differentiate between the main branches of pathology (e.g., general vs. systemic, anatomical vs. clinical).
• Describe the fundamental causes and mechanisms of disease, including genetic and acquired etiologies.
• Identify cellular adaptations to stress (e.g., hypertrophy, atrophy, metaplasia) and distinguish between reversible and irreversible injury.
• Differentiate between necrosis and apoptosis and recognize their key morphological and molecular features.
• Describe the phases and outcomes of inflammation, including acute and chronic responses.
• Explain the processes of tissue repair and wound healing, and list factors that influence healing.
• Recognize basic hemodynamic disorders such as edema, thrombosis, embolism, infarction, and shock.
• Understand the concepts of neoplasia, including tumor classification, behavior, and mechanisms of carcinogenesis.
• Outline the basic principles of immune pathology, including hypersensitivity, autoimmunity, and immunodeficiency.

Basic Disease Concepts

• Disease: Abnormal condition with specific signs and symptoms.
• Etiology: Underlying cause of disease.
• Pathogenesis: Mechanism of development.
• Pathognomonic (pathognomic): A characteristic sign/feature for diagnosis or identification.

Causes of Disease

• Genetic: Inherited mutations, chromosomal abnormalities.
• Acquired: Infections, trauma, toxins.
• Idiopathic: Unknown causes.
• Multifactorial: Combination of factors.

Natural History of Disease

• Importance in prognosis and treatment
• Stages:
  • Susceptibility
  • Subclinical Disease (Pre-symptomatic)
  • Clinical Disease (Symptomatic Phase)
  • Clinical Outcome (Recovery, Chronicity Disability, or Death)

Examples of Natural History

• Infectious Disease (e.g., Hepatitis B):
  • Exposure → Asymptomatic infection → Acute illness → Recovery (90%) or Chronic infection → Cirrhosis/Liver cancer.
• Chronic Disease (e.g., Type 2 Diabetes):
  • Insulin resistance → Prediabetes → Early diabetes (asymptomatic) → Symptomatic hyperglycemia → Complications (neuropathy, nephropathy).
• Cancer (e.g., Colorectal Cancer):
  • Normal mucosa → Adenoma (polyp) → Early carcinoma → Metastatic disease.

Overview of Cellular Adaptations

• Adaptations occur in response to stress
• Maintain homeostasis and function

Types of Cellular Adaptation

• Hypertrophy: Increase in cell size.
• Hyperplasia: Increase in cell number.
• Atrophy: Decrease in size or function.
• Metaplasia: Change from one cell type to another.

Physiologic vs. Pathologic Cellular Adaptations

Reversible vs. Irreversible Injury

• Reversible: Cellular swelling, fatty change.
• Irreversible: Membrane damage, mitochondrial dysfunction, cell death.

Cellular Swelling and Fatty Change

• Common in hypoxia and toxic injury.
• Liver and kidney often affected
  • Liver: normal
  • Kidney: normal
  • Kidney: Cloudy Swelling
  • Liver: Fatty Change

Mechanisms of Cell Injury

• ATP depletion
• ROS production
• Calcium influx
• Membrane permeability disruption

Cell Death Pathways

• Necrosis: Uncontrolled, inflammation-causing.
• Apoptosis: Programmed, no inflammation.

Types of Necrosis

• Coagulative: Most organs
• Liquefactive: Brain, abscess
• Caseous: TB
• Fat: Pancreas
• Fibrinoid: Vessels
• Gangrenous: Limbs

Morphological Features of Necrosis

• Cytoplasmic changes: Eosinophilia, Vacuolation, Calcification
• Nuclear changes: Pyknosis, Karyorrhexis, Karyolysis

Apoptosis Pathways

• Intrinsic: Mitochondria-mediated, Bcl-2 family
• Extrinsic: Death receptors (Fas, TNF)
• Caspase activation cascade

Inflammation Overview

• Cellular response to eliminate cause of injury
• Acute vs. Chronic

Acute Inflammation

• Vascular changes: Vasodilation, permeability
• Cellular events: Neutrophil migration, phagocytosis

Chemical Mediators of Inflammation

• Histamine, prostaglandins, cytokines
• Complement system
• Source and function of each

Outcomes of Acute Inflammation

• Resolution
• Abscess formation
• Chronic inflammation
• Scarring

Chronic Inflammation

• Causes: Persistent infections, autoimmune disease
• Infiltration with lymphocytes and macrophages
• Tissue destruction and fibrosis

Granulomatous Inflammation

• Collection of macrophages (epithelioid cells)
• With or without caseation
• Seen in TB, sarcoidosis, leprosy

Regeneration vs. Repair

• Regeneration: Replacement by identical cells
• Repair: Fibrosis, scar formation

Role of Stem Cells

• Pluripotent and tissue-specific
• Regenerative potential

Phases of Wound Healing

• Inflammatory phase
• Proliferative phase
• Remodeling phase

First vs. Second Intention

• First: Clean, minimal damage
• Second: Larger wounds, more granulation and scar

Factors Affecting Healing

• Local: Infection, blood supply
• Systemic: Nutrition, diabetes, age

Complications of Healing

• Keloid
• Contracture
• Dehiscence
• Ulceration

Hemostasis Overview

• Normal process to stop bleeding
• Involves platelets, coagulation cascade, endothelium

Edema

• Accumulation of fluid in tissues
• Causes: Increased hydrostatic pressure, decreased oncotic pressure, lymphatic obstruction

Hyperemia vs. Congestion

• Hyperemia: Active, increased blood flow
• Congestion: Passive, impaired outflow

Hemorrhage

• Types: Petechiae, purpura, ecchymosis, hematoma
• Causes: Trauma, platelet disorders, clotting defects

Thrombosis and Virchow's Triad

• Endothelial injury
• Stasis or turbulence of blood flow
• Hypercoagulability

Embolism

• Types: Pulmonary, systemic, fat, air, amniotic
• Consequences depend on location and size

Infarction

• Ischemic necrosis due to obstruction
• Red vs. white infarcts

Shock

• Hypovolemic, cardiogenic, septic
• Stages: Initial, progressive, irreversible

Growth Disorders

• Hyperplasia
• Hypertrophy
• Atrophy
• Dysplasia
• Neoplasia

Benign vs. Malignant Tumors

• Benign: Localized, slow-growing, well-differentiated
• Malignant: Invasive, fast-growing, poorly-differentiated

Tumour Nomenclature

• Benign: -oma (e.g., lipoma)
• Malignant: carcinoma, sarcoma

Cancer Cell Characteristics

• Autonomy, evasion of apoptosis, angiogenesis
• Invasion and metastasis

Carcinogenesis

• Initiation, promotion, tumor progression
• Oncogenes, tumor suppressors

Tumour Spread

• Local invasion
• Lymphatic and hematogenous metastasis
• Seeding of body cavities

Grading and Staging

• Grading: Degree of differentiation
• Staging: TNM system (size, nodes, metastasis)

Immune Mechanisms

• Innate vs. Adaptive
• Humoral and Cell-mediated immunity

Hypersensitivity Reactions

• Type I: Allergy
• Type II: Cytotoxic
• Type III: Immune complex
• Type IV: Delayed

Autoimmune Diseases

• Systemic: SLE, RA
• Organ-specific: Type 1 DM, Hashimoto thyroiditis

Immunodeficiency

• Primary: Genetic defects
• Secondary: HIV, malnutrition, drugs

Summary

• Cell Injury and Adaptation
• Inflammation and Repair
• Circulatory Disorders
• Neoplasia and Immune Pathology